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A Gause

Publications and source records attributed to A Gause.

At least 73 records · Page 4Linked to original sources
PubMed1992

Soluble CD8, CD25 and CD30 antigens as prognostic markers in patients with untreated Hodgkin's lymphoma.

In a search for serum markers with prognostic value and specificity for disease activity in Hodgkin's lymphoma, we evaluated the clinical significance of soluble suppressor/cytotoxic T-cell antigen (sCD8), soluble interleukin-2 receptor (sCD25) and soluble Hodgkin's associated antigen (sCD30) levels in the serum of 90 patients with untreated Hodgkin's lymphoma (HD). HD patients in advanced stages had significantly higher sCD8 and sCD25 levels than normal controls. The rate of detectable sCD30, which was absent in healthy controls, depended on stage and histological subtype, and was 22% for the entire group. Low sCD25 levels (< 1000 U/ml) predicted an excellent prognosis (100% event-free survival), while patients with high sCD8 levels (> 750 U/ml) or the demonstration of sCD30 had a poor outcome. Therefore, all three markers have prognostic significance. However, only sCD30 correlated strictly with disease activity and seems to be of value for the follow-up of patients in remission.

Adolescent↗
PubMed1992

A somatically mutated V kappa IV gene encoding a human rheumatoid factor light chain.

The light chain of an IgA kappa rheumatoid factor (RF) produced by a hybridoma derived from a patient with rheumatoid arthritis (RA) has been shown to belong to the V kappa IV family. This RF light chain has 31 nucleotide differences compared with the single V kappa IV germline gene reported for the human genome. The patient's V kappa IV germline gene was sequenced, using the polymerase chain reaction (PCR), and shown to be identical to that previously reported. This demonstrates that the RF light chain is the product of a somatically mutated gene. A comparison with other known V kappa IV sequences shows that the RF light chain has more replacement mutations than most of the known V kappa IV light chains.

Amino Acid Sequence↗
PubMed1992

The clinical significance of cytokines and soluble forms of membrane-derived activation antigens in the serum of patients with Hodgkin's disease.

In a search for specific serum markers with prognostic impact in Hodgkin's Disease (HD), we evaluated the clinical significance of several cytokines (IL-1 beta, IL-2, IL-3, IL-6, G-CSF, GM-CSF, TNF-alpha) and soluble forms of membrane-derived antigens (sCD4, sCD8, sCD23, sCD25, sCD30) in the serum of patients with untreated HD. Elevations of three groups of serum factors were observed: Firstly, elevations of the hematopoietic cytokines GM-CSF (detected in 39%), IL-6 (57%) and IL-3 (13%), which occurred simultaneously in the majority of the cases; secondly, simultaneous elevations of the inflammatory cytokines TNF-alpha and IL-1 beta (detected in 7%); and finally, elevations of membrane-derived activation antigens sCD8, sCD25, and sCD30. While the cytokine levels did not correlate with other obvious parameters, the membrane-derived activation antigens sCD8, sCD25 and sCD30 were associated with a poor prognosis. Only sCD30 correlated with disease activity and holds promise for the follow-up of patients in remission. Further investigations of these parameters at the cellular level might help to elucidate the enigmatic biology of HD.

Antigens, CD↗
PubMed1992

Increased levels of circulating cytokines in patients with untreated Hodgkin's disease.

Expression of several cytokines has been demonstrated in Hodgkin and Reed-Sternberg (H&RS) cells in vitro and in vivo. In order to determine whether interleukin-1 beta (IL-1 beta), IL-3, IL-6, GM-CSF, G-CSF, and TNF-alpha are elevated in Hodgkin's disease (HD), we tested the sera of untreated patients with HD by means of sensitive sandwich ELISAs. GM-CSF was detected in 22/56 patients (39%; range 40-140 pg/ml), IL-3 in 5/40 (13%; range 13-26 pg/ml), and IL-6 in 32/56 patients (57%; range 12-332 pg/ml). TNF-alpha and IL-1 beta were detected in only 3/43 patients (7%; range: TNF-alpha: 36-66 pg/ml; IL-1 beta: 389-1505 pg/ml) and G-CSF not at all. All patients with measurable IL-3 levels had both elevated IL-6 and GM-CSF levels, and the majority of patients with elevated IL-6 also had elevated GM-CSF levels and vice versa. In contrast, the 3/40 patients with both measurable IL-beta and TNF-alpha did not have elevated IL-3, IL-6, or GM-CSF levels. Cytokine levels were independent of stage or the presence of B-symptoms, and there was no correlation with any other clinical or laboratory parameter. Elevations of the respective cytokines might be a means to maintain normal blood cell counts in the respective patients with HD.

Adolescent↗
PubMed1991

Clinical significance of soluble CD30 antigen in the sera of patients with untreated Hodgkin's disease.

The soluble form of the CD30 antigen (sCD30), an 88-kd glycoprotein that is released by Hodgkin's-derived cell lines in vitro, can be detected in patients with Hodgkin's lymphoma, adult (HTLV-1+) T-cell leukemia, rare cases of non-Hodgkin's lymphoma, and acute infectious mononucleosis (anti-EBV-IgM+). In a prospective study of 90 consecutive untreated patients with newly diagnosed Hodgkin's disease who were treated according to the protocols of the German Hodgkin Study group, 22% had detectable levels of sCD30 in their serum. sCD30 was only detected in patients with B symptoms (20 of 44 or 45%), and maximum sCD30 levels (88 U/mL) were found in stage IVB. Of 87 patients evaluable for response, sCD30+ patients had significantly lower rates of complete remission (9 of 20 or 45% v 60 of 67 or 90%; P less than .001) and higher rates of progressive disease (9 of 20 or 45% v 6 of 67 or 9%; P less than .001) than CD30+ patients. Similarly, freedom from treatment failure curves were significantly worse for CD30+ patients (P = .0003). sCD30 disappeared after successful treatment, but increased in patients with progressive disease. It was never detected in patients in complete remission or in healthy controls. We conclude that sCD30 is a valuable marker for disease activity and has prognostic significance in Hodgkin's disease.

Adolescent↗
PubMed1991

Low serum interleukin-2 receptor levels correlate with a good prognosis in patients with Hodgkin's lymphoma.

In order to evaluate the clinical significance of soluble interleukin-2 receptor (sIL-2R) levels in the serum of patients with Hodgkin's disease (HD), we tested the pretreatment sera of 82 patients. The HD patients had significantly higher sIL-2R levels than normal controls (4787 U/ml versus 290 U/ml; P less than 0.001). In patients presenting with B-symptoms, the median sIL-2R levels were significantly higher than in patients without B-symptoms (7978 versus 2128 U/ml; P less than 0.01). Patients in stage IVB had the highest sIL-2R levels (10,450 U/ml). Of 77 patients evaluable for response, all patients with sIL-2R levels less than 1000 U/ml achieved complete remission and no relapses occurred in this group after a median of 20 months. The fact that sIL-2R levels dropped after therapy, even in patients who suffered from progressive disease, suggests that Hodgkin and Reed-Sternberg cells are only a minor source of sIL-2R in HD. Therefore sIL-2R levels are of limited value as a marker of disease activity. However, pretreatment sIL-2R levels less than 1000 U/ml define a subgroup of adult HD patients with an excellent prognosis, and this fact might be helpful for the design of more custom-tailored therapy programs.

Adolescent↗
PubMed1991

B cells of chronic lymphatic leukemia express V genes in unmutated form.

In order to investigate whether the leukemic B cells in B-CLL express immunoglobulin genes in mutated or unmutated form, independent cDNA clones of one patient with B-CLL expressing heavy and light chain V region genes were sequenced. The sequences of both the VH and V kappa clones were identical. The V genes could be assigned to known germline V genes. No somatic mutations were found. At the V kappa-J kappa border there is an insertion of N-sequences which are only rarely found in immunoglobulin light chain genes. Our study confirms other published data on V gene expression in B-CLL in that the surface immunoglobulins in these tumors are unmutated.

Antigens, Differentiation↗
PubMed1991

The clinical significance of serum CD8 antigen levels in adult patients with Hodgkin's disease.

Increased suppressor T-cell activity has been observed in patients with Hodgkin's disease. In order to evaluate the clinical significance of soluble CD8 antigen (sCD8), which is released from CD8+ suppressor/cytotoxic T-lymphocytes, we determined sCD8 levels in the sera of 82 consecutive patients with newly diagnosed untreated Hodgkin's lymphoma who were entered into prospective trials of the German Hodgkin's Disease Study Group. sCD8 levels were significantly higher (p less than 0.01) in stage IV (781 U/ml, n = 19) than in stages I-IIIB (443 U/ml; n = 63). Patients with B-symptoms (n = 36) had slightly higher levels (611 U/ml) than patients without (n = 46) systemic symptoms (447 U/ml; p = 0.08). In 77 patients evaluable for response, the complete remission (CR) rate of patients with sCD8 less than 750 U/ml was higher (54/60 or 90%) than that of patients with sCD8 greater than 750 U/ml 11/17 or 65%; p = 0.01). The time to treatment failure was significantly longer in patients with sCD8 less than 750 U/ml (p = 0.008), even among the group with stages IIIB/IV only (p = 0.04). Our data suggest that the pretreatment levels of sCD8 in adult patients with Hodgkin's lymphoma have prognostic relevance, and that they should be determined especially in patients with advanced disease. Increased understanding of the role of sCD8 may shed light on the pathogenesis of Hodgkin's disease.

Adolescent↗
PubMed1990

Detection of a soluble form of the CD30 antigen in sera of patients with lymphoma, adult T-cell leukemia and infectious mononucleosis.

Using a sandwich enzyme-linked immunosorbent assay (ELISA) we were able to detect a soluble form of the CD30 antigen (CD30s) in the supernatant of cell lines expressing membrane-bound CD30 and in T and B cells after transformation with human T-cell leukemia virus (HTLV-I) and Epstein-Barr-Virus (EBV). While CD30s was not found in 250 healthy controls, it was detected in the sera of patients with Hodgkin's disease (23/100), anaplastic large-cell (6/9), angioimmunoblastic (2/2) and one unclassified high-grade non-Hodgkin's lymphoma (NHL), as well as in 18/20 patients with acute adult T-cell leukemia (ATL, HTLV-I-positive). It was absent in a large number of patients with other high-grade NHL, all low-grade NHLs, acute or chronic leukemias and solid tumors. The only non-malignant disease with detectable levels of CD30s was infectious mononucleosis (9/10). The membrane-bound form of CD30 has a molecular weight of 120 kDa. Western blot analysis revealed that CD30s in the serum of patients has a molecular weight of 88 kDa, identical to the antigen released by cell lines in vitro. CD30s disappeared in all originally positive cases after successful treatment and reappeared in relapsing patients. Thus, CD30s may be useful as a specific marker for disease activity of certain types of lymphoma and ATL.

Adult↗
PubMed1987

A new V gene expressed in lambda-2 light chains of the mouse.

We have partially sequenced the light chain variable regions expressed in three IgM-producing hybridomas generated from newborn mice or from manipulated animals suppressed for IgM production. In these lines a new V gene (V-lambda-X), exhibiting less than 60% homology to any known lambda or kappa V gene, is rearranged to J-lambda-2. The light chains produced by these cells contain the lambda-2 constant domain, but are not recognized by goat antisera raised against conventional mouse lambda light chains.

Animals↗
PubMed1987

In vivo generation and function of B cells in the presence of a monoclonal anti-IgM antibody: implications for B cell tolerance.

C57BL/6 mice were chronically treated with milligram doses of the noncytotoxic monoclonal anti-mu b antibody MB86 (IgG1, kappa) from birth or from fetal life. The spleens of the manipulated animals contained large numbers (25% as compared to control mice) of B lineage cells which expressed IgMb on the surface after overnight incubation in vitro. The spleens also contained B cells whose surface IgM was unreactive with antibody MB86. A few such cells were immortalized by cell fusion. They included cells secreting mu together with lambda 2 chains which apparently prevent recognition by antibody MB86, and a point mutant in the first constant domain of the mu chain, changing the b to the a allotype. Cells expressing MB86- surface IgM did not selectively expand under MB86 treatment over the first few months of life. Serum Ig levels in the manipulated mice were normal except for IgM which was undetectable in most instances. In some animals low levels of MB86- IgM molecules were produced. At 7 weeks of age, mice treated with MB86 from birth produced normal-size IgG anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) responses with the usual predominance of lambda 1 chain-bearing IgG1 antibodies. At the age of 5-6 months, and also in young mice treated with MB86 from fetal life, the responses were variable and presumably oligoclonal, with a tendency towards the production of antibodies with gamma 3 heavy and lambda 2 or lambda 3 light chains. We interpret these results to mean that B cells hit by antibody MB86 from the time of their generation become unresponsive to T cell-dependent stimulation, but are still able to expand. Occasionally, they escape functional suppression through class switching (to IgG3) upon mitogenic stimulation. At birth, C57BL/6 mice contain a mature B cell population which mediates normal immune responses under MB86 treatment and eventually dies out. Taken as a model of tolerance induction in B cells, the data provide evidence for "tolerant" cells and support the concept of an early phase of sensitivity to tolerance induction in B cell differentiation. The anti-NP response under MB86 treatment differed profoundly from control responses in idiotypic terms, but became normal as the animals recovered from suppression. This may reflect blockade by MB86 of idiotypic selection within the B cell population.

Animals↗
PubMed1981

T-lymphocyte subpopulations in the peripheral blood of patients with Crohn's disease.

Samples of peripheral blood from 26 patients with Crohn's disease (CD) and 26 healthy age- and sex-matched controls were tested simultaneously for B and T lymphocytes and T-lymphocyte subpopulations with receptors for IgM (TM) and IgG (TG). Patients with CD had reduced proportions of T lymphocytes, and this reduction showed a significant correlation to the CD activity index (r = -0.65, p less than 0.01). There was slight reduction of TM only (p less than 0.05) inpatients with highly active disease but not in the total population of patients studied. Proportions of B and TG cells were similar in patients and controls. Patients with no clinical or radiological but histological signs of active disease had T lymphocytes and subpopulations like patients with inactive disease. This suggests that the reduction of T cells and T-cell subpopulations in CD are secondary effects. With regard to T-lymphocyte subpopulations, our results are in contrast to a recently published report and do not suggest that analysis of T cells according to the expression of Fc receptors helps in the understanding of functional changes in the T-cell system in patients with CD.

Adolescent↗
PubMedDate not supplied

Increased levels of circulating interleukin-6 in patients with Hodgkin's disease.

Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow-up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6.

Adolescent↗
PubMedDate not supplied

Birmingham vasculitis activity score, disease extent index and complement factor C3c reflect disease activity best in hepatitis C virus-associated cryoglobulinemic vasculitis.

OBJECTIVE: Clinical measures of vasculitis activity (Birmingham vasculitis activity score = BVAS) and disease extent (Disease Extent Index = DEI), serological and immunological parameters were evaluated for the monitoring of hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV), treated with either cyclophosphamide or interferon-alpha 2b depending on disease severity. METHODS: Serial serum samples of 15 patients with HCV-associated CV were analyzed, and BVAS, DEI, serological and immunological parameters were recorded at diagnosis and during therapy. Eight patients were treated with interferon-alpha 2b and 7 patients with cyclophosphamide. RESULTS: A complete or partial response of the CV was seen in both treatment groups. BVAS, complement factor C3c, cryoglobulinemia, and rheumatoid factor significantly decreased in both treatment groups during 6 months (p < 0.05). DEI decrease was significant in the cyclophosphamide group (p < 0.05), and there was a trend in the interferon-alpha 2b group (p = 0.06). BVAS and DEI were significantly positively correlated, and both parameters were significantly negatively correlated with C3c levels in both treatment groups (interferon-alpha 2b/cyclophosphamide: r = -0.89, p = 0.001 versus r = -0.87, p < 0.001, respectively) whereas other parameters were not, e.g. ESR and CRP. CONCLUSIONS: Patients with different degrees of disease severity, treated with either cyclophosphamide or interferon-alpha 2b depending on their disease activity, achieved remission of their CV. BVAS, DEI and C3c were especially useful in the follow-up of HCV-associated CV. C3c correlated with BVAS and DEI during therapy and provided additional information about vasculitis activity that was not reflected by other serological or immunological parameters, e.g. ESR or CRP.

Adult↗