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S Hoch

Publications and source records attributed to S Hoch.

At least 19 recordsLinked to original sources

VH and VL gene elements that encode human antibodies to DNA.

We have determined the cDNA sequence of variable regions of heavy and light chains of three antibodies with low affinity to DNA. The variable heavy chains were found to result from utilization of VH gene elements that have been identified previously in other low-affinity anti-DNAs. These VH gene elements, VH26 and VH1.9III, are expressed in association with different D gene-encoded CDR3s than in the other antibodies. The variable light chains were found to be encoded by VL gene elements that have not previously been identified in anti-DNAs. The recurrent identification of only 10 germ line VH genes in 22 low-affinity anti-DNAs indicates that there is a high probability that all of the VH gene elements that confer reactivity with DNA have been identified. Previous studies have suggested that high-affinity antibodies to DNA result from an antigen-driven process of affinity maturation. However, only 6 of 13 high-affinity antibodies to DNA are derived from this set of low-affinity VHs, indicating that DNA is unlikely to be the driving antigen.

Antibodies, Antinuclear

Characterization of the polymerase activity associated with cultured peripheral blood mononuclear cells from patients with Kawasaki disease.

The particulate fractions of culture supernatants from peripheral blood mononuclear cells from 39 patients with Kawasaki disease (KD) were examined for the presence of particle-associated reverse transcriptase activity. The peak polymerase activity was significantly higher in cultures from KD patients compared to controls (mean = 6.4 versus 3.6 pmol of dTMP incorporated, p = 0.001). PBMC cultured between the 3rd and 9th wk after onset of fever were most likely to be associated with reverse transcriptase activity. Peak polymerase activity was positively associated with older age (r = 0.41, p = 0.01) and greater magnitude of the serum IgA response at 7-14 d after onset of fever (r = 0.45, p = 0.01) and IgM response at 6-9 wk after onset of fever (r = 0.46, p = 0.01). The appearance of enzyme activity was not associated with a decrease in viability of the cultured cells. A purified enzyme preparation showed radiolabel incorporation only with an RNA template with DNA primer. These data suggest that circulating mononuclear cells from KD patients may harbor a polymerase-associated agent and that these cells can be most readily detected in the early convalescent phase of KD from older patients who mount a marked humoral immune response.

Age Factors

The timing of menarche in juvenile rheumatoid arthritis.

A study of the age of menarche in juvenile rheumatoid arthritis (JRA) patients was undertaken to determine what factors affect the timing of menarche. There was a significant difference between the mean age of menarche for the 68 JRA patients and 46 controls (p = 0.015). No clear etiology for this difference was elucidated. Polyarticular-onset JRA patients had the oldest age of menarche, but this finding was of marginal statistical significance (p less than 0.05,pcorr less than 0.25). The multivariate model that included onset type, steroid use, and duration of disease weakly predicted age of menarche in the JRA group. This model suggests that, exclusive of height and weight parameters, duration of disease was the most important predictor of menarche in JRA.

Adrenal Cortex Hormones

Identification and sequence of the VH gene elements encoding a human anti-DNA antibody.

Antibodies to DNA similar to those found in patients with systemic lupus erythematosus (SLE) and autoimmune mice can be derived from the lymphocytes of normal individuals. It is not known whether these normal derived anti-DNA antibodies are made from the same VH gene elements as the anti-DNA antibodies made by SLE patients. To begin to answer this question, we examined mu chain cDNA clones from human hybrid clone C6B2 producing anti-DNA antibodies. The sequence of the 500 base pair restriction fragment containing the variable region (5' terminus) was determined and was sequenced. This antibody uses a VHII heavy chain subgroup gene, a J3 joining segment, a hitherto unknown D segment, and a previously reported leader sequence. Significant homology was found to a mouse anti-DNA antibody sequence in the use of VH subgroup in J3, and in the hypervariable regions with a shared Ser-Tyr construction in CDR1 and an identical five amino acid residue stretch in CDR2. Comparison with the limited sequence data of published SLE monoclonal anti-DNA antibodies, both human and mouse, suggests that this shared Ser-Tyr may be important in some but not all antibodies to DNA. Comparison of C6B2 antibody is made with other known antibody sequences with identification of those residues likely to be part of the antigen binding site.

Amino Acid Sequence

Specificity analysis of human anti-DNA antibodies.

Human hybrids producing anti-DNA antibodies were generated by the fusion of pokeweed mitogen-stimulated splenic lymphocytes from a child with sickle cell anemia to GM4672. Of 19 hybrids, three (15%) produced anti-DNA antibody as detected by an enzyme linked immunosorbent assay. One subclone from each of these three hybrids was then characterized. All produced IgM antibody in large amounts ranging from 22 to 266 micrograms/ml per million cells per 24 hr. All three antibodies bound both double- and single-stranded DNA. Competitive inhibition assays revealed the greatest inhibition of DNA binding with the ribohomopolymers polyinosinic and polyguanylic acid. A complex pattern of cross-reactivity with various other polynucleotides and with some phospholipids was observed. Subtle differences were found among the three antibodies in light chain class and some of the binding specificities. By using a modified Farr assay, all three monoclonals were found to be of low to intermediate affinity. These results confirm that anti-DNA antibodies apparently equivalent to those seen in patients with SLE can be derived from "normal" nonautoimmune individuals.

Animals

Monocyte bone degradation: in vitro analysis of monocyte activity in patients with juvenile rheumatoid arthritis.

We examined the ability of the mononuclear phagocyte in vitro to degrade 45Ca-labeled bone particles to determine whether this assay allowed us to monitor disease activity in patients with juvenile rheumatoid arthritis. The monocytes from patients with juvenile rheumatoid arthritis receiving no anti-erosive therapy (n = 10) degraded significantly more bone than did cells obtained from normal controls (n = 10, P less than 0.001) or patients with juvenile rheumatoid arthritis receiving either gold thioglucose (n = 4, P less than 0.001) or D-penicillamine (n = 6, P less than 0.005). In two patients monitored for either 8 or 11 months, results of monocyte assays were found to parallel the clinical course. We conclude that in vitro monocyte bone degradation assays may provide a means of assessing joint activity in patients with juvenile rheumatoid arthritis. Further, this study and others indicate that mononuclear phagocytes are capable of causing erosive changes.

Adolescent

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis.

The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (chi 2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.

Adolescent

Frequency of anti-DNA antibody producing cells from normals and patients with systemic lupus erythematosus.

The frequency of anti-DNA antibody producing cells from normals and patients with systemic lupus erythematosus (SLE) was determined. Peripheral blood lymphocytes (PBL) from normals and patients with SLE were cultured for 8 and 15 days with and without transformation by Epstein-Barr virus (EBV). Culture supernatants were examined for the presence of anti-DNA antibody using an enzyme-linked immunosorbent assay. We found that PBL from patients with SLE spontaneously produce anti-DNA antibodies whereas PBL from normals do not. After EBV transformation, anti-DNA antibody producing cells were detected in both cultures from patients with SLE as well as from normals. These data suggest that the high levels of anti-DNA antibody observed in patients with SLE represent activation of B cells committed to anti-DNA antibody production and that such cells are present but are not activated in normal individuals.

Adult

Complement activation by antibodies to Sm in systemic lupus erythematosus.

An enzyme linked immunosorbent assay was developed to quantitate antibodies to Sm (anti-Sm) and to measure complement activation by anti-Sm in vitro. Anti-Sm in plasma of patients with systemic lupus erythematosus (SLE) were bound to purified Sm bound to polyvinyl chloride microtitre plates and assayed for bound IgG or IgM using enzyme linked anti-gamma or anti-mu. The activation of C4 by anti-Sm was measured by adding diluted normal human serum (complement) to the wells and quantitating the amount of C4 bound to the well surface using (Fab')2 goat anti-C4 followed by enzyme linked rabbit anti-goat IgG. The plasmas of 12 of 36 patients with SLE contained anti-Sm and all 12 activated complement (complement activating anti-Sm). Twenty-eight plasmas containing anti-Sm from 12 patients with SLE were studied. Ten of the 12 patients had anti-Sm of the IgG class whereas two had anti-Sm of both IgG and IgM classes. The amount of C4 activating anti-Sm correlated significantly with the in vivo activation of C4 measured by rocket immunoelectrophoresis for C4d and C4, suggesting that complement activation by anti-Sm is important in vivo.

Antibodies, Antinuclear

Monocyte receptor function in patients with rheumatoid arthritis.

Monocytes from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and normal volunteers were studied for abnormalities of Fc and C3 receptor function. Monocytes from the majority of 22 patients with active RA showed enhanced E-rosette formation and Ea phagocytosis compared to monocytes from 20 normal volunteers and 10 OA patients, However, no significant differences in binding of EAC or uptake of iodinated aggregated gamma globulin were found among the 3 groups. Corticosteroid-treated RA patients exhibited significant depression of EA-rosette formation and phagocytosis. These results suggest that there is modulation of EA receptor function in monocytes from RA patients.

Adult

[Letter from Africa].

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Education, Nursing, Diploma Programs

Flushable stent-system for internal drainage in occlusive jaundice.

The effectiveness of biliary stents may be reduced as a result of obstruction by tumor material, bile salts or detritus. To circumvent this problem we developed a prosthesis system, which allows flushing and repetitive radiological control via a subcutaneous port. Prostheses were implanted in 26 patients presenting with inoperable occlusive lesions of the bile duct. Patency was regularly monitored by checking the bilirubin and alkaline phosphatase levels and using port-cholangiography. Catheter function was easily maintained in 92% of the patients and ended upon malignancy related death. In case of dysfunction, drainage could generally be restored with intensive flushing. This new flushable stent-system was easily implantable, could be exchanged without renewed percutaneous transhepatic puncture and allowed flushing, external drainage, bile probes for bacteriological examinations and follow up cholangiography via the subcutaneous placed port.

Cholestasis