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Biomedical subjects

I Kushner

Publications and source records attributed to I Kushner.

At least 109 records · Page 6Linked to original sources
PubMed1979

Immunochemical characteristics of antibodies to DNA in patients with active systemic lupus erythematosus.

To investigate the suggestion that qualitative immunochemical characteristics of antibodies to DNA (anti-DNA) may be of importance in the pathogenesis of nephritis in systemic lupus erythematosus (SLE), we used the Crithidia luciliae (CL) immunofluorescence test to determine the titre, immunoglobulin (Ig) class and complement-fixing activity of anti-DNA in thirty-five patients with active SLE. Eighteen of these patients had active lupus nephritis (Group I) and the remaining seventeen had no clinical evidence of renal involvement (Group II). Anti-DNA was detected in twenty-eight patients, and was present more frequently and in higher titre (P less than 0.01) in Group I than in Group II. Anti-DNA of all three Ig classes studied (IgG, IgM and IgA) was present in twenty-three out of twenty-eight cases. The ratio of IgG to IgM anti-DNA did not differ in the two groups of patients. Complement-fixing antibodies were detected in thirteen patients in Group I and five patients in Group II. The titre of complement-fixing activity was strongly correlated with titre of anti-DNA. DNA-binding capacity was also determined in these by a millipore filter (MF) assay. A highly significant correlation between DNA binding by MF and CL was found in Group I patients, while no correlation was found in Group II patients. These findings suggest that (1) anti-DNA with specificity for determinants found in CL, presumably native DNA, are more highly correlated with the presence of active renal lupus than are antibodies directed toward other DNA determinants, and (2) the major characteristic of anti-DNA found to be associated with nephritis was quantity of antibody. Most patients had anti-DNA of all Ig classes regardless of the presence of renal disease. Complement-fixing activity of anti-DNA could not be related to the occurrence of renal disease independently of anti-DNA titre.

Antibodies, Antinuclear↗
PubMed1978

Control of the acute phase response. Demonstration of C-reactive protein synthesis and secretion by hepatocytes during acute inflammation in the rabbit.

To determine the cell of origin of C-reactive protein (CRP) and to cast light on the mechanisms leading to the acute phase response, we used an immunoenzymatic technique to visualize this protein in livers from rabbits at intervals after intramuscular injection of turpentine. CRP was detected only in hepatocytes. 8 h after turpentine injection, CRP was demonstrated in occasional periportal hepatocytes. With time, larger numbers of positive cells were detected successively in perilobular, midlobular, and centrilobular areas. On electron microscopy, CRP was detected in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER), and Golgi apparatus (GA). When colchicine was administered to inhibit cellular secretion of CRP, intensity of reaction and number of CRP-containing hepatocytes were substantially greater than without colchicine, but the sequence of intralobular distribution was similar. At peak serum response 38 h after turpentine injection, CRP could be demonstrated in most hepatocytes. Electron microscopic studies showed accumulation of CRP on membranes and lumina of RER, SER, GA, and in cytoplasmic vacuoles. These findings indicate that CRP is produced by progressively increasing numbers of hepatocytes after inflammatory stimulus and suggest that a mediator, acting initially in portal zones, is responsible for recruitment of cells to CRP production.

Animals↗
PubMed1978

A subgroup of ankylosing spondylitis associated with HLA-B7 in American blacks.

In a study of 34 American black patients with primary ankylosing spondylitis, 18 were found to be HLA-B27-negative. Of these, 10 possessed HLA-B7 (55.6%) compared to 23.7% of 59 B27-negative black controls (P less than 0.025, relative risk = 4). On comparing these 10 B7-positive patients (group I) with 16 B27-positive black patients (group II), a difference in mean age at onset of disease was found: 33.6 years in group I and 22.2 years in group II (P less than 0.005). In addition, a family history of ankylosing spondylitis was absent in group I patients but present in 6 patients in group II (P = 0.034). These findings indicate an association between HLA-B7 and ankylosing spondylitis in American blacks and suggest that these patients who lack B27 but possess B7 represent a subgroup of patients with this disease.

Adult↗
PubMed1978

HLA--B27 homozygosity in ankylosing spondylitis: relationship to risk and severity.

The observed frequency of apparent homozygotes for HLA--B27 (15.5%) was significantly greater than the estimated expected frequency (4.2%) among 58 B27-positive Caucasian patients with ankylosing spondylitis (AS) (P less than 0.0005). Search of the literature uncovered four other studies in each of which the frequency of apparent homozygotes was shown by our analysis to be greater than expected. These analyses indicated that B27 homozygotes are more susceptible to developing AS than are B27 heterozygotes. Comparison of the clinical features of AS showed no differences between heterozygotes and apparent homozygotes except for a higher frequency of involvement of peripheral joints in the latter group.

Gene Frequency↗
PubMed1978

Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction.

In order to investigate the magnitude and kinetics of the C-reactive protein (CRP) response after differing degrees of tissue injury, we studied changes in serum concentration of this acute phase protein in 19 patients after mild or extensive acute myocardial infarction. An increase in serum CRP concentration was seen in all patients. The rate of increase in concentration was found to be exponential, with a mean hourly rate constant for the entire group of patients of 0.085 (doubling time, 8.2 h). Patients with extensive infarction attained mean serum CRP levels about 4 times as great as did patients with mild infarction. No difference could be shown in the mean rate constant between these groups, the greater CRP response in the former group resulting principally from a more protracted period of rise in serum CRP concentration. A lag period before serum CRP levels began to rise was noted in only 4 of the 13 patients in whom this could be assessed. 7 of 10 patients with presumed unstable angina (coronary insufficiency) showed no rise in CRP concentration, while a small increase as noted in 3 patients. The data suggest that acute tissue injury, such as myocardial infarction, rapidly leads to acceleration in synthesis of CRP, and that the duration of this period of acceleration is related to the extent of tissue injury.

Acute Disease↗
PubMed1977

Improvement of rheumatoid arthritis following splenectomy for Felty syndrome.

A patient with Felty syndrome underwent splenectomy because of persistent high fever, leg ulcer, and granulocytopenia. Subsequently, his rheumatoid synovitis went into prolonged remission. In addition, the leg ulcer healed; his WBC count, hemoglobin level, temperature, ESR, and weight returned to normal; the rheumatoid factor titer dropped substantially; and the antinuclear antibodies disappeared. These changes have persisted to the present time, more than 5 1/2 years after surgery.

Adult↗
PubMed1977

Secondary gout in hemoglobinopathies: report of two cases and review of the literature.

Although patients with hemolytic hemoglobinopathies characteristically are over-producers of urate, and hyperuricemia is frequently recognized, clinical gout has rarely been reported in such patients. Our evaluation of 2 premenopausal women with gout led to the diagnosis of previously unrecognized hemoglobinopathies (SC disease and CC disease). Investigation of these 2 patients and review of the reported cases of gout in patients with hemoglobin S or C disorders suggest that relatively minor abnormalities of renal function in these patients may lead to early development of significant hyperuricemia. With increasing lifespan of patients with hemolytic hemoglobinopathies and the likelihood of increased occurrence of renal function abnormalities, it is anticipated that gout will more frequently be responsible for joint symptoms in such patients.

Adolescent↗
PubMed1977

An immunofluorescent method using Crithidia luciliae to detect antibodies to double-stranded DNA.

The immunochemical specificity of the immunofluorescent Crithidia luciliae method for detection of antibodies to double-stranded DNA (dsDNA) was confirmed by demonstrating abolition of staining by DNase digestion and by absorption with dsDNA. This method was less sensitive than a Millipore filter method for detecting antibodies to DNA. It was positive only in subjects with systemic lupus erythematosus or drug-induced antinuclear factors. This technique appears suitable for study of the immunochemical characteristics fo antibodies to dsDNA.

Antibodies, Antinuclear↗
PubMed1977

Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis.

The clinical features of ankylosing spondylitis (AS) were compared in 63 HLA-B 27 positive (+) and 15 B27 negative (-) individuals with this disease. There were no differences in age at onset, functional class, degree of deformity, pain, severity of X-ray changes, or frequency of peripheral joint involvement or of reconstructive orthopedic surgery. These data demonstrated that skeletal manifestations of AS were essentially the same in B27(+) and (-) patients, and provide no evidence for the speculation that AS in B27(-) patients is milder or is a different disease from that occurring in B27(+) patients. On the other hand, acute anterior uveitis was found to be significantly more common in B27(+) patients, a fact suggesting that the "uveitis of AS" may in fact be an independent condition occurring in B27(+) individuals, rather than a manifestation of AS per se.

Black People↗
PubMed1977

HLA B27 in ankylosing spondylitis: differences in frequency and relative risk in American Blacks and Caucasians.

Twenty-eight HLA alleles of the A and B loci were determined in 23 American Blacks and 50 Caucasians with primary ankylosing spondylitis (AS). The prevalence of HLA B27 was significantly increased in American Black patients (48 per cent) vs Black controls (two per cent), but was much less than the 94 per cent found in Caucasian patients (controls eight per cent). The lower prevalence of B27 in American Black patients vs Caucasian patients was significant (p less than 0.001), and indicated that susceptibility to AS is not as closely associated with B27 in Blacks as in Caucasians. No other HLA antigen was significantly associated with AS in either racial group. Among B27 positive individuals, the relative risk of developing AS was significantly lower in American Blacks than in Caucasians. These data indicate that for diagnostic purposes, the absence of B27 is less important in ruling out AS in Blacks than in Caucasians.

Aged↗
PubMed1976

Molecular size of rabbit C-reactive protein synthesized in vitro.

This study was performed to determine whether immunologically detectable C-reactive protein synthesized by rabbit liver mince in vitro is a micro- or macromolecular precursor of CRP, or if it is native CRP. Employing gel filtration and density gradient techniques, the molecular size of CRP newly synthesized by minced rabbit liver from inflamed rabbits was found identical with that of native CRP. Since no evidence for hepatic synthesis of a precursor can be shown, increased CRP formation after inflammation must result from increased de novo synthesis.

Animals↗