Biomedical subjects
Publications and source records attributed to D A Gerber.
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A randomized cooperative double-blind trial of oral L-histidine for the treatment of rheumatoid arthritis was carried out. Patients were treated with either L-histidine 4.5 g daily, or placebo, for 30 weeks. None of the clinical measurements showed an advantage of histidine over placebo. A small decrease in rheumatoid factor titer and a small increase in hematocrit were found only in the histidine group. There was suggestive evidence of a beneficial effect of histidine in patients with more active and prolonged disease, based upon subjective doubld-blind evaluations by physicians and patients. No adverse effects of histidine therapy were noted. Histidine cannot be advocated as a therapeutic agent in rheumatoid arthritis, but further studies in certain groups of patients seem justified.
The longterm administration of prednisone and gold to patients with rheumatoid arthritis (RA), in doses that decreased the sedimentation rate (p less than 0.05), did not alter the serum histidine concentration (p greater than 0.5). In patients with RA receiving various combinations of aspirin, prednisone, and gold, the regression lines relating the serum histidine concentrations to the sedimentation rates had similar slopes but different elevations compared to patients receiving no anti-inflammatory drugs. In the patients receiving anti-inflammatory drugs, the regression lines were displaced so that in patients with similar serum histidine concentrations, the stronger the antirheumatic therapy, the less abnormal the sedimentation rate. These observations are consistent with the hypothesis that hypohistidinemia contributes to the pathogenesis of RA.
A dose of 3.7 g of free-L-histidine was administered by mouth to 26 patients with active rheumatoid arthritis and to 29 control subjects. The patients with rheumatoid arthritis had a statistically significant (p=10(-12)) lower pretreatment concentration of free histidine in serum (1.20 mg/100 ml, SE=0.04) than the control subjects (1.90 mg/100 ml, SE=0.06). However, there were no statistically significant differences between rheumatoid and control subjects with respect to the serum histidine concentrations 1 hr, 3 hr, and 4 hr after the ingestion of L-histidine. The changes in the serum histidine concentrations at 1 hr, 3 hr, and 4 hr (compared to the pretest values) were also not significantly different in the patients with rheumatoid arthritis relative to the control subjects. This study suggests that the subnormal free serum histidine concentration of rheumatoid arthritis is not associated with abnormal serum levels of free histidine following an oral load of free histidine.
A study of sera from 285 patients with definite or classical rheumatoid arthritis (including 37 patients receiving no anti-inflammatory drugs) and sera from 67 healthy subjects has confirmed 10 published reports of a statistically significant decreased blood histidine concentration in patients with rheumatoid arthritis. Contrastingly, in sera from 231 patients with a variety of acute and chronic illnesses other than rheumatoid arthritis, no statistically significant hypohistidinemia was observed either in the group as a whole or in association with the administration of aspirin, prednisone, indomethacin, phenylbutazone, or dextropropoxyphene. In the patients with rheumatoid arthritis there was a statistically significant correlation between the serum histidine concentration and the following: Westergren sedimentation rate (r=-0.33, P smaller than 10- minus 9), grip strength (r=0.26, P smaller than 10- minus 9), hematocrit (r=0.23, P smaller than 10- minus 9), duration of morning stiffness (r=-0.14, P=10- minus 5), walking time (r=-0.13, P=10- minus 4), latex titer of rheumatoid factor (r=-0.11, P=0.001), and the duration of arthritis (r=-0.06, P=0.05). There was no statistically significant association between the serum histidine concentration and the duration of rheumatoid arthritis in the 151 patients with disease of 0-10-yr duration (r=0.02, P=0.5), the sex of the patient, or the presence of antinuclear antibody (R=0.007, P=0.9). The serum histidine concentration was less in rheumatoid patients receiving steroids (P=0.00001), gold (P=0.009), and aspirin (P=0.15) than in rheumatoid patients not receiving these drugs. This study indicates that histidine determinations on properly preserved casual serum samples can be helpful in the diagnosis of rheumatoid arthritis and in the evaluation of the activity of the disease.
The serum concentrations of 12 free amino acids (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine, phenylalanine, serine, threonine, tyrosine, and valine) were measured in 26 patients with rheumatoid arthritis and in 12 control subjects. Patients with rheumatoid arthritis had a low serum histidine concentration (P equals 0.002) but no abnormality of any other amino acid concentration or of the combined concentration of the measured amino acids, excluding histidine. These data and 22 other reported studies provide strong evidence for the presence of hypohistidemia, not associated with generalized hypoaminoacidemia, in patients with rheumatoid arthritis. (J Rheumatol 2: 384-392, 1975).
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Hyaluronic acid (4 mg/ml) augmented elevenfold the copper-catalyzed (7 muM) thermal (63 degrees C, 2 hours) aggregation of human gamma globulin (2 mg/ml) in 0.075 M phosphate buffer, pH 7.4. Almost no augmentation of aggregation occurred with hyaluronidase-treated hyaluronate. Hyaluronate-augmented copper-catalyzed thermal aggregation was inhibited by L-histidine, gold thiomalate, N-ethylmaleimide, p-chloromercuribenzoic acid, and ethylenediaminetetraacetic acid. Together with previous reports of a decreased blood histidine concentration in rheumatoid arthritis, these studies provide a possible explanation for the affinity of this disease for joints.
A mixture of histidine, cystine, and copper mimicked gold thiomalate, N-ethylmaleimide, and p-chloro-mercuribenzoic acid in inhibiting sulfhydryl-disulfide interchange-mediated denaturation of human gamma globulin, bovine serum albumin, and diluted human serum. Measurable inhibitory effects were obtained with a mixture of physiologic concentrations of L-histidine, L-cystine, and copper. This work suggests a mechanism by which the hypohistidinemia of rheumatoid arthritis could contribute to the pathogenesis of the disease.