bluuebunny/crossref_metadata_2025 huggingface dataset:
The costs of rheumatoid arthritis. a patient‐oriented study of chronic disease costs
Authors: Meenan Robert F. , Yelin Edward H. , Henke Curtis J. , Curtis David L. , Epstein Wallace V.
Published: February 2007

To detail the cost for one year of a chronic disease, 50 patients with Stage III rheumatoid arthritis were surveyed. Direct medical costs for this group were three times the national average, and 58% of these costs were covered by insurance. Indirect costs due to lost income were at least three times the direct medical costs, and transfer payments covered only 42% of these costs. Fifty‐eight percent of the study group also sustained a major psychosocial loss. Uncovered income losses were the greatest economic burden for individuals with chronic rheumatoid arthritis. This striking ratio of indirect to direct medical costs has important implications for medical practice and health policy.
Hla‐c locus antigens in hla‐b27 associated arthritis
Authors: Arnett Frank C. , Hochberg Marc C. , Bias Wilma B.
Published: February 2007

Frequecies of the HLA‐C locus antigens, Cw 1, Cw2, Cw3, and Cw4, were determined in 88 patients with spondylitic diseases and 88 matched and 64 B27‐positive normal controls. Both Cw1 and Cw2 were significantly increased in B27‐positive patients and B27‐positive controls as compared to B27‐negative patients and matched controls. Cw1 and Cw2 demonstrate strong linkage disequilibrium with B27. Their absence in B27‐negative patients suggests disease susceptibility is related to HLA‐B.
Complement‐fixing hidden rheumatoid factor in juvenile rheumatoid arthritis
Authors: Moore Terry L. , Zuckner Jack , Baldassare Andrew R. , Weiss Terry D. , Dorner Robert W.
Published: February 2007

Fifteen to twenty percent of patients with juvenile rheumatoid arthritis (JRA) have positive latex fixation tests (LFT), whereas approximately 46% have previously been demonstrated to have hidden rheumatoid factors (RF), i.e., 19S IgM RF which can be detected by the LFT after acid separation of the IgM‐containing fraction from serum. In this study, hidden RF were found in 59% of patients with seronegative JRA by use of a complement‐dependent hemolytic assay. The median titer of JRA patients was 1:42, and in healthy and disease controls it was 1:7. The difference was significant at P < 0.001. When data from patients with active disease were analyzed separately, the median titer for polyarticular JRA was 1:97 and for pauciarticular JRA, 1:91. The differences due to active disease were significant at P < 0.001 and P < 0.005, respectively.

The results demonstrate that the hemolytic assay is more sensitive than the LFT in determining the presence of hidden RF, and activity of disease correlates well with high hemolytic RF titers.
Histologic assessment of lymphokine‐mediated suppression of chondrocyte glycosaminoglycan synthesis
Authors: Taplits Michael S. , Crissman John D. , Herman Jerome H.
Published: February 2007

An experimental model has been developed to histologically assess the effect of T cell mitogen‐induced lymphokines derived from rabbit splenocytes on proteoglycan matrix depleted auricular cartilage explant glycosaminoglycan synthesis. Explant exposure to lymphokine was shown by light and electron microscopy to significantly suppress chondrocyte glycosaminoglycan regenerative capacity. This inhibitory effect was reversible in that synthetic activity could be restored by placement of explants in control media after as long as 12 days of lymphokine exposure.
Immunofluorescence studies of anti‐t cell antibodies and t cells in systemic lupus erythematosus
Authors: Steinberg Alfred D. , Klassen Lynell W. , Budman Daniel R. , Williams Gary W.
Published: February 2007

Peripheral blood T cells from patients with systemic lupus erythematosus (SLE) and age‐ and sexmatched controls were studied by flow microfluorometry by using SLE anti‐cell antibodies and fluorescein conjugated antibody to human IgM. Brightly staining cells were reduced in a number of patients with active SLE. Analysis of SLE T cells separated on a discontinuous stractin gradient indicated a preferential loss of cells, especially brightly staining cells, from one fraction. Quantitation of this phenomenon indicated that an average of >90% of the brightly staining T cells from that fraction was lost in active SLE. This preferential loss of a subpopulation of T cells in patients with active SLE may be responsible for many of their immunologic abnormalities.
Inhibition of collagen gelation by action of the superoxide radical
Authors: Greenwald Robert A. , Moy Wai W.
Published: February 2007

Superoxide anion, a highly reactive free radical, was generated in vitro using enriched purified xanthine oxidase. Collagen solutions exposed to superoxide radical failed to gel normally when heated to 37°C. The magnitude of the inhibition of gelation was proportional to duration of exposure and to flux of superoxide. Since inhibition of collagen gelation reflects alteration of collagen biochemistry, and/or collagen degradation, it is suggested that the action of free radicals produced in vivo by leukocytes may adversely affect the structural or functional integrity of cartilage and adjacent joint structures.
The kniest (swiss cheese cartilage) syndrome
Authors: Frayha Rida , Melhem Rafic , Idriss Hassan
Published: February 2007

A boy with the Kniest (Swiss cheese cartilage) syndrome is reported and the salient features of this rare chondrodystrophy are described. The unique polyarthropathy of this syndrome is characterized by symmetrical bony joint enlargements and fixed flexion contractures significantly contributing to the incapacitating nature of the disease.
Correlation of Serum and Cryoglobulin IgM with Activity, and Serum IgG with Remission
Authors: Steere Allen C. , Hardin John A. , Ruddy Shaun , Mummaw Jon G. , Malawista Stephen E.
Published: February 2007

Forty‐eight patients with erythema chronicum migrans (ECM) were studied prospectively for 6 to 18 months. Twenty‐six patients had no later symptoms, but 22 subsequently developed Lyme arthritis and 9 of them also experienced neurologic abnormalities. Eighty‐seven percent of patients with active ECM followed by subsequent involvement had cryoglobulins containing IgM compared to only 13% of those with active ECM and no later symptoms. The former group also had significantly lower IgG, C3, and C4 levels. Sixty‐seven percent of patients still had serum cryoglobulins when neurologic disease was most active, and 45% had them when joint symptoms were most severe, but only 11% continued to have small amounts in remission. The number of patients who continued to have serum cryoglobulins with recurrent attacks of arthritis decreased with time. In contrast, patients always had cryoglobulins in joint fluid, a finding Lyme arthritis shares with rheumatoid arthritis. The cryoprecipitates from 2 of 10 patients contained particles with internal structure, but their viral nature is problematic. All components of antisera obtained from goats and rabbits immunized with cryoglobulins were absorbed by normal human sera. The amount of IgM in cryoglobulins correlated directly with serum IgM, which generally rose during exacerbations and fell during remissions; serum IgG and IgA moved conversely. Thus, IgM was an important correlate of clinical disease activity and IgG of remission.
Increased Antibody‐Dependent Cell‐Mediated Cytotoxicity by Monocytes from Patients with Rheumatoid Arthritis
Authors: Waytz Paul H. , Douglas Steven D.
Published: February 2007

Antibody‐dependent cell‐mediated cytotoxicity (ADCC) was studied in adult patients with rheumatoid arthritis (RA) and in healthy controls. Three effector cell populations from the peripheral blood were studied which included a mixed mononuclear population, a monocyte‐depleted fraction, and a monocyte‐enriched fraction. The monocyte‐enriched fraction from patients with RA mediated a significantly increased degree of cytotoxicity. Enhanced cytotoxicity was more evident at low effector: target ratios. There was no significant difference in ADCC activity between patient cells and control cells when either the mixed mononuclear population or monocyte‐depleted population was studied as effectors. The enhanced effector function of the peripheral blood monocyte in this system may be further indication that mononuclear phagocytes are “activated” in patients with RA.
Drug acetylation phenotype unrelated to development of spontaneous systemic lupus erythematosus
Authors: Morris Richard J. , Freed Curt R. , Kohler Peter F.
Published: February 2007

To ascertain if a genetically determined slow drug acetylation rate is correlated with the development of spontaneous systemic lupus erythematosus (SLE), as it is in drug‐induced SLE, acetylation phenotypes of 27 patients with spontaneous SLE were determined after administration of dapsone. Thirty‐three percent were slow acetylators, 63% were rapid acetylators, and one was indeterminate, a distribution not significantly different from that expected in control subjects. Among 4 pairs of first‐degree relatives, all of whom had spontaneous SLE, 7 of the 8 individuals were rapid acetylators. We conclude that people who are slow acetylators are at no greater risk for developing spontaneous SLE than are rapid acetylators and that the slow acetylation phenotype is not correlated with familial SLE.
Quantitative sacroiliac joint scintigraphy
Authors: Ho George , Sadovnikoff Nicholas , Malhotra Chander M. , Claunch Ben C.
Published: February 2007

With quantitative sacroiliac joint scintigraphy (QSS), sacroiliac joint‐to‐sacrum (SIS) ratios ≥1.40 are abnormal for our method. High SIS ratios are associated with roentgenographically appreciated sacroiliitis and with early clinically evident sacroiliitis. Although highly sensitive, QSS abnormalities are not specific for inflammatory sacroiliac (SI) joint disease. High SIS ratios are also seen in rheumatoid arthritis, degenerative abnormalities of the lumbosacral spine, and metabolic bone disorder. Other disorders with roentgenographic SI joint abnormalities must be studied scintigraphically before QSS can be employed as a useful diagnostic test.
Hypocomplementemic urticarial vasculitis with glomerulonephritis and pseudotumor cerebri
Authors: Ludivico Charles L. , Myers Allen R. , Maurer Kenneth
Published: February 2007

Patients with recurrent urticarial vasculitis associated with arthralgias, abdominal pain, glomerulonephritis, and hypocomplementemia have been recently recognized (1–3). We are reporting a woman with similar multisystem involvement who has developed chronic pseudotumor cerebri. The only previously reported patient with this syndrome complicated by pseudotumor cerebri (4) exhibited the neurologic manifestation as an acute phenomenon only.
Arthritis after frostbite injury in children
Authors: Carrera Guillermo F. , Kozin Franklin , Mccarty Daniel J.
Published: February 2007

Two patients who suffered frostbite injury to their hands as children were recently observed. The characteristic clinical and radiographic features of arthritis secondary to frostbite are described. Joint changes may be the result of direct chondrocyte injury during cold exposure. Current theories of the pathogenesis and treatment of frostbite injury are reviewed briefly.
Articular cartilage preservation and storage
Authors: Brighton Carl T. , Shadle Chester A. , Jimenez Sergio A. , Irwni John T. , Lane Joseph M. , Lipton Mitchel
Published: February 2007

Articular cartilage slice explants were stored under various conditions, including freezing‐thawing at various rates by using dimethyl sulfoxide (DMSO) as a cryoprotective agent, incubating in standard tissue culture medium (MEM Eagle:NCTC 135:15% fetal calf serum) in 5% CO2 and air at 4°, 21°, and 37°C, and incubating in standard tissue culture medium containing 200 μg/ml α‐tocopherol (vitamin E) at 37°C after first ascertaining a dose‐response curve of vitamin E. Results indicated that articular cartilage slice explants did not survive freezing or storage at 4° and 21°C as measured by 35S uptake. When stored at 37°C in standard tissue culture in 5% CO2 and air, the slice explants remained viable for up to 60 days. The addition of α‐tocopherol to the medium resulted in significantly less release of previously incorporated 35S in stored cartilage slices and significantly less reduction of the amount of hexosamine present in the stored explants. α‐Tocopherol in the medium also preserved safranin O staining. Thus, the application of tissue culture techniques to the storage of articular cartilage made it possible to preserve cartilage slice explants in a viable, biochemically “normal” state.
Articular cartilage preservation and storage
Authors: Black Jonathan , Shadle Chester A. , Parsons John Russell , Brighton Carl T.
Published: February 2007

Mature rabbit articular cartilage in the form of distal femoral condyles, composite osteoarticular structures, were incubated in the presence of α‐tocopherol (200 μg/ml) over a period of time. Indentation testing and 35S uptake indicate preservation of sustained load carrying capacity and viability, respectively, in the presence of α‐tocopherol for up to 30 days in organ culture. Condylar cartilage stored in the absence of α‐tocopherol as well as frozen cartilage demonstrated progressive inability to resist sustained loading over time. Nonoptimal synthetic function apparently occurred in these latter two groups when compared to α‐tocopherol stored material.
Clearance of calcium pyrophosphate dihydrate crystals in vivo
Authors: Mccarty Daniel J. , Palmer David W. , James Christopher
Published: February 2007

The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injected into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 ± 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease.
The mechanism of phenotypic sex differentiation
Authors: Wilson Jean D. , Griffin James E. , George Fredrick W.
Published: February 2007

For the first 2 months of gestation, there is no difference in the development of male and female embryos. Gonadal differentiation then ensues, and the ovary and testis commence to synthesize their characteristic hormones at approximately the same time. The initial secretion of testosterone by the fetal testis and 17β‐estradiol by the fetal ovary appears to be independent of gonadotropin control. If an ovary or no gonad is present, the resulting phenotype is female; thus no gonadal hormones appear to be required for female development. In contrast, two secretions of the fetal testis are responsible for the imposition of the male phenotype. Mullerian regression factor, a poorly characterized peptide hormone, is responsible for suppression of the mullerian ducts, and testosterone accounts for the remainder of male development. The mechanisms by which testosterone causes this differentiative process have been deduced from studies in humans and animals of single gene mutations that interfere with androgen action. Testosterone itself is responsible for virilization of the wolffian ducts into the epididymis, vas deferens, and seminal vesicles, whereas the testosterone metabolite dihydrotestosterone induces the development of the male urethra and external genitalia. Both testosterone and dihydrotestosterone act by combining in the cell cytosol with a high affinity receptor protein that is translocated to the cell nucleus. In summary, chromosomal sex determines gonadal sex, and gonadal sex in turn dictates phenotypic sex.
Identification of a clinical subset of systemic lupus erythematosus by antibodies to the sm antigen
Authors: Winn Donna M , Wolfe J Frederick , Lindberg Donald A , Fristoe Frank H , Kingsland Larry , Sharp Gordon C
Published: February 2007

The clinical and renal histologic attributes of 135 systemic lupus erythematosus (SLE) patients with DNA and/or Sm antibodies were compared to determine if the presence of the Sm antibodies served as a marker for a specific subset of SLE. Although Raynaud's phenomenon was more frequent in patients with Sm antibodies (P < 0.005), serious central nervous system disease was over three times as common in patients with DNA antibodies (P < 0.005). Only one of 23 patients with Sm antibodies had diffuse proliferative glomerulonephritis on renal biopsy, whereas 6 of 14 patients with only DNA antibodies had this histologic finding (P = 0.01). The Sm antibody system may therefore identify a subset of SLE patients with milder central nervous system and renal disease.
Studies of serum immunoglobulin binding to synovial fibroblast cell cultures from patients with rheumatoid arthritis
Authors: Gruhn William B. , Mcduffie Frederic C.
Published: February 2007

Using a sensitive 125I‐protein A (PrA) binding assay to detect cell surface IgG, we have studied seven different synovial fibroblast cell cultures from patients with rheumatoid arthritis (RA). When these cultures were incubated in the presence of serum from 18 autologous and allogeneic RA patients (all seropositive), we were unable to detect significant IgG binding. Since IgM rheumatoid factor (RF) can block PrA binding, sera were absorbed with aggregated IgG to remove RF without affecting the results. Similar studies on three cell lines with seven rheumatoid sera were performed by antibody‐dependent cell‐mediated cytotoxicity. No significant cytotoxicity was observed. Since antibodies to collagen are present in rheumatoid sera, several cultures were incubated with ascorbic acid (12.5 μg/ml) to optimize synthesis of cell surface collagen. These culture conditions did not affect serum immunoglobulin binding by the 125I‐PrA assay. Thus, we can find no evidence for a direct humoral immune mediation of synovial proliferation in rheumatoid arthritis. These data do not support the hypothesis that the inflammatory process within the synovium of RA patients is an immunologic response to a fibroblast‐associated antigen in the synovial membrane.
Deficiency of T cell mediated regulation of anti‐dna production in systemic lupus erythematosus
Authors: Clough John D. , Frank Sheila A. , Calabrese Leonard H.
Published: February 2007

Isolated B cells from normal subjects and patients with systemic lupus erythematosus (SLE) could be stimulated to produce IgM anti‐DNA with pokeweed mitogen. Normal but not SLE allogeneic T cells abrogated this response. Normal but not SLE autologous T cells promoted a switch from IgM to IgG anti‐DNA production. SLE is characterized by at least two types of immunoregulatory abnormalities: a defect in T suppressor function and a defect in the IgM to IgG switchover.
5‐thiopyridoxine in rheumatoid arthritis: clinical and experimental studies
Authors: Huskisson E. C. , Jaffe I. A. , Scott Jane , Dieppe P. A.
Published: February 2007

Twelve patients with rheumatoid arthritis who had failed to respond to or developed side effects preventing further use of penicillamine were given 5‐thiopy‐ridoxine (5‐TP). These patients were compared with 48 patients with similar indications randomly assigned to placebo or penicillamine. Both 5‐TP and penicillamine were superior to placebo, and the effectiveness of the two active drugs was similar. Both produced a gradual amelioration of symptoms and signs of the disease accompanied by reduction in erythrocyte sedimentation rate, rheumatoid factor titer, and immunoglobulins. Nine patients on 5‐TP were able to continue treatment with good control of the disease for at least 18 months. Toxic effects included rashes, proteinuria, loss of taste, and mouth ulcers. Patients who had developed a particular side effect with penicillamine did not necessarily do the same with 5‐TP. This is the second mercaptan compound which has suppressive effects on the clinical and laboratory features of rheumatoid arthritis. Because of their similarities, 5‐TP and penicillamine were studied in various experimental systems in an attempt to find some common biochemical or pharmacologic action. Among the properties studied were the effects on copper, vitamin B6 metabolism, dermal collagen, and mixed disulfide formation. Results with animal models of inflammation were also examined. The only common action was enhancement of the secondary lesions of adjuvant arthritis.
In vitro penicillamine competition for protein‐bound gold(i)
Authors: Schaeffer N. , Shaw C. Frank , Thompson H. O. , Satre R. W.
Published: February 2007

The reactions of penicillamine with gold sodium thiomalate (Myochrysine), gold‐albumin complexes, and gold bound to urinary and kidney cytosolic proteins were examined. Large excesses of penicillamine (20 to 100: 1 penicillamine/gold ratios) are required to mobilize significant amounts of protein bound gold. Quantitative comparisons of cysteine and penicillamine displacements of serum albumin bound gold indicate that penicillamine is approximately 5–6 times more effective than cysteine. Uninary gold is observed to be present in low molecular weight and protein bound forms, which exist in a labile chemical equilibrium and can be shifted by addition of penicillamine. These results are discussed in terms of the structure of gold(I)‐penicillamine complexes and the distribution of gold(I) among protein and nonprotein thiol groups. The inappropriateness of using AuCl4− in vitro to study the biochemistry of chrysotherapy agents is delineated.
Hla antigens and rheumatoid arthritis association between hla‐drw4 positivity and igm rheumatoid factor production
Authors: Dobloug Jan H. , Førre Øystein , Kåss Erik , Thorsby Erik
Published: February 2007

Serologic HLA typing was carried out on 33 seropositive and 15 seronegative patients with rheumatoid arthritis (RA). Association with the DRw4 antigen was found only in seropositive RA (61%, compared with 27% in normal controls; P < 0.05, Fisher's exact test), whereas the antigen had a normal frequency in seronegative RA patients (27%). The serum concentrations of IgM and IgE immunoglobulins were significantly higher in seropositive than in seronegative RA patients (P < 0.01, Mann‐Whitney test), whereas the concentrations of the other immunoglobulin classes and of the complement factors C3 and C4 did not show any significant differences.
Familial chondrocalcinosis
Authors: Rodriguez‐Valverde V. , Tinture T. , Zuñiga M. , Peña J. , Gonzalez A.
Published: February 2007

The first‐degree consanguineous relatives of 46 patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease were examined for the presence of articular chondrocalcinosis. In 5 cases the process was familial, with 17 persons in the oldest living generation (mean age 69 ± 7.4) showing radiographic evidence of calcified cartilage. The clinical syndrome was characterized by a female predominance, late onset of symptoms with mild arthritic manifestations, and oligoarticular chondrocalcinosis. These data suggest that the familial type of CPPD crystal deposition disease is more frequent than formerly thought.
Comparison of high and low dose cyclophosphamide therapy in rheumatoid arthritis
Authors: James Williams H. , Reading James C. , Ward John R. , O'Brien William M.
Published: February 2007

Eighty‐eight patients with active rheumatoid arthritis from 8 Cooperating Clinics were evaluated in a 32‐week controlled, double‐blind trial comparing 150 mg daily to 75 mg cyclophosphamide daily. Improvement in the arthritis was seen in both grops, and there were no important differences between the two treatment groups in any of the 8 variables used to measure disease activity. Untoward effects were also similar for the two groups. These results differ from preliminary results reported earlier.
Acetylator phenotype in idiopathic systemic lupus erythematosus
Authors: Reidenberg Marcus M. , Levy Micha , Drayer Dennis E. , Zylber‐Katz Ester , Robbins William C.
Published: February 2007

The acetylator phenotypes of 21 patients from New York City and 29 patients from Israel with idiopthic systemic lupus erythematosus (SLE) were determined with dapsone or isoniazid. Thrity were slow acetylators, 17 were rapid, and 3 indeterminate. These cases plus published studies of acetylator phenotypes in indiopathic SLE show a worldwide distribution of 150 slow to 77 rapid instead of the expected 122:105 (P, < 0.001). The relationship between acetylator phenotype and possible etiologic agents is discussed.
Application of a radiometric ear assay for studies of adjuvant arthritis in rats
Authors: Gans K. R. , Heyner S. , Orzechowski R. F.
Published: February 2007

A radioisotopic method, originally developed for measuring the cellular response in delayed hypersensitivity lesions in mice, has been evaluated in adjuvant arthritic rats. Focal accumulation of 5‐iodo‐2'‐deoxyuridine‐125I (125IUdR) at a site of antigen challenge (left pinna) was measured and expressed as increased radioactivity in the challenged (left) over the unchallenged (right) ear (L/R ear ratio). Immunologic specificity of the assay was established with anti‐lymphocyte globulin (ALG)‐treated arthritic rats. ALG significantly inhibited the 125IUdR L/R ear ratio; normal rabbit globulin had no effect on this parameter. A significant negative correlation was observed between the 125IUdR ear ratios and subjective arthritic scores in established adjuvant disease. Certain characteristics of the 125IUdR radiometric ear assay in rats were established in several types of experiments: disappearance of the isotope from blood, whole body irradiation studies in turpentine‐injected rats, and cyclophosphamide pretreatment in a sheep erythrocyte antigenic system. The results of this study support the utility of the 125IUdR ear assay to quantify cellular accumulation at a site of antigen challenge in adjuvant arthritic rats and possibly other antigenic systems in this species.
Presentation of occult giant cell arteritis
Authors: Healey Louis A. , Wilske Kenneth R.
Published: February 2007

Temporal headache, blindness, and polymyalgia rheumatica are well‐recognized manifestions of giant cell arteritis. However, the disease may present in less evident fashion as shown by 30 of 74 patients with biopsy‐proven giant cell arteritis whose predominant complaint was not one of these cardinal symptoms. For this group of 30, the main problem was fever in 12 patients, anorexia, weight loss, and elevated serum alkaline phosphatase level suggesting an occult malignancy in 7, and unexplained anemia in 3. Four patients had a neurologic syndrome; 2 had diplopia and 2 acute weakness of one arm. Claudication was the chief complaint of 4 patients, involving the leg in 1, the arm in 1, and the jaw in 2. All patients responded well to steroid therapy.
Heterogeneity of the spontaneously expanded and mitogen‐induced generation of suppressor cell function of t cells on b cells in systemic lupus erythematosus
Authors: Ruiz‐Arguelles Alejandro , Alarcón‐Segovia Donato , Llorente Luis , Del Guidice‐Knipping JOSéa
Published: February 2007

Eighty percent of 31 untreated patients with systemic lupus erythematosus (SLE) and abnormalities in their spontaneously expanded and/or Con‐A‐induced suppressor cell function, but the association of defects detected with both systems was only 68%. Loss of spontaneous suppression related positively to disease activity (r = 0.641) and the number of Tγ cells (r = 0.624) whereas Con‐A‐induced suppression correlated negatively with disease activity (r = ‐0.456) and the number of Tγ cells (r = ‐0.089). Incubation of mononuclear cells from SLE patients in antiribonucleoprotein IgG caused further loss of suppression in some, but not all, instances. The suppressor cell dysfunction found in SLE may result from diverse mechanisms, including a basic defect in the generation of suppressor cells and the abrogation of suppressor function by autoantibodies.
Bone marrow as the major site of antierythrocyte autoantibody production in nzb mice
Authors: Cohen Philip L.
Published: February 2007

By use of a hemolytic plaque assay, it has been determined that most cells secreting the clinically important (anti‐X) erythrocyte autoantibody of NZB mice are located in the bone marrow. There was evidence of excessive polyclonal B cell activation in NZB spleen but not in bone marrow, despite the role of marrow as the major source of erythrocyte autoantibody. These findings suggest that polyclonal activation of B cells within the marrow does not lead to erythrocyte autoantibody production. Small but significant numbers of anti‐erythrocyte autoantibody producing cells were detected in the bone marrow but not in the spleens of normal mice, indicating that tolerance to erythrocytes may be less absolute in the bone marrow than in the spleen, or that the bone marrow serves as a repository for autoantibody secreting cells generated elsewhere.
The benign hypermobile joint syndrome
Authors: Jessee E. Forrest , Owen Duncan S. , Sagar Kiran B.
Published: February 2007

Benign hypermobility as defined by a modification of the Carter‐Wilkinson criteria was found in 31 of 637 healthy blood donors, a prevalence of 5%. No increased prevalence of arthritis/arthralgia or characteristics suggestive of Ehlers‐Danlos syndrome other than a possible familial predisposition were found when these 31 hypermobile subjects were compared to an age and sex matched two‐for‐one control group. Cardiac evaluation by auscultation, electrocardiogram, and echocardiogram showed no increased occurrence of mitral valve prolapse in hypermobile subjects. Thus the benign hypermobile joint syndrome appears to be one extreme of the range of normal joint motion and not a systemic connective tissue disorder.
Bone cell cultures as an experimental model
Authors: Wong Glenda L.
Published: February 2007

The isolation and separation of bone cells with populations enriched for osteoclastic or osteoblastic phenotypes are described. Such systems offer the opportunity to compare and contrast the controls exerted by hormones, ions, and other agents on the functions of the individual bone cell types and may in the future provide explanations for the changes seen in bone tissue in various diseased states.
Association of hla‐drw4 with rheumatoid arthritis in black and white patients
Authors: Karr Robert W. , Rodey Glenn E. , Lee Tsung , Schwartz Benjamin D.
Published: February 2007

The HLA‐A, B, C, and DR antigens were typed in 35 black and 35 white Americans with rheumatoid arthritis. The frequency of HLA‐DRw4 was increased in both the black and white patient groups compared to the race‐matched control groups. DRw4 was found in 45.7% of the black patients compared to 14.3% of the black controls (corrected P value <0.035) and DRw4 was found in 71.4% of the white patients compared to 40.0% of the white controls (corrected P value <0.035). These data indicate that immunogenetic factors related to DRw4 are important in the development of rheumatoid arthritis in American blacks as well as whites.
Impaired antigen‐specific suppressor cell activity in patients with rheumatoid arthritis
Authors: Keystone Edward C. , Gladman Dafna D. , Buchanan Russel , Cane Donna , Poplonski Lorraine
Published: February 2007

Antigen‐specific suppressor cell activity of peripheral blood mononuclear cells was investigated in 20 patients with rheumatoid arthritis (RA) and 16 age and sex‐matched healthy controls. Suppressor cell activity was generated by priming peripheral blood mononuclear cells with high dose antigen (ovalbumin) and adding the washed primed or control (unprimed) cells to autologous, optimally stimulated, target plaque forming cell (PFC) cultures. The ability of the primed cells to interfere with an optimal ovalbumin specific PFC response in the target culture was used as a measure of antigen‐specific suppressor cell activity. The results demonstrated that the mean (± SE) PFC response of the rheumatoid patients (669 ± 76 PFC/106 cells) was not statistically different from that of the normal controls (722 ± 83 PFC/106 cells), P = 0.1. However, reduced suppressor cell activity was observed in the rheumatoid patients relative to controls (46.4 ± 4.2% versus 64.6 ± 2.7% suppression, respectively; P < 0.001). No correlation was demonstrated between suppressor cell activity in rheumatoid patients and disease activity or therapy.
Permeability of hyaluronic acid solutions
Authors: Carr Marcus E. , Hadler Nortin M.
Published: February 2007

The permeability of hyaluronic acid solutions was measured in a chamber closed at each end by semipermeable membranes. Permeability was strongly concentration dependent below 1.0 gm% hyaluronic acid. Small changes in the ionic environment of 1.0 gm% hyaluronic acid solutions also altered permeability. The permeability of such solutions decreased by a factor of 4.7 in the presence of as little as 5 mM calcium ion and showed optimum permeability at pH 7.0. The pH optimum was not noted in hyaluronic acid preparations known to contain only small amounts of protein.
Treatment of behcet's syndrome with levamisole
Authors: De Merieux Paula , Spitler Lynn E , Paulus Harold E
Published: February 2007

The clinical response to levamisole in 11 patients with complete Behcet's syndrome was reviewed. Nine patients responded, 3 completely and 6 partially, with reduction in the number and severity of buccal and genital lesions. In 3 patients each, ocular inflammation and gastrointestinal involvement responded to levamisole, and in 1 patient neurologic status improved. Levamisole was purposely discontinued in 3 patients to assess its true role in disease control. Each patient experienced a flare. Reintroduction of therapy controlled the flare in all cases, although 1 patient subsequently relapsed while continuing therapy. Two patients failed to respond. Side effects necessitated permanent discontinuation of the drug in 2 respondent patients, but in no case did neutropenia or agranulocytosis develop. These preliminary results suggest that levamisole may be useful in the therapy of the various manifestations of Behcet's syndrome and that a controlled prospective study is indicated.
Polyclonally triggered B cells in the peripheral blood and bone marrow of normal individuals and in patients with systemic lupus erythematosus and primary sjögren's syndrome
Authors: Fauci Anthony S. , Moutsopoulos Haralampos M.
Published: February 2007

Numbers of B cells spontaneously secreting Ig (IgG, IgA, and IgM) were determined by a plaque‐forming cell (PFC) assay simultaneously in the peripheral blood and bone marrow of normal individuals, patients with systemic lupus erythematosus (SLE), and patients with primary Sjögren's syndrome. Normal individuals had 382 (± 89) PFC per 106 mononuclear cells in peripheral blood. Patients with either active or inactive Sjögren's syndrome had normal numbers of spontaneous Ig‐secreting cells in peripheral blood (P > 0.2). Conversely, patients with inactive as well as active SLE had markedly increased spontaneous PFC (P < 0.05 and P < 0.001, respectively). Patients with active SLE had significantly greater PFC than patients with inactive SLE: 3,984 (± 960) versus 1,605 (± 527) PFC per 106 mononuclear cells (P < 0.05). The lack of increased numbers of activated B cells in the blood of patients with Sjögren's syndrome was not explained by a preferential sequestration of activated B cells in the bone marrow. However, of particular interest was the finding that the bone marrow served not only as a major source of virgin B cells but as a lymphoid organ of either in situ activation of B cells or sequestration for activated B cells. Normal individuals had approximately a 20‐fold relative increase of activated B cells per 106 mononuclear cells in the bone marrow compared to peripheral blood, while patients with inactive and active SLE both had a 35‐fold relative increase in activated B cells in bone marrow compared to peripheral blood. The potential relevance of circulating activated B cells and their sequestration in lymphoid organs is discussed concerning the discrepancy in this regard between Sjögren's syndrome and SLE, and our understanding of the significance of polyclonal B cell activation in the pathogenesis of these diseases.
Effect of high‐dose methylprednisolone infusion on polymorphonuclear leukocyte function in patients with systemic lupus erythematosus
Authors: Daniel Perez H. , Kimberley Robert P. , Kaplan Howard B. , Edelson Henry , Inman Robert D. , Goldstein Ira M. , Mellon Andrew W.
Published: February 2007

We have studied the effect of high‐dose (1 gm) methylprednisolone infusion on polymorphonuclear leukocyte (PMN) function in 11 patients with active systemic lupus erythematosus (SLE). The only alteration of polymorphonuclear leukocyte function produced consistently by methylprednisolone was decreased adherence to plastic surfaces when tested 2 hours after infusion. This steroid‐induced abnormality, however, was transient. Cells obtained from patients 24 hours after a single dose of drug exhibited normal adhesiveness. These results indicate that single, large doses of methylprednisolone do not produce long‐lasting abnormalities of PMN function in patients with lupus.
Three siblings with scleroderma (systemic sclerosis) and two with raynaud's phenomenon from a single kindred
Authors: Sheldon William B. , Lurie David P. , Maricq Hildegard R. , Bashar Kahaleh M. , Delustro Frank A. , Gibofsky Allan , Carwile Leroy E.
Published: February 2007

A kindred is reported which contains 3 siblings with scleroderma, 2 siblings with Raynaud's phenomenon, and 2 first‐degree relatives with histories suggestive of connective tissue syndromes. Studies of microvascular morphology and flow, serum endothelial cytotoxic activity, antinuclear antibodies, and HLA haplotypes in 18 relatives and 6 spouses revealed that 4 of 5 affected siblings expressed the HLA‐DRw4 antigen, which was also present in 2 of 3 asymptomatic relatives whose serum contained endothelial cytotoxic activity. The evidence for an inherited susceptibility to scleroderma is reviewed.
Proteoglycans from normal and degenerate cartilage of the adult human tibial plateau
Authors: Santer Vivien , White Robert J. , Roughley Peter J.
Published: February 2007

Proteoglycans were extracted from normal and degenerate cartilage of the human tibial plateau. Both areas possessed proteoglycans of similar chemical composition, though the degenerate cartilage contained a greater proportion of molecules of lower buoyant density and enriched in keratan sulfate. There was no evidence for the changes in glycosaminoglycan synthesis that have been described for clinically osteoarthritic cartilage, or for changes in the ability to aggregate with hyaluronic acid.
Effect of cyclophosphamide, hydrocortisone, and levamisole on collagen‐induced arthritis in rats
Authors: Stuart John M. , Myers Linda K. , Townes Alexander S. , Kang Andrew H.
Published: February 2007

The immune response of rats to type II collagen was modified by pretreating the rats with levamisole, hydrocortisone, or cyclophosphamide. Rats were observed for the development of collagen‐induced arthritis and were bled serially for the determination of antibody levels to type II collagen. Levamisole had a slight but not significant potentiating effect with arthritis developing earlier, whereas hydrocortisone and cyclophosphamide significantly depressed the incidence of arthritis; cyclophosphamide also delayed its onset. Antibody levels measured by radioimmunoassay paralleled the clinical course of arthritis.
Blind evaluation of the diagnostic specificity of nailfold capillary microscopy in the connective tissue diseases
Authors: Kenik Jay G. , Maricq Hildegard R. , Bole Giles G.
Published: February 2007

Twenty‐four patients with connective tissue diseases and 5 control subjects were studied by “wide‐field” photography. A total of 44 photographs of the nailfold were sent to the second author (HRM) for “blind” diagnostic interpretation. The scleroderma‐dermatomyositis pattern was identified in 17 of 18 photographs of 11 scleroderma patients, and 5 of 5 photographs of 2 dermatomyositis patients. Six of 8 photographs of 5 patients with systemic lupus erythematosus were correctly identified, as were 7 of 7 photographs of 5 control subjects. These results demonstrate that characteristic patterns of nailfold capillary abnormalities can be identified and correlated blindly with the clinical diagnosis in several connective tissue diseases.
Hla antigens in essential mixed cryoglobulinemia
Authors: Migliorini Paola , Bombardieri Stefano , Castellani Alberto , Ferrara Giovan Battista
Published: February 2007

HLA antigens were studied in 36 patients with essential mixed cryoglobulinemia. The antigens that showed the largest percentage of deviations from the control group were DRw3 (40% versus 20%), DRw8 (32% versus 11.5%), and Cw6 (5.6% versus 20.7%). None of these changes, however, was significant when the P values were corrected for the number of specificities scored for each locus. These data indicate that essential mixed cryoglobulinemia is not strongly associated with any of the HLA antigens serologically determined, but there was a suggestion that certain manifestations, particularly renal involvement, are related to a specific haplotype.
The role of histones as nuclear autoantigens in drug‐related lupus erythematosus
Authors: Tan Eng M. , Portanova Joseph P.
Published: February 2007

Patients with drug‐related lupus erythematosus produce antibodies to nuclear histones which can be detected by a three‐step indirect immunofluorescent technique. Procainamide‐related antinuclear antibodies were detected by this technique, but hydralazine‐related antinuclear antibodies were not. Certain evidence suggests that antibodies induced by the two drugs are reactive with different subclasses of histones. Hydralazine was shown to interact with a soluble DNA‐histone complex, and the resulting interaction rendered the histone moiety resistant to trypsin digestion. This mechanism may help to maintain DNA‐histone complexes in a potentially immunogenic form and result in the production of autoantibodies.
Urinary excretion of sialic acid‐containing saccharides in systemic lupus erythematosus
Authors: Maury C. Peter J. , Sjöblom Clara , Wegelius Otto
Published: February 2007

Urinary sialic acid‐containing trisaccharides, total sialic acid, and serum sialic acid were studied in 17 patients with systemic lupus erythematosus (SLE) and in 15 healthy controls. The urinary excretion of sialyllactose, measured by a gas chromatographic method, was significantly greater in patients with SLE (37.4 ± 21.4 mg/24 hours, SD) than in the control subjects (13.7 ± 3.8 mg/24 hours, P < 0.001). The mean excretion of sialyl‐N‐acctyllactosamine (16.6 ± 8.5 mg/24 hours) and total sialic acid (82.5 ± 29.4 mg/24 hours) was also greater in the SLE group than in the controls (8.7 ± 2.8 and 58.0 ± 16.0 mg/24 hours, respectively; P < 0.01). Serum levels of sialic acid were correspondingly higher in the SLE patients (84.4 ± 20.4 mg/100 ml) than in the controls (63.7 ± 6.5 mg/100 ml, P < 0.001). Urinary excretion of sialyl‐lactose correlated positively with clinical disease activity (P < 0.001) and with anti‐DNA antibody levels (P < 0.05). On the average, patients with moderate or severe disease excreted three times more sialyl‐lactose than did those with mild or inactive disease. Our results suggest that the excretion of sialyl‐oligosaccharides reflects disease activity in SLE.
Acetylator phenotype and metabolic disposition of isoniazid in japanese patients with systemic lupus erythematosus
Authors: Ishizaki Takashi , Horai Yukio , Koya Gyoichi , Matsuyama Kenji , Iguchi Sadao
Published: February 2007

Acetylator phenotype and metabolic disposition of isoniazid (INH) were studied in 19 Japanese (a population shown to be 11.5% slow acetylators) patients with spontaneous systemic lupus erythematosus (SLE) and 19 healthy controls. Subjects with the elimination half‐life (t1/2) of INH of 2.0 hours or less were considered rapid and those of 2.2 hours or more were slow acetylators. Results of phenotyping showed that 17 of 19 SLE patients were rapid, 1 slow, and 1 indeterminate, whereas 18 of the controls were rapid and 1 indeterminate. When phenotyped according to another reported antimode (107 or 110 minutes), 3 of the patients and 2 of the controls were slow and the remainder were all rapid acetylators. The distribution of INH t1/2, acetyl INH to INH ratios in urine and plasma, and hydrazine compounds in urine measured with gas chromatographymass spectrometry was similar between the two groups, except for 1 patient who was definitely classified as a slow acetylator. The relationship between phenotype distribution and possible pathoetiologic factors is discussed.
Cytotoxicity of anti‐fab antibodies against b lymphocytes in rheumatoid arthritis
Authors: Nasu Hajime , Chia David , Iwaki Yuichi , Barnett Eugene V. , Terasaki Paul I.
Published: February 2007

Anti‐Fab antibody titers were positive in 70% of rheumatoid arthritis patients (54 of 77) and 3% (1 of 35) of healthy donors. Their specificity was examined by inhibition of the radioimmunoassay for anti‐Fab antibodies, which demonstrated that they are against the Fd region of the intact immunoglobulin molecule. In addition, anti‐Fab antibodies have broad specificities for IgG antigens, shown by inhibition with myeloma IgG. They are cytotoxic against B (20% of B cells from most healthy donors) but not T lymphocytes, with cytotoxicity greater at 5°C than 37°C. These studies show that the anti‐Fab antibodies interact with allotypic or idiotypic determinants on subpopulations of B lymphocyte cell surface antigens.
The Influence of Fibronectin on Cryoprecipitate Formation in Rheumatoid Arthritis and Systemic Lupus Erythematosus
Authors: Beaulieu André D. , Valet Jean P. , Strevey Johanne
Published: February 2007

Fibronectin, a human fibroblast surface and plasma protein, is present in cryoprecipitates of synovial fluids and/or sera from patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and mixed essential cryoglobulinemia. Fibronectin was shown to be capable of influencing cryoprecipitate formation. No antibodies to fibronectin could be detected, thus ruling out the possibility that it was directly involved in the formation of cold‐insoluble antigen—antibody complexes. Fibrinogen or fibrinogen degradation products were frequently present in synovial fluid cryoprecipitates but rarely in serum cryoprecipitates. Since complexes of fibronectin—fibrin—fibrinogen are known to be cold‐insoluble, such interactions could occur in synovial fluids and contribute to the formation of cryoprecipitates. In serum, however, this is not likely to occur, and the mechanism by which fibronectin influences cryoprecipitate formation remains to be elucidated.
Abnormalities of Pulmonary Vascular Dynamics and Inflammation In Early Progressive Systemic Sclerosis
Authors: Furst Daniel E. , Davis James A. , Clements Phillip J. , Chopra Sawtantra K. , Theofilopoulos Argyrios N. , Chia David
Published: February 2007

Abnormalities of pulmonary function were studied in 10 patients with progressive systemic sclerosis (PSS) and 3 control subjects. All underwent 81M krypton lung scanning and total body gallium scanning. Immune complexes were measured by Raji cell radio–immunoassay and polyethylene glycol (PEG) assay. Perfusion scans were abnormal in 7 of 9 patients, and 5 of 9 showed a decrease in pulmonary perfusion after cold challenge. Increased gallium uptake was noted in the lungs of 6 of 9 patients. Krypton scans were normal in the control group. Elevated immune complexes were noted in 8 of 10 patients by the Raji assay and in 5 of 10 with the PEG assay. Efforts to separate patients with PSS into subgroups may lead to a better understanding of and advances in therapy for PSS.