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Biomedical subjects

G Solomon

Publications and source records attributed to G Solomon.

At least 19 recordsLinked to original sources

Identification of a novel reductase in folate metabolism.

A protein with a molecular weight of 27,500 was co-purified with the enzyme dihydrofolate reductase (molecular weight 22,000) from the liver of mice less than 8 weeks of age using a methotrexate-Sepharose affinity matrix. This 27.5 kDa protein crossreacts with dihydrofolate reductase against an antiserum raised to the purified 22 kDa enzyme. The protein could also reduce dihydrofolate to tetrahydrofolate, thus demonstrating the catalytic properties of dihydrofolate reductase. The expression of this 27.5 kDa protein also appears to be age-dependent because it could not be isolated from liver of mice older than four months.

Aging

An approach to the human immunodeficiency virus-positive patient with a spondyloarthropathic disease.

One of the unanticipated consequences of infection with the human immunodeficiency virus (HIV) is the appearance of various rheumatic syndromes that traditionally have been thought to result from inappropriate overactivity of the immune system. This distinctive spectrum of rheumatic syndromes has been well described; however, the therapeutics and specific patient management as well as the significance of these disorders for diagnostic classification of the rheumatic disorders have not received a great degree of attention. This article focuses on these areas with emphasis on (1) the nosology of the arthrocutaneous musculoskeletal syndromes with HIV, (2) clinical presentation of the various syndromes, (3) current concepts regarding the etiopathogenesis of the spondyloarthropathic form of arthritis in this setting, and (4) an approach to therapy.

Anti-Inflammatory Agents

Neurophysiological abnormalities in adolescents with type I Crigler-Najjar syndrome.

We report neurophysiological abnormalities in two adolescents with type I Crigler-Najjar syndrome, an autosomal recessive disorder characterized by severe unconjugated hyperbilirubinemia. Electroencephalograms (EEGs) demonstrated frequent generalized single and polyspikes, and background slowing. Normal pattern reversal evoked responses (PRVERs) and normal central brain-stem auditory evoked responses (BAERs) were recorded in both patients. These findings differ from the EEG triphasic wave pattern seen in the EEG in hepatic encephalopathy and the central BAER abnormalities seen in many infants with kernicterus. Thus these findings most likely result from complex multifactorial processes and are not simply the result of the hyperbilirubinemia which is common to all 3 conditions.

Acoustic Stimulation

Combination D-penicillamine and methotrexate therapy: proposal for early and aggressive treatment for rheumatoid arthritis.

We report a retrospective study of 16 patients with seropositive rheumatoid arthritis who were placed on combination D-penicillamine and methotrexate therapy for a period of 5-86 months. Three patients were lost to follow-up, and one patient died of unknown causes at another institution. Among the 12 remaining patients, there was no withdrawal secondary to drug intolerance. All patients demonstrated improvement in functional class correlated with a reduction in joint count, duration of morning stiffness, erythrocyte sedimentation rate, rheumatoid factor, and prednisone requirement. Eight of the 12 patients achieved remission as defined by the American College of Rheumatology criteria. Remission was sustained for a period of 3-72 months. The dosage of D-penicillamine ranged from 250-1000 mg/d (mean = 750 mg); that of methotrexate ranged from 5-15 mg/week (mean = 10 mg). The study indicates that D-penicillamine and methotrexate combination therapy is effective in the treatment of severe rheumatoid arthritis and warrants further prospective investigation.

Adult

A novel association of DQ alpha and DQ beta genes in the DRw10 haplotype. Determination of a DQw1 specificity by the DQ beta-chain.

The association of the class II genes of the DRw10 haplotype from a cell line, NASC, initiated from a member of a well characterized family, was analyzed by sequencing cDNA clones corresponding to DR beta I, DQ alpha, and DQ beta genes. An identical haplotype was also identified in the Raji cell line. In addition to typing as DRw10 and DQw1 with HLA typing sera both, the NASC and Raji cell lines were shown to react strongly with the monoclonal antibodies 109d6 (specific for DRw10 beta 1 and DRw53 beta 2 gene products) and Genox 3.5.3 (specific for DQw1) and exhibited the restriction fragment length polymorphism indicative of a DRw10, DQw1 haplotype. The DR beta 1 gene corresponding to the DRw10 specificity was found to have a first domain sequence different from all other DR beta I genes. Sequence analysis of the 3'-untranslated region of this DR beta-chain gene showed a significant divergence from the 3' untranslated region of the DRw53 family of haplotypes and a lesser divergence from that of the DRw52 and DR1/DR2 families. The sequence of the DQ beta genes corresponding to the DQw1 specificity in the DRw10 haplotype was found to be identical to the DQ beta gene from a DR1, DQw1 haplotype. Surprisingly, however, the DQ alpha gene did not resemble other DQw1-like DQ alpha genes, but was identical in sequence to the DQ alpha gene found in DR4 haplotypes. The novel association of DQ alpha and DQ beta genes in the DRw10 haplotype revealed in these studies may result from a double recombinational event. More consequentially, these studies strongly suggest that the DQw1 specificity recognized by Genox 3.5.3 is determined by the DQ beta chain and is not affected by the DQ alpha-chain.

Amino Acid Sequence

Aspects of the spectrum, prevalence and disease susceptibility determinants of Reiter's syndrome and related disorders associated with HIV infection.

Arthrocutaneous disorders including Reiter's syndrome, psoriasiform rashes, and other forms of chronic arthritis and enthesopathy, such as psoriatic arthritis, occur with an increased prevalence in the setting of HIV infection. Herein we describe the spectrum and prevalence of musculoskeletal and allied skin disorders as they occur in the setting of HIV infection. The role of genetic susceptibility in the development of these disorders is addressed. Based on the frequency of infectious agents capable of triggering reactive arthritis and the presence of HLA-B27 in 71% of these individuals, it is suggested that the disorder strongly resembles Reiter's syndrome as it occurs in the not HIV-infected group. Preliminary evidence indicates an enhanced penetrance for susceptibility among HLA-B27 individuals. In contrast, among HIV-infected patients with psoriasiform lesions there was no statistically significant association (P less than 0.05) between the presence of psoriasiform rash and the HLA alleles Cw6, B7, B17, Bw16, or Bw57 when compared with HIV-infected controls. These findings suggest that among HIV-infected individuals the development of Reiter's syndrome involves an immune recognition event primarily dependent upon HLA-B27 molecules in which an unknown antigen in the context of HLA-B27 is presented to CD8 lineage suppressor/cytotoxic cells. In contrast, the pathogenesis of psoriasiform lesions in HIV patients, despite their similarity to certain lesions in Reiter's syndrome, proceeds by distinct pathways that do not involve events influenced by specific polymorphic class I molecules.

Arthritis, Psoriatic

Arthritis associated with HIV infection: radiographic manifestations.

Radiographs of symptomatic joints were retrospectively evaluated in 24 patients with inflammatory arthritis and human immunodeficiency virus (HIV) infection. Clinically, 20 patients had a seronegative arthritis including Reiter syndrome (54%), psoriatic arthritis (17%), and undifferentiated forms of spondyloarthropathy (13%). These patients were indistinguishable radiographically from patients with typical seronegative disorders except for the predominance of lower-extremity abnormalities. Four patients (17%) had a rheumatoidlike arthritis defined as acute symmetric polyarthritis (ASP). With the exception of extensive proliferative periostitis, ASP simulated classic rheumatoid arthritis. HIV-associated arthritis was manifest during various stages of HIV infection. It preceded acquired immunodeficiency syndrome in 64% of patients with stage IV HIV infection. Awareness of the coexistence of HIV infection in patients with the above-mentioned arthritides is important, since immunosuppressive therapy, commonly used in the treatment of arthritis, can have detrimental effects in patients with HIV infection.

Acquired Immunodeficiency Syndrome

Posterior tibial tendon dysfunction: its association with seronegative inflammatory disease.

Idiopathic inflammation and rupture of the posterior tibial tendon (PTT) has received much attention in the recent literature. In this report of the presentation of PTT dysfunction as a manifestation of seronegative inflammatory disease, we describe the clinical and laboratory features of 76 patients with inflammation and/or rupture of the PTT. Analysis of all patients identified two discrete groups. Group A patients were younger (mean age 39 years) and had multiple manifestations of inflammation at other sites of ligament and tendon attachments (enthesopathy). Other features of a systemic inflammatory disorder such as oral ulcers, conjunctivitis, colitis, and especially psoriasis were common in the latter patients and their families. Group B consisted predominantly of elderly patients (mean age 64 years) with isolated dysfunction of the PTT. These two groups differed widely in the manner of clinical presentation, demographic data, family history, HLA data, and surgical pathology. These distinctions suggest different pathogeneses for posterior tibial tendinitis. Group A demonstrated local manifestations of a systemic inflammatory disease, whereas group B exhibited the effects of mechanical trauma and degeneration.

Adolescent

Implications from the occurrence of Reiter's syndrome and related disorders in association with advanced HIV infection.

Information bearing on the prevalence and character of Reiter's syndrome and allied disorders as they occur in a setting of HIV infection was reviewed. Based on the frequency of infections by organisms capable of inducing reactive arthritis and the presence of HLA-B27 in 71% of the individuals, it was concluded that the disorder strongly resembled Reiter's syndrome occurring in the non-HIV infected group. Preliminary evidence suggested an enhanced penetrance of susceptibility among HLA-B27 individuals. In view of the preservation of CD8 lineage T cells and functional loss of CD4 lineage T cells in HIV-infected patients, it was suggested that a specific immune recognition event is at the center of the pathogenesis of this syndrome which involves preservation of an unknown antigen in the context of HLA-B27 to CD8 lineage suppressor/cytotoxic T cells.

Acquired Immunodeficiency Syndrome

The co-occurrence of Reiter's syndrome and acquired immunodeficiency.

Thirteen patients who had the co-occurrence of severe Reiter's syndrome and the acquired immunodeficiency syndrome (AIDS) or its syndromes were studied. The arthritis was reactive in three patients and without defined cause in the others. Nine patients had HLA-B27. The two syndromes appeared simultaneously in four patients, suggesting a common biologic process, and in the others the immunodeficiency either preceded or followed the arthritis. Reiter's syndrome occurring in the setting of this profound immunodeficiency suggests that helper T cells were not involved in the pathogenesis of the rheumatic disease. Difficulties were encountered in the diagnosis of either syndrome in the presence of the other. Two patients with Reiter's syndrome developed Kaposi's sarcoma and fulminant AIDS after receiving methotrexate, which emphasizes the need for caution in the use of immunosuppressive therapy in Reiter's syndrome. An additional patient with undifferentiated spondylarthropathy subsequently developed psoriasis in conjunction with the onset of AIDS.

AIDS-Related Complex

Epileptic facial metamorphopsia.

A 14-year-old patient with a right parietal arteriovenous malformation presented with seizures characterized by metamorphopsia of faces. Unlike adults with right hemisphere pathology she performed like an age matched control on a task requiring recognition of unfamiliar faces. This likely reflects maturational changes in hemispheric dominance for face recognition.

Adolescent