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Biomedical subjects

R Segal

Publications and source records attributed to R Segal.

At least 19 recordsLinked to original sources

The influence of aging on the induction and manifestations of experimental systemic lupus erythematosus.

The influence of age on autoimmunity was studied in a model in which experimental systemic lupus erythematosus (SLE) is induced in normal mice by the injection of a human monoclonal anti-DNA antibody expressing a common idiotype designated 16/6 Id. The resulting disease is expressed by the production of a variety of autoantibodies and clinical manifestations characteristic to human SLE. Female BALB/c mice, at ages of 2 and 12 months, were immunized with the 16/6 Id. Mice were tested periodically for the presence of autoantibodies. The production of all autoantibodies tested was significantly lower in the older mice as compared to the group of young mice. Clinical manifestations which included leukopenia, increased erythrocyte sedimentation rate and proteinuria were similar in both age groups. Kidney evaluations revealed differences among the two groups of mice. While in all kidney sections of young mice multiple immune complex deposits were detected, in the group of older mice half had similar pathology while the rest either were negative or had only segmental and partial glomerular immune complex depositions. Thus, aging is associated with a decrease in the capacity to respond to the pathogenic anti-DNA, 16/6 Id, by the production of antibodies and autoantibodies and in the expression of a milder disease.

Aging

Induction of experimental systemic lupus erythematosus (SLE) in mice with severe combined immunodeficiency (SCID).

A model in which experimental SLE is induced in normal mice by the injection of a human anti-DNA MoAb expressing a common idiotype 16/6 Id has been established in our laboratory. In the present study we have attempted the induction of experimental SLE in mice with SCID by the transfer of lymphocytes obtained from mice with experimental SLE. Disease could not be induced by direct immunization of SCID mice with the 16/6 Id nor by transfusion of normal splenocytes and immunization with the 16/6 Id thereafter. In contrast, disease was induced in SCID mice which were transplanted with splenic lymphocytes obtained from SLE afflicted BALB/c mice. The disease was expressed by the presence of high titres of antibodies and glomerular immune complex deposits were present in the kidney sections of these mice. Mice that received spleen cells from donors with experimental SLE together with the 16/6 Id developed higher titres of autoantibodies and had, in addition to the immune complex deposits, glomerular histological pathology. The model of experimental SLE induction in SCID mice should help in the elucidation of the role of different cell types in the pathogenesis of SLE.

Animals

Increased incidence of urinary tract infection in patients with rheumatoid arthritis and secondary Sjögren's syndrome.

The incidence of lower urinary tract infection in 120 women with rheumatoid arthritis and secondary Sjögren's syndrome was evaluated retrospectively. Thirty one patients (26%) had secondary Sjögren's syndrome. Recurrent urinary tract infection was significantly more common in these patients (11/31) than in patients without Sjögren's syndrome (4/89). Habitual leucocyturia was also more common in patients with secondary Sjögren's syndrome (18/31) than in patients with rheumatoid arthritis without Sjögren's syndrome (8/89). Of seven patients with vaginal sicca symptoms, six had recurrent urinary tract infection. Urinary 24 hour mucopolysaccharide excretion in 20 patients with Sjögren's syndrome was similar to the excretion in 10 patients without Sjögren's syndrome. These results show that recurrent urinary tract infection is significantly more common in women with rheumatoid arthritis and secondary Sjögren's syndrome. A local deficit in protective urinary mucosal secretion or other immune mechanisms may be responsible for this susceptibility.

Adult

Tortuous peripheral arteries: a cause of focal neuropathy. Case report.

Segmental ulnar neuropathy has been reported as a result of ulnar nerve compression due to posttraumatic false aneurysms of the ulnar artery and, more infrequently, due to thrombosis or true aneurysms of the same vessel. The authors present a case of segmental sensory ulnar neuropathy in the wrist which intraoperatively demonstrated impingement on the ulnar nerve by a tortuous ulnar artery. The symptomatic relief and electrophysiological improvement that occurred immediately following neurovascular decompression confirm that the vascular anomaly was the cause of neuropathy. Pulsatile pressure applied to the nerve trunk may have triggered ectopic stimulation of sensory fibers manifested by a tingling and burning sensation. There was immediate resolution of paresthesia following mobilization of the impinging vessel from the nerve. Subsequent rapid electrophysiological recovery may be explained by improvement in focal nerve microcirculation following vascular decompression. Tortuosity (megadolichoectatic anomaly) of intracranial arteries has been related to cranial nerve or brain-stem dysfunction; however, this appears to be the first report in the literature of a case in which such association has been found to occur extracranially, involving a peripheral nerve.

Arm

Treatment with bifonazole shampoo for seborrhea and seborrheic dermatitis: a randomized, double-blind study.

Forty-four patients with seborrhea and seborrheic dermatitis of the scalp were treated with either bifonazole shampoo (22 patients) or the vehicle shampoo (22 patients) in a randomized, double-blind vehicle-controlled study. The patients were instructed to wash their scalps 3 times weekly for 6 weeks and were examined every 3 weeks. Responses were evaluated by clinicians using a clinical grading of scaling, erythema and overall improvement, and also by the patients, who assessed pruritus and overall improvement, using a scale of 0 to 3. The improvement following the bifonazole shampoo was found to be significantly greater than that achieved with the vehicle shampoo in regard to the clinical evaluation of scaling (p = 0.01) as well as patient evaluation of pruritus (p = 0.008) and overall improvement (p = 0.03). No major adverse side effects were recorded.

Adolescent

[Mycetoma with black granules: first case in a native of Israel].

We present a case of black grain mycetoma caused by Madurella mycetomatis. The diagnosis was made on the basis of conventional light microscopy and mycological studies. After 12 months of oral therapy with ketoconazole, the patient showed partial response. This is the first native Israeli case of black grain mycetoma.

Adult

A novel 21-kDa protein as a serum marker for benign and malignant urogenital tumors: preliminary communication.

A novel 21-kDa protein (p21) was isolated from auto-immune complexes, found in sera of 14 patients with malignant urogenital tumors and isolated on Protein A-Sepharose. Isolated complexes were analyzed in 15% polyacrylamide-SDS minigels. After staining with Coomassie blue R, the bands were scanned with a clinical densitometer. The level of p21 in sera of cancer patients was 3 times higher than that found in normal individuals. An attempt was made to correlate consecutive levels of p21 in the sera of these cancer patients with the clinical course. In 4 cases a significant decrease (57-75%) in the level of p21 was observed in parallel with response to treatment. In 9 of 10 cases where no response or tumor progression was observed, the relative abundance of p21 increased or remained unchanged. Thus, the level of p21 was indicative of progression or regression of the disease in 13 out of 14 patients. Similar high levels of p21 in sera were also found in 22 patients with benign hyperplasia of prostate. The p21 protein was not immunoreactive with known anti-ras antibodies such as Y13-259, 142-24E05 and anti-rap1. Partial amino acid analysis of this protein showed no complete homology to any known protein, but a partial homology to known bacterial proteins involved in DNA replication or transcription was observed. Monitoring of the novel p21 levels before and after treatment may be useful in follow-up of cancer patients, providing evidence of response to treatment.

Adult

Promoter activity and distance constraints of one versus two Sp1 binding sites.

In the simple adenovirus 2 early 1B (E1B) promoter, moving the single Sp1 transcription factor binding site (GC box) from its wild-type position eight base pairs (bp) from the TATA box to 30 bp upstream is equivalent to its deletion (Wu, L., and Berk, A. (1988) Genes & Dev. 2, 403-411). In more complex promoters, multiple upstream elements regulate transcription over greater distances. To understand these spacing constraints, we placed two GC boxes in phase at various distances from the E1B TATA box. Whereas one GC box at eight bp from TATA increases transcription in vivo 5-fold compared with TATA alone (Wu, L., Rosser, D. S. E., Schmidt, M. C., and Berk, A. (1987) Nature 326, 512-515), two GC boxes increased in vivo transcription 25-30-fold. Transcriptional stimulation by two GC boxes fell off rapidly in vivo at 30 bp from TATA, remained approximately constant through 50 bp, then decreased again at 70 bp. Consequently, two GC boxes have a multiplicative effect at eight bp from TATA and continue to stimulate transcription at a greater distance from TATA than a single Sp1 site. Quantitatively different results were observed for in vitro transcription using a nuclear extract; a more linear fall off with increasing distance from TATA was observed. Separating the two GC boxes progressively decreased transcription. E1A stimulation of these promoters in vivo indicates that Sp1 transcription control is independent of E1A transactivation.

Adenoviridae

[Sulfasalazine in rheumatoid arthritis].

Sulfasalazine (SLZ) is now a second-line treatment in rheumatoid arthritis (RA), as well as in psoriatic arthritis and ankylosing spondylitis. 54 patients with active RA were treated with enteric coated SLZ (2 g daily) in a 24-week open study. Clinical and laboratory parameters of disease activity were monitored initially and thereafter at 2-week intervals for the first 2 months, and then at 4-week intervals until the end of the 24-week study. There was significant clinical improvement at the end, as shown by scores for joint pain (Ritchie), grip strength and morning stiffness (p less than 0.0001, less than 0.0001 and less than 0.01, respectively, by paired t test). Clinical improvement was accompanied by significant decrease in erythrocyte sedimentation rate and increase in hemoglobin (p less than 0.002 and less than 0.016, respectively). There was improvement in some cases as early as 3 weeks after starting therapy. The drop-out rate was significant: 19/54 (35%), most (13) due to side-effects, mainly gastrointestinal; none of the side-effects were serious. Our results, similar to those of other studies, indicate that despite the high rate of side effects, SLZ is an effective, second-line drug for RA.

Arthritis, Rheumatoid

A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

Alleles

Familial erythema nodosum.

Erythema nodosum (EN) is a hypersensitivity reaction associated with many diseases. We describe a family in which 4 sisters had acute or recurrent EN. HLA typing showed a common haplotype in the affected members of the family. A review of familial EN and HLA distribution in EN is presented.

Acute Disease

The use of visible light-cured resin system in maxillofacial prosthetics and neuro-orthopedic surgery.

The use of visible light-cured (VLC) resin was evaluated in contrast to more traditional chemical-cured resins for reconstruction of the spine in experimental rats. Such procedures are used to reconstruct vertebra in humans following corpectomy for neoplastic destruction of the spine. Numerous disadvantages exist in the use of chemical-cured resins, including excessive heat generated during the polymerization, cytotoxic effects of the nonpolymerized monomers on adjacent tissues, increased risk of infection due to impaired immunity, and distortion problems with the polymers. A new visible light-cured resin, Triad, was tested for use in maxillofacial prosthetics and for vertebral body replacement in neuro-orthopedic surgery. This study evaluated the biocompatibility of the VLC resin system as a bone implant material. The results of this study have shown the VLC resins underwent polymerization without substantial exothermic reaction and the biologic testing indicated that they are nontoxic and biocompatible. Some of the advantages noticed by using VLC resin are accuracy of fit and ease of fabrication and manipulation.

Acrylic Resins

Herniated L4-L5 disc after placement of Harrington instrumentation for a fracture of the thoracolumbar spine.

The authors report a case in which L5 radiculopathy developed acutely after surgery for placement of Harrington rod instrumentation for an L1 body fracture. Computed tomographic myelography demonstrated a large L4-L5 herniated disc that had not been present in preoperative studies. An emergency laminectomy was performed, and a large, free, subligamentous disc fragment was removed. The patient subsequently regained L5 sensorimotor function. The postoperative development of lumbar radiculopathy is an uncommon complication of Harrington rod instrumentation that may result from several biomechanical features of the instrumentation. These injuries may not be detected by intraoperative monitoring of somatosensory evoked potentials, and therefore, the postoperative neurological examination assumes a crucial role in the early diagnosis of these lesions. As our case demonstrates, these radicular deficits may be reversible if their cause is promptly recognized and treated.

Aged

The use of visible light-curing resin for vertebral body replacement.

The technology of visible light-curing resin has recently been developed for use in removable prosthodontics. A quartz halogen lamp producing a 400- to 500-nanometer wave-length spectrum of visible light is used to polymerize high-molecular-weight acrylic resin monomers. While several in vitro and in vivo studies of visible light-curing resin are found in the dental literature, no studies have yet been performed to evaluate it as an intracorporeal implant in surgery. The authors have designed a rat model of microcervical corpectomy to assess vertebral body replacement with visible light-curing resin in comparison to conventional autopolymerizing methyl methacrylate. Spinal cord function tests, spinal-implant stability assessments, and histological evaluations were made in a total of 41 rats at 2, 4, or 6 months postimplant. No animal developed a neurological deficit or radiographic instability, and at sacrifice there was no evidence of implant fracture-extrusion. In addition, there were no signs of adverse reaction in the surrounding tissues. Morphological investigation of the resin/bone interface at 6 months revealed very good implant anchorage. Visible light-curing resin was found to be far superior to methyl methacrylate for construction of spinal implants. Its waxy consistency makes it easy to handle. It remains pliable until light is applied, allowing adjustments in shape for a well-fitted implant without time constraints. Applied in layers, adjustments can be made even after polymerization of a previous layer. This new implantable resin will allow safer, immediate stabilization in patients with neoplastic destruction of the spine, and may also be advantageous for other neurosurgical applications, such as cranioplasty.

Animals

Assessment and treatment of a pediatric patient in chronic care: ethnographic methods applied to occupational therapy practice.

Ethnographic methods were used to examine how an experienced occupational therapist assesses and treats a pediatric patient within a relatively long-term clinical relationship. Treatment goals for this preverbal child with Hirschsprung disease, who began occupational therapy at 22 months of age, included (a) introduction of oral feeding to reduce dependence on total parenteral nutrition through intravenous feeding and (b) facilitation of exploratory play, which had been developmentally delayed during extensive periods of immobilization during medical care. This article shows how the meaning of therapeutic activities changes for the patient over time, as the occupational therapist builds trust through affect attunement, validates his or her empathic interpretations, and develops common understandings with the patient's family and others within the social and cultural contexts of chronic care.

Activities of Daily Living

Regulatory T cell activity specific to human type II and III collagens in rheumatoid arthritis.

Fifty-one patients with rheumatoid arthritis (RA) were examined for their immune response potential to human collagen type II and III. It was found that T cells of 57% of patients with RA proliferated to collagen type III whereas only 27% of T cells of patients with osteoarthritis (OA) and healthy controls responded to this antigen by proliferation (p less than 0.04). A lower percentage (38%) of patients with RA had proliferative responses to collagen type II in comparison to 17% of responders in healthy controls. The capability to produce T cell helper factors specific to collagen type III was found to be significantly higher in patients treated with nonsteroidal antiinflammatory drugs (NSAID) (60%) in comparison to patients with OA (16%) and healthy controls (13%). Immunoregulatory drugs affected the specific T helper function in response to collagen type III but did not change the proliferative responses to collagen type II and III in patients with RA. HLA analyses revealed a significant difference in the frequency of HLA-DRw10 between our sample of patients with RA and healthy controls.

Antibody Formation

Effect of spa therapy in Tiberias on patients with rheumatoid arthritis and osteoarthritis.

Forty-one patients with rheumatoid arthritis were treated for 2 weeks at a Tiberias spa hotel. Randomized into 2 groups, Group 1 received a combination of mineral baths and mud packs, and Group 2 had tap water baths only. Both groups had a significant but temporary improvement in Ritchie index. Group 1 showed a significant improvement in grip strength. No improvement was noticed in morning stiffness, 15 meter walk time and laboratory variables of disease activity in either group. Twelve patients with osteoarthritis (OA) received 2 weeks of treatment with mineral baths and mud packs. Statistically significant improvement for a period of 6 months was noticed in night pain, pain on passive motion, tenderness on palpation and in the index of severity of OA of the knee.

Arthritis, Rheumatoid

Rescue of interleukin-1 activity by leucovorin following inhibition by methotrexate in a murine in vitro system.

We have recently shown that methotrexate (MTX) inhibits interleukin-1 (IL-1) activity in vitro. This effect may play an important role in the rapid antiinflammatory action of MTX in rheumatoid arthritis. In the present study, we showed that the inhibition of IL-1 activity in vitro by MTX is dependent on folate pathways since, after the addition of leucovorin, the inhibitory effect of MTX was abolished. These findings may shed more light on the mechanism of action of MTX in rheumatoid arthritis. They also point to the fact that some IL-1 activities may be dependent on intracellular folate pathways.

Animals