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Biomedical subjects

G Solomon

Publications and source records attributed to G Solomon.

At least 73 records · Page 4Linked to original sources

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↗

Familial systemic lupus erythematosus. Presence of a cross-reactive idiotype in healthy family members.

Sera of 27 members of 3 human kindreds with familial systemic lupus erythematosus (SLE) were examined for expression of a cross-reactive idiotype present on anti-DNA antibodies of SLE patients. By radioimmunoassay, serum samples from 6 of 8 SLE patients and 15 of 19 family members had high-titered reactivity with the antiidiotype, 3I. Isoelectric focusing and Western blot analysis of 3I-reactive bands revealed two patterns of reactivity: either a pattern of bands present at pH 5-7, or bands present at pH 5-7 with additional bands present at pH 7-8.5. Cationic bands were found to correlate with the presence of anti-DNA antibodies, indicating that immunoglobulin charge may be a factor in determining specificity for DNA. Millipore filter analysis revealed anti-DNA antibodies in sera of 4 of 8 SLE patients and 2 of 19 family members without SLE. In 2 additional SLE patients and 2 additional family members, anti-DNA antibodies were revealed when sera were analyzed under conditions that dissociate immune complexes. This study indicates that expression of an idiotype associated with anti-DNA antibodies is significantly increased in relatives of SLE patients and usually occurs in the absence of anti-DNA activity.

Antibodies, Antinuclear↗

Detection of masked anti-DNA antibodies in lupus sera by a monoclonal anti-idiotype.

We report here the use of a monoclonal anti-idiotype 3I to human anti-DNA antibodies to detect in serum idiotype-positive antigen-binding antibodies lacking DNA-binding activity as measured by conventional antigen binding assays. We studied paired serum samples from 13 patients with systemic lupus obtained at two times in the course of their disease: in each patient, one serum sample has anti-DNA activity and the second serum sample has no anti-dsDNA activity detectable by Millipore filter, ELISA, or Crithidia assay. Reactivity with 3I as detected with a radioimmunoassay (RIA) was present in all 13 sera with anti-dsDNA activity. Six patients showed a decrease in 3I reactivity to normal levels in the second serum sample, in which anti-dsDNA antibodies were not detectable by conventional antigen-binding assays. The other seven patients' second serum sample continued to show elevated 3I reactivity by RIA even though no anti-dsDNA activity was apparent. When the 3I-reactive antibodies from these latter patients' sera were eluted from a 3I affinity column, they revealed DNA-binding activity. Furthermore, dsDNA binding by these sera was apparent when they were displayed on Western blots of isoelectric focusing gels run in 8 M urea and incubated with radiolabeled dsDNA. These results indicate that the 3I anti-idiotype can detect anti-DNA antibodies in some sera of SLE patients that lack anti-DNA activity by ordinary assays. These antibodies may be inhibited in binding dsDNA by excess antigen or autologous anti-idiotype, and their DNA binding activity can be unmasked by procedures promoting immune complex dissociation.

Antibodies, Anti-Idiotypic↗

Spontaneous hypoglycemic seizures in pregnancy. A manifestation of panhypopituitarism.

A 32-year-old woman had seizures and coma due to severe hypoglycemia (26 mg/dL) in the 32nd week of an otherwise uncomplicated pregnancy. She responded dramatically to the administration of cortisol. Initial endocrine evaluation disclosed prolactin (PRL), corticotropin, and thyrotropin (TSH) deficiencies. The patient recovered completely with cortisol and thyroid hormone therapy and was delivered of a healthy male child at term. Endocrine reevaluations one week and six months postpartum disclosed luteinizing hormone, follicle-stimulating hormone, growth hormone, PRL, corticotropin, and probable TSH deficiencies. The cause of this panhypopituitarism has not been determined. This case suggests that the appropriate initial treatment for spontaneous symptomatic hypoglycemia in pregnancy, while awaiting further endocrine evaluation, is the administration of cortisol.

Adult↗

Use of monoclonal antibodies to identify shared idiotypes on human antibodies to native DNA from patients with systemic lupus erythematosus.

Antinative DNA antibodies were purified from the serum of a patient with active systemic lupus erythematosus. Using hybridoma technology, we produced several mouse monoclonal antibodies directed against idiotypic determinants on these antinative DNA antibodies. One of these monoclonal anti-idiotypic antibodies, 3I, an IgG2a Kappa, was extensively characterized. 3I is believed to be directed against an idiotypic determinant because (i) its reactivity with antinative DNA antibodies is not inhibited by a large excess of pooled human serum, (ii) it reacts with F(ab')2 fragments of antinative DNA antibodies, and (iii) it reacts with antinative DNA antibodies of all IgG subclasses. 3I is not directed against the antigen binding site in that native DNA and 3I do not compete for binding to antinative DNA antibodies. Eight of nine sera containing antinative DNA activity as determined by the Millipore filter assay reacted with 3I in a solid-phase radioimmunoassay. These findings suggest that antinative DNA antibodies from nonrelated patients with systemic lupus erythematosus share a common idiotype.

Antibodies, Anti-Idiotypic↗

Tetanus prophylaxis and accidental wounds.

Of 400 consecutive patients who had wounds treated in the Accident Department, 200 remembered receiving either booster injections or a full course of tetanus toxoid in the last 10 years. During this period, 182 patients received their initial toxoid injection in association with treatment of a wound in an accident department. Only 71 (38%) of these patients attended for a full course of injections. From our assessment of the wounds and the patient's anti-tetanus immunity, 79 patients (20%) were considered to be at risk of developing tetanus. By further considering the time interval elapsed between injury and treatment, a 'high risk' group of 13 patients (3%) was recognised. It is recommended that the use of human immunoglobulin should be reserved for the 'high risk' group, and that the remainder of the 'at-risk' patients should receive penicillin prophylaxis only.

Adolescent↗

Carbamazepine in difficult to control epileptic out-patients.

Twenty-three difficult to control patients with 1 or more seizures per week despite diphenylhydantoin (DPH), phenobarbital and/or primidone in near and toxic doses and blood levels were entered in the study. 3 had grand mal. 8 psychomotor seizures and 12 had both. During a 6 1/2 month study period the patient received active drug and placebo for 3 months each; randomized, double-blind. The dose was to be increased within 4 weeks up to 6 capsules per day equal to 1,200 mg of carbamazepine (C), while the doses or previously taken (basis) anticonvulsants were to remain unchanged. Hematopoetic system and heptic functions were monitored. Complete seizure control attributable to C was not achieved in any, but up to 50% improvement occurred in 12 patients. Questionable improvement was thought to take place in 3 patients, no change occurred in 7, and psychomotor seizures became more frequent in 1 patient. A clear-cut psychotropic effect was not observed. Adverse effects attributable to C were a decline of WBC below 4,000 with relative neutropenia in 3 patients followed by at return to the previous after discontinuation of C. Nystagmus and unsteadiness were seen in about half of the patients, and some headache and drowsiness occurred in one quarter. The highest C blood level was 11.8 mug/ml, the lowest 3.8 mug/ml (average 5.6 mug/ml) during 1,200 mg intake. It seemed, generally, that intoxication occurred with lower blood levels of carbamazepine in those patients whose basis anticonvulsant blood levels were highest.

Adolescent↗

Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant growth in neuroblastoma cell lines.

The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB) cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR).

Animals↗