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Biomedical subjects

A Solomon

Publications and source records attributed to A Solomon.

At least 109 records · Page 6Linked to original sources
PubMed1997

Treatment of inflamed pterygium and pinguecula with topical indomethacin 0.1% solution.

PURPOSE: To evaluate the effect of topical indomethacin 0.1% on signs and symptoms in inflamed pterygium and pinguecula. METHODS: Fifty-one consecutive patients who had inflamed pterygium (n = 32) or pinguecula (n = 19) were studied in a randomized, double-masked, controlled way. Objective signs (conjunctival congestion, redness, edema, and staining of cornea) and subjective complaints (photophobia, pain, foreign-body sensation, discomfort, and tearing) were evaluated and scored. In addition, we evaluated total signs, total symptoms, and total score. Group 1 (n = 25) received topical indomethacin 0.1% solution and group 2 (n = 26) received a placebo six times daily for 3 days, then four times daily for 11 days. Patients were examined before and at days 3, 7, and 14 after the treatment began. RESULTS: In group 1 at day 3, the scores of total signs, total symptoms, and total score decreased (p = 0.001), and they further decreased after 14 days (p = 0.02 to p = 0.05). In group 2 at day 3 these parameters also significantly decreased (p = 0.01 to p = 0.02), but no further improvement occurred after 14 days. Comparing groups 1 and 2 revealed a decrease in scores in group 1 for total signs, total symptoms, and total score at days 3, 7, and 14 (p = 0.03 to p = 0.002) except for total signs after 14 days (p = NS). All the patients reported mild stinging for < 1 min after administration of the drops. CONCLUSIONS: This study indicates that topical indomethacin solution 0.1% is a useful treatment for inflamed pterygium and pinguecula.

Administration, Topical↗
PubMed1996

Repertoire cloning of lupus anti-DNA autoantibodies.

To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-double-stranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These included a V(H)5 autoantibody from the affected twin, that has a targeted cluster of mutations that potentially improves binding affinity. The recovered IgG anti-dsDNA autoantibodies expressed the same idiotypes associated with the in vivo IgG anti-dsDNA response of the respective SLE donor. Heavy-light chain shuffling experiments demonstrated a case in which the in vitro creation of anti-dsDNA binding activity required restrictive pairing of a heavy chain with Vlambda light chains similar to those in circulating anti-dsDNA autoantibodies. By contrast, IgG anti-ds autoantibodies could not be recovered from the library from the healthy twin, or from shuffled libraries with heavy chains from the healthy twin. These repertoire analyses illustrate how inheritance and somatic processes interplay to produce lupus-associated IgG autoantibodies.

Amino Acid Sequence↗
PubMed1996

Characterization of a light chain product of the human JC lambda 7 gene complex.

The human light chain JC lambda locus is comprised of seven distinct segments, designated JC lambda 1, JC lambda 2, JC lambda 3, JC lambda 4, JC lambda 5, JC lambda 6, and JC lambda 7. Whereas three of these seven represent pseudogenes (psi Clambda 4, psi C lambda 5, and psi C lambda 6), the JC lambda 1, JC lambda 2, and JC lambda 3 complexes are functional, as demonstrated by the finding of their protein products through sequence analyses of lambda-type Bence Jones proteins and light chains derived from monoclonal Igs. Although the JC lambda 7 segment also appears functional, as evidenced through analysis of lymphocyte-derived mRNA, heretofore no monoclonal JC lambda 7-containing lambda-chains have been identified. Serologically, two distinct isotypic markers, Mcg and Oz, are associated, respectively, with JC lambda 1 and JC lambda 3 proteins, in contrast to JC lambda2 components, which do not express these determinants and represent a third isotype. Although another serologic marker, Ke (Kern), considered a fourth isotype, has been assigned to the JC lambda 7 complex, this relationship has been questioned. We now report the primary structural features of a lambda-type Bence Jones protein that include the four distinctive residues encoded by the JC lambda 7 gene segment. This protein, obtained from a patient with multiple myeloma and designated MCP, represents the first example of such a molecule and provides definitive evidence that the JC lambda 7 gene complex is functional. Additionally, comparison of the C lambda sequences of Mcg-/Oz- Bence Jones proteins MCP and KERN supports the contention that the Ke-associated one-residue amino acid variation at position 152 reflects a C lambda A2 polymorphism and that yet another isotypic marker, provisionally designated Mcp, is encoded by the JC lambda 7 gene segment. Thus, we posit that there are four human JC lambda isotypes, Mcg, Ke-Oz-/Ke+Oz-, Ke-Oz+, and Mcp, that represent, respectively, products of the JC lambda 1, JC lambda 2, JC lambda 3, and JC lambda 7 gene complexes.

Adult↗
PubMed1996

Pitfalls of molecular replacement: the structure determination of an immunoglobulin light-chain dimer.

The structure of protein Cle, a human light-chain dimer from the lambdaIII subgroup, was determined using 2.6 A data; the R value is 18.4%. The structure was solved, after a false start, by molecular replacement with the lambdaII/V Mcg protein as a search structure. When the refinement did not proceed beyond an R value of 27%, it was discovered that while the constant domains were in their correct positions in the unit cell, the incorrect variable domains were used for defining the molecule. The correct solution required a rotation of 180 degrees around the local twofold axis that relates the two constant domains of the dimer. The correct variable domain positions overlap about 70% of the same volume as the incorrect ones of a symmetry-related molecule. The refinement distorted the geometries of the domains. Though the constant domains were in their correct positions, the r.m.s. (root-mean-square) deviation of the Calpha atom position was 1.2 A when the two constant domains were compared. For the correct structure, this value is 0.5 A. The phi and psi angles, the r.m.s. chiral value and the free R value, even when calculated a posteriori, were good indicators of the correctness of the structure. The quaternary structure of the Cle molecule is similar to that in Mcg (crystallized from ammonium sulfate); the elbow bend is 115 degrees. However, the arrangement of the variable domains differs from that observed in other variable domain dimers. The variable domains of Cle are 0.7 A closer than in Mcg or variable dimer Rei. The hydrogen bonding at the interface of the two domains is novel. Residues Tyr36 from both monomers form a hydrogen bond that is part of a network with the Gln89 residues from both monomers. For the first time hydrogen bonds were observed between the main-chain peptide N and O atoms of the complementarity-determining region CDR2 and CDR3 segments of both monomers.

Journal Article↗
PubMed1996

Involvement of wound-associated factors in rat brain astrocyte migratory response to axonal injury: in vitro simulation.

The poor ability of mammalian central nervous system (CNS) axons to regenerate has been attributed, in part, to astrocyte behavior after axonal injury. This behavior is manifested by the limited ability of astrocytes to migrate and thus repopulate the injury site. Here, the migratory behavior of astrocytes in response to injury of CNS axons in vivo was simulated in vitro using a scratch-wounded astrocytic monolayer and soluble substances derived from injured rat optic nerves. The soluble substances, applied to the scratch-wounded astrocytes, blocked their migration whereas some known wound-associated factors such as transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and heparin-binding epidermal growth factor in combination with insulin-like growth factor-1 (HB-EGF + IGF-1) stimulated intensive migration with consequent closure of the wound. Migration was not dominated by proliferating cells. Both bFGF and HB-EGF + IGF-1, but not TGF-beta 1, could overcome the blocking effect of the optic nerve-derived substances on astrocyte migration. The induced migration appeared to involve proteoglycans. It is suggestive that appropriate choice of growth factors at the appropriate postinjury period may compensate for the endogenous deficiency in glial supportive factors and/or presence of glial inhibitory factors in the CNS.

Animals↗
PubMed1996

Efficacy of iontophoresis in the rat cornea.

BACKGROUND: Iontophoresis can enhance penetration of drugs into tissues. We examined the extent of penetration of gentamicin into the cornea of rats during iontophoresis and the effect of varying the concentrations of gentamicin, the duration of iontophoresis and the current densities during iontophoresis. METHODS: Eight groups of rats underwent corneal iontophoresis using gentamicin dissolved in agar. Low and high concentrations of gentamicin were used, as well as low and high current densities and long and short durations of iontophoresis. Control groups received topical or subconjunctival gentamicin, topical saline solution and mock iontophoresis with the agar-gentamicin mixture. The Mann-Whitney test was used for statistical evaluation. RESULTS: Highly bactericidal concentrations of gentamicin were obtained in all the iontophoresis-treated corneas. The high concentration compared to the low concentration of gentamicin in agar significantly increased the concentration of gentamicin in the corneas, as did the longer duration of iontophoresis. However, higher current intensity did not significantly enhance the drug concentration in the cornea. CONCLUSION: Iontophoresis with a concentrated gentamicin-agar mixture may provide a rapid increase of gentamicin levels in the cornea.

Absorption↗
PubMed1996

The influence of aestivation in land snails on the larval development of Muellerius cf. capillaris (Metastrongyloidea: Protostrongylidae).

The larval development of Muellerius cf. capillaris in aestivating Trochoidea seetzenii and Theba pisana was delayed: in the first snail 82% of the parasites remained as second-stage larvae (L2) after as much as 90 days, and in the second snail 60% remained as L2 after 50 days. Reactivation of T. seetzenii after 59 days of aestivation caused the larvae to develop to the third stage (L3). The number of recovered larvae among T. seetzenii was consistently higher in active vs aestivating snails (P < 0.05). Such differences were not evident among T. pisana (P > 0.05). In active T. pisana, larval development was faster than in active T. seetzenii, whereas there were no such differences between aestivating snails of these 2 species. Aestivating infected T. seetzenii had lower body weights than same-size active non-infected, as well as infected snails. Aestivating infected T. pisana were not weighed, but they too exhibited poor body condition.

Analysis of Variance↗
PubMed1996

Bilateral simultaneous corneal graft rejection after influenza vaccination.

PURPOSE: To treat a patient with bilateral simultaneous corneal graft rejection after influenza vaccination. METHODS: The patient received topical, subconjunctival, and systemic corticosteroids. RESULTS: The corneal grafts cleared after administration of corticosteroids. CONCLUSION: Ophthalmologists should be aware of the possibility of corneal graft rejection after influenza vaccination.

Administration, Topical↗
PubMed1996

The suitability of Trochoidea seetzenii of different ages as snail intermediate hosts of Muellerius cf. capillaris (Nematoda:Protostrongylidae).

Larval development of Muellerius cf. capillaris in small (1st-year juveniles, shell diameter 0.96 +/- 0.05 cm) and medium-size (2nd-year juveniles, 1.27 +/- 0.06 cm) Trochoidea seetzenii land snails was significantly more rapid than in large adult snails (1.96 +/- 0.09 cm). Only 9% of the inoculated 1st-stage larvae (400 +/- 20 per snail) were recovered from the large snails as compared to 25% from the medium and small snails. Of the exposed small snails, however, only 35% survived to the end of the experiment (33 days post-infection) as compared to a 97.5% and 98% survival rates for the same period in the medium and large adult snails, respectively.

Animals↗
PubMed1996

Vinblastine toxicity to the ocular surface.

Local ocular exposure to antineoplastic drugs occurs either during regular use of some of these drugs in ophthalmology or accidentally during the general use of these drugs. Many ocular side effects have been described after such intentional or accidental exposures. We describe a case of accidental ocular trauma by vinblastine. As in one of the only two previously published cases of ocular trauma by vinblastine, our patient showed acute keratopathy with a drop in visual acuity followed by the development of dry eyes and a subepithelial corneal scar. In addition, in an attempt to further evaluate the clinical course and the benefits of steroid treatment, nine rabbits were studied after ocular instillation of vinblastine. After the trauma, local steroid treatment was given in one eye of each rabbit; the second eye served as a control. The animal studies showed acute conjunctivitis and keratopathy with increasing severity in the first days and improvement thereafter. That course was similar to the one manifested in our patient. Local steroid treatment in the rabbit eye had no effect as compared with the control group. A possible mechanism for the induction of dry eyes is discussed.

Accidents, Occupational↗
PubMed1996

Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report.

A new vaccine against hepatitis B virus (HBV) infection, produced in mammalian Chinese hamster ovary (CHO) cells, contains the small(s), middle (Pre S2) and large (Pre S1) surface proteins of HBV. Three injections of a 5-micrograms or 10-micrograms dose were administered intramuscularly (i.m.) at 0, 1 and 6 months to a group of 105 young adults, who were monitored for a period of 6 months after the third injection. Seroconversion rates were 100% after the second injection of the 5-micrograms or 10-micrograms dose. Geometric mean titres of HBsAb at 1 month after the third injection were 12,156 mIU ml-1 and 13,482 mIU ml-1 in those receiving the 5-micrograms and 10-micrograms dose respectively. The vaccine was well tolerated with no significant adverse events. These preliminary results suggest that the Pre S-s recombinant vaccine, produced in mammalian cells, is highly immunogenic, leading to 100% seroconversion in the population tested after injection of only two doses of 5 micrograms.

Adolescent↗
PubMed1996

Potential treatment modalities for glaucomatous neuropathy: neuroprotection and neuroregeneration.

PURPOSE: This article presents the rationale and an experimental strategy for the development of new treatment modalities for glaucomatous neuropathy. Accumulating evidence suggests that regardless of the primary trigger of the retinal and optic nerve damage in glaucoma, the disease will continue to progress even when the cause is removed. The resulting damage can be mimicked by the progression of damage secondary to an acute partial crush injury at the optic nerve head. Such secondary damage includes degeneration of the directly injured optic nerve fibers culminating in death of their cell bodies, as well as degeneration of nerve fibers that escaped acute injury but nevertheless deteriorate as a result of their exposure to injury-induced mediators of secondary degeneration released by the directly affected neurons. CONCLUSION: We therefore propose that substances found to be effective in rescuing fibers from secondary degeneration and in increasing the survival rate or prolonging survival of retinal ganglion cells in the partially lesioned optic nerve may be useful for the treatment of glaucoma. The new approach does not replace hypotensive therapy, but addresses the glaucoma-induced damage by promoting nerve protection and neuroregeneration.

Animals↗
PubMed1995

Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients.

A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.

Adult↗
PubMed1995

Natural catalytic antibodies: peptide-hydrolyzing activities of Bence Jones proteins and VL fragment.

Monoclonal human light chains, i.e. Bence Jones proteins, and their recombinant variable fragments (VL) were screened for proteolytic activity using peptide-methylcoumarinamide (peptide-MCA) conjugates and vasoactive intestinal polypeptide (VIP) as substrates. Sixteen of 21 Bence Jones proteins and one of three VL fragments were capable of detectable cleavage of one or more substrates. The magnitude and kinetic characteristics of the activity varied with different substrates. Among the peptide-MCA substrates, the presence of tripeptide or tetrapeptide moieties with a basic residue at the scissile bond generally favored expression of the activity. The influence of N-terminal flanking residue recognition was evident from differing values of Km and kcat (turnover number) observed using different Arg-containing peptide-MCA substrates. Different light chains displayed different kinetic parameters for the same substrate, suggesting unique catalytic sites. Hydrolysis of VIP was characterized by nanomolar Michaelis-Menten constants (Km), suggesting comparatively high affinity recognition of this peptide. The 25-kDa monomer and the 50-kDa dimer forms of one light chain preparation were resolved by gel filtration in 6 M guanidine hydrochloride. Following renaturation, the monomer displayed 51-fold greater peptide-MCA-hydrolyzing activity than the dimer. A renatured VL domain prepared by gel filtration in 6 M guanidine hydrochloride displayed VIP-hydrolyzing activity in the 12.5-kDa peak fractions. These results provide evidence for the proteolytic activity of certain human light chains and imply that this phenomenon may have a pathophysiological significance.

Amino Acid Sequence↗