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Biomedical subjects

A Solomon

Publications and source records attributed to A Solomon.

At least 145 records · Page 8Linked to original sources
PubMed1994

Preferential expression of human lambda-light-chain variable-region subgroups in multiple myeloma, AL amyloidosis, and Waldenström's macroglobulinemia.

We have compared the distribution of lambda-light-chain variable-region (V lambda) subgroups among Ig lambda molecules found in the serum of normal individuals with that of monoclonal Ig lambda components obtained from patients with plasma cell and related immunoproliferative disorders. A panel of monoclonal antibodies specific for each of the major human V lambda subgroups--V lambda I, V lambda II, V lambda III, V lambda IV, V lambda VI, and V lambda VIII--was used in a highly sensitive enzyme-linked immunosorbent assay (ELISA) to quantitate each of these populations. The mean distribution of Ig lambda I, Ig lambda II, Ig lambda III, Ig lambda IV, Ig lambda VI, and Ig lambda VIII molecules in serum specimens collected from 20 normal adults was approximately 40, 3, 43, 5, 5, and 3% of the total Ig lambda population, respectively. In contrast, that of monoclonal IgG, IgA, and IgD proteins and Bence Jones proteins obtained from patients with multiple myeloma and related gammopathies (n = 196) was approximately 27, 28, 39, 5, 0, and 1%, respectively. The percentage of monoclonal Ig lambda II components found in individuals with AL lambda amyloidosis (n = 41) was comparably increased to that seen in multiple myeloma and was even higher in patients with Waldenström's macroglobulinemia (n = 16), in whom 63% of the IgM lambda proteins were of the V lambda II subgroup. Also evidenced were differences in the distribution of other V lambda subgroups in the disease states: Most striking was the predominance (41%) of the V lambda VI subgroup among monoclonal lambda chains obtained from patients with AL amyloidosis and that this subgroup was found exclusively on amyloidosis-associated proteins. No Ig lambda VI-type myeloma- or macroglobulinemia-related proteins were identified. The observed alterations in V lambda subgroup distribution among "pathologic" monoclonal Igs were attributed to the particular disease and not related to the heavy-chain class. Our finding that certain V lambda subgroups are nonstochastically expressed in lambda-type multiple myeloma, AL amyloidosis, and Waldenström's macroglobulinemia provides evidence for abnormal VL gene usage in these disorders and, thus, furnishes new insight into their pathogenesis.

Amyloid↗
PubMed1994

Cytokines modulate the inflammatory response and change permissiveness to neuronal adhesion in injured mammalian central nervous system.

Axonal injury of peripheral nerves has been shown to be followed by rapid and massive invasion of the nerves by macrophages, which appear to play an important role in the subsequent ability of these nerves to regenerate. In contrast, macrophage invasion of injured nerves of the central nervous system is limited, and the relationship between the post-traumatic inflammatory response of central nervous system nerves and their poor ability to regenerate is not fully understood. We used the proinflammatory cytokine tumor necrosis factor-alpha and the macrophage growth factor, colony stimulating factor-1, to examine whether the inflammatory response can be augmented in the optic nerve following injury, and whether such augmentation is accompanied by regeneration-associated changes. It appeared that the two cytokines caused a significant increase in the number of macrophages invading the optic nerve immediately after injury. Interestingly, however, in the nerve treated with tumor necrosis factor-alpha (but not in the nerve treated with colony stimulating factor-1) this increase was accompanied by an increased permissiveness of the nerve to neuronal adhesion, which we examined in vitro using longitudinal sections of the nerve on which PC12 cells were seeded. The results are discussed with respect to the ability of tumor necrosis factor-alpha to modify the nonpermissive nature of central nervous system white matter.

Animals↗
PubMed1994

Identification and characterization of a functional human Ig V lambda VI germline gene.

We have isolated from a human genomic library a potentially functional and distinctive germline gene, designated IGLV6S1, that encodes for light chains of the V lambda VI subgroup. An identical germline gene was cloned from fibroblasts obtained from a patient with light-chain-associated amyloidosis (AL amyloidosis) whose serum and urine contained, respectively, a monoclonal IgG lambda VI protein and a lambda VI Bence Jones protein. Isolation and characterization of cDNA cloned from the patient's bone marrow-derived monoclonal plasma cells revealed that the nucleotide and predicted protein sequences of the rearranged gene were approximately 95% and approximately 90% homologous to those of the germline gene, respectively. The finding that the transcriptional start site for lambda VI RNA synthesis was located upstream of the putative TATA-box promoter, rather than downstream as found for the V lambda II subgroup, implies that a different transcriptional machinery controls the expression of the human V lambda VI-gene family.

Amino Acid Sequence↗
PubMed1994

Evaluation of asymptomatic subjects with low forced expiratory ratios (FEV1/VC).

BACKGROUND: Heightened bronchial hyperreactivity is frequently associated with airflow limitation, atopy, or cigarette smoking. The purpose of this study was to evaluate healthy subjects with significantly low values of forced expiratory volume in one second/vital capacity % (FEV1/VC%) by measuring their airway response to exercise and methacholine challenge, compared with a control group with normal spirometric values. METHODS: Eighty four healthy subjects with significantly low flow rates (group A, FEV1/VC% < 2 SD% predicted) were evaluated and compared with 37 subjects with normal flow rates (group B). Static lung volumes, spirometric tests, exercise, and methacholine challenges were performed. RESULTS: Lung volumes were normal for both groups. Mean FEV1/VC% was 69% for group A and 82% for the control group. Salbutamol improved baseline FEV1 in eight subjects in group A (mean 15%), while methacholine induced a drop in FEV1 in 12 subjects. The dose-response curve to methacholine reached a plateau in all the responders. None of the subjects in the control group improved their baseline FEV1/VC% to salbutamol, but three showed bronchial hyperreactivity similar to those in group A. CONCLUSIONS: Bronchial hyperreactivity does not occur more often in asymptomatic subjects with mildly low FEV1/VC% so these subjects do not require special investigations for airway disease.

Adolescent↗
PubMed1994

Characterization of a novel interleukin-6 autocrine-dependent human plasma cell line.

A new human monoclonal plasma cell line, designated UTMC-2, was established from the pleural effusion of a patient with immunoglobulin (Ig)A kappa-related multiple myeloma. The cultured cells were Epstein-Barr virus-negative and exhibited the morphological and ultrastructural features characteristic of plasma cells. Immunohistochemical analyses revealed the presence of cytoplasmic IgA kappa as well as the plasma cell-associated surface antigens CD38 and CD56. Other B-cell markers, including CD10, CD19, CD20, and HLA-DR, were absent. The UTMC-2 cells were interleukin (IL)-6 responsive: Co-culture with IL-6 increased IgA kappa synthesis and cell proliferation in a dose-dependent manner. In contrast, an IL-6 antisense oligonucleotide had an opposite effect. Although the UTMC-2 cells expressed IL-6 mRNA (as demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR)) and contained IL-6, the concentration of this cytokine in cell culture supernatants was less than that detectable by the enzyme-linked immunosorbent assay (ELISA) employed (i.e. <3 pg/ml). Further, cell growth was not inhibited by polyclonal or monoclonal anti-IL-6 antibodies. Flow cytometric analysis revealed that IL-6 receptors present on the surface of the UTMC-2 cells were not saturated with endogenous IL-6. Taken together, these results indicate that, in this human plasma cell line, IL-6 functions uniquely in an intracellular autocrine fashion to enhance Ig synthesis and cell growth. In this respect, the UTMC-2 cells represent a novel resource for further study of the role of IL-6 in the pathogenesis of multiple myeloma.

ADP-ribosyl Cyclase↗
PubMed1993

Axonal regeneration is associated with glial migration: comparison between the injured optic nerves of fish and rats.

The central nervous systems of mammals and fish differ significantly in their ability to regenerate. Central nervous system axons in the fish readily regenerate after injury, while in mammals they begin to elongate but their growth is aborted at the site of injury, an area previously shown to contain no glial cells. In the present study we compared the ability of glial cells to migrate and thus to repopulate the injured area in fish and rats, and used light and electron microscopy in an attempt to correlate such migration with the ability of axons to traverse this area. One week after the optic nerve was crushed, both axonal and glial responses to injury were similar in fish and rat. In both species glial cells were absent in the injured area (indicated by the disappearance of glial fibrillary acidic protein and vimentin immunoreactive cells from the site of injury in rat and fish, respectively), while at the same time axonal growth, indicated by expression of the growth-associated protein GAP-43, was restricted to the proximal part of the nerve. In fish, 2 weeks after the crush, GAP-43 staining (i.e., growing axons) was seen at the site of injury, in association with migrating vimentin-positive glial cells. One week later the site of injury in the fish optic nerve was repopulated by vimentin-positive glial cells, and GAP-43-positive axons had already traversed the site of injury and reached the distal part of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Dose and temporal parameters in delaying injured optic nerve degeneration by low-energy laser irradiation.

Low-energy laser irradiation has been reported to postpone the degenerative processes in crushed optic nerves of rats, which are part of the nonregenerable mammalian central nervous system. In the present study, we evaluated the optimal irradiation parameters for this purpose. Optic nerves of 141 rats were subjected to crush injury and then irradiated through the eye, starting at different points of time before or after the injury, for different durations and periods, using various intensities of either helium-neon laser or noncoherent infrared light (904 nm). The effect was evaluated by measurements of the compound action potentials of the nerve segments between the site of injury and the optic chiasm. The compound action potential amplitude of the crushed nonirradiated nerves, as measured 2 weeks after the injury, was found to be 0.51 +/- 0.30 mV, in contrast to 3.10 +/- 1.03 mV measured in 232 normal nerves. Irradiation with a 10.5 mW helium-neon laser for 2 and 3 min once a day for 14 consecutive days resulted in maximal preservation of action potentials (1.78 +/- 0.72 and 1.95 +/- 0.71 mV, respectively). Irradiations beginning immediately prior to the injury were as effective as irradiations beginning soon after it. Irradiations for longer than 3 min or twice a day aggravated the damage. Noncoherent infrared light was ineffective or adversely affected the injured nerves. Our experiments suggest that optimal delay of posttraumatic optic nerve degeneration in rats is attainable with 10.5 mW helium-neon laser irradiations for 2 or 3 min once a day for 14 consecutive days.

Action Potentials↗
PubMed1993

Mite asthma in childhood: a study of the relationship between exposure to house dust mites and disease activity.

BACKGROUND: Children with asthma are commonly sensitized to the house dust mite. METHODS: We took monthly measurements from July to December of the amount of mites in the mattresses of asthmatic children and correlated them with symptom score, pulmonary function, and airway hyperreactivity to methacholine. RESULTS: In spite of the high number of Dermatophagoides pteronyssinus throughout this period, symptom and treatment scores, as well as PC20 to methacholine, worsened during the months of September and October. CONCLUSIONS: It is concluded that when asthmatic children allergic to mites are exposed to high levels of mite allergen, the number of mites in the mattress dust no longer correlate with increased symptoms, and that other factors are more likely to be associated with exacerbation.

Adolescent↗
PubMed1993

Conformational dependency of human IgG heavy chain-associated Gm allotypes.

Human IgG allotypic markers Gm(a)[Glm(1)], Gm(x)[Glm(2)]; Gm(f)[Glm(4)], Gm(b)[G3m(5) and (11)] and Gm(g)[G3m(21)] were studied after chemical modification of IgG histidines by diethylpyrocarbonate, tyrosines by N-acetylimidazole and lysines by formaldehyde and sodium borohydride. Degrees of substitution were estimated by trinitrobenzenesulfonic acid assay. IgG of known Gm phenotype isolated from serum of hyperimmune anti-tetanus toxoid donors was studied. Histidyl modification resulted in virtually complete loss of Gm(a) and Gm(g) antigenicity but preservation of Gm(x), Gm(b) and Gm(f). Reconstitution of the histidyl residues using hydroxylamine resulted in virtually complete restoration of Gm(a) and Gm(g) antigenicity. Histidine modification resulted in no significant decrease in ELISA anti-tetanus antibody activity. Alteration of tyrosyl residues using N-acetylimidazole considerably diminished Gm(a) and Gm(f) expression. This effect was reversed by hydroxylamine treatment. Moreover, chemical alteration of tyrosyl residues produced a complete loss of Gm(g) antigenicity which was only partially restored after deacylation. A urinary H chain fragment containing the VH region directly linked to C gamma 3 which contained the Gm(a) specific and Gm(x) specific amino acid residues was positive for Gm(a) but negative for Gm(x). Another urinary H chain fragment containing only the C gamma 3 domain was negative for both Gm(a) and (x). These findings indicate that Gm allotypic markers may depend on conformational determinants in which strongest expression for Gm(a) and (x) depends on structures expressed by C gamma 3 linked to C gamma 2 domains. Although RFs react with the region encompassing the C gamma 2-C gamma 3 interface, Gm-specificities of such reactions are affected allosterically through single or double amino acid substitutions at a relatively distant site.

Amino Acid Sequence↗
PubMed1993

Novel immunization protocol and ELISA screening methods used to obtain and characterize monoclonal antibodies specific for human light chain variable-region subgroups.

We have developed a novel immunization protocol for the production of a panel of high-affinity murine monoclonal antibodies (MoAbs) that are specific for each of the major human kappa and lambda light chain variable-region (VL) subgroups. Mice were injected with heat-precipitated human Bence Jones proteins or VL-related fragments emulsified in monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) at two- to four-week intervals over a seven-month period. A unique direct capturing enzyme-linked immunosorbent assay (ELISA) employing biotinylated monoclonal light chains was designed to select optimally immunized animals for hybridoma preparation and to screen culture supernatants for high-affinity anti-VL MoAbs. These methods have led to the generation of MoAbs that by ELISA react specifically with each of the four V kappa subgroups--V kappa I, V kappa II, V kappa III, and V kappa IV or five V lambda subgroups--V lambda I, V lambda II/V, V lambda III, V lambda IV, and V lambda VI. These reagents have been used successfully to establish, on the basis of VL subgroup, the monoclonal nature of serum or urinary immunoglobulins as well as those found in the cytoplasm or on the cell surface of monoclonal plasma cell or B-lymphocyte populations, respectively. The availability of anti-VL subgroup-specific MoAbs will facilitate the immunodiagnosis and study of patients with multiple myeloma, AL amyloidosis, and related B-cell proliferative disorders.

Amyloidosis↗
PubMed1993

Production and immunodiagnostic applications of antihuman light chain monoclonal antibodies.

Hybridomas producing antihuman light chain monoclonal antibodies (MoAbs) were derived from fusion of SP2/O mouse myeloma cells with splenic lymphocytes from mice repeatedly immunized with purified kappa- and lambda-type Bence Jones proteins representative of the major V kappa (V kappa I, V kappa II, V kappa III, V kappa IV) and V lambda (V lambda I, V lambda II/V, V lambda III, V lambda IV, V lambda VI) subgroups or gene families. Monoclonal antibodies were obtained that had specificity for constant-region (CL) determinants common to all kappa or lambda light chains (C kappa and C lambda, respectively) as well as for variable-region (VL) epitopes unique to each of the V kappa or V lambda subgroups. The capability of these reagents to recognize CL and VL determinants on monoclonal immunoglobulin (Ig) molecules was demonstrated in fluid-phase antigen-capturing enzyme-linked immunosorbent assay (ELISA), solid-phase ELISA, and immunoblotting. In addition, these antilight chain MoAbs were used to establish immunocytochemically the kappa or lambda type and VL-subgroup nature of light chains expressed by the cytoplasmic Ig of monoclonal plasma cell and surface Ig of B-lymphocyte populations, respectively. These antibodies facilitated the immunohistochemical detection and characterization of light-chain-associated amyloid (AL amyloid) and other types of light-chain-related tissue deposits. Furthermore, the anti-CL-specific MoAbs were used to measure serum and urinary Ig kappa and Ig lambda concentrations. Quantification of Bence Jones protein excretion, even in the presence of other urinary proteins, was possible using the highly sensitive anti-C kappa and anti-C lambda MoAbs reactive only with free light chains. The ability to identify and characterize, through the use of these antihuman light chain MoAbs, light-chain-related epitopes at the protein, cellular, and tissue level has clinical importance in the diagnosis and treatment of patients with monoclonal plasma cell and related B-cell immunoproliferative diseases.

Amyloidosis↗
PubMed1993

Internal sclerostomy using laser ablation of dyed sclera in glaucoma patients: a pilot study.

Twelve eyes of 12 patients with refractory glaucoma were treated with internal sclerostomy using laser ablation of dyed sclera. The technique involves iontophoretic impregnation of the sclera at the limbal region with 1% methylene blue and subsequent delivery of a pulsed dye laser beam to the stained area through a goniolens. The red wavelength of 664 nm generated by the laser is maximally absorbed by the stained sclera and creates a through and through sclerostomy. Successful complete sclerostomy was achieved in seven eyes (58.3%) but there was some reduction of intraocular pressure (IOP) in all cases. Mean prelaser IOP (of all 12 eyes) was 36.6 mm Hg and 1 hour after therapy it was reduced to 20.0 mm Hg. At the end of the follow-up period (mean 16 months) the mean IOP was 23.7 mm Hg; five eyes (41%) maintained their IOP below 22 mm Hg, and the average number of medications per eye came down from 3.25 to 2.25 per eye. Transient corneal burns with Descemet's membrane folds adjacent to the laser impact zone were detected in eight eyes (67%). No major complications like IOP spike, hyphaema, iridodialysis, or retinal detachment have been detected. Clear cornea and dark blue scleral staining are essential for the mechanical success of this procedure. Gonioscopic laser internal sclerostomy of methylene blue dyed sclera is technically feasible and the preliminary results of IOP control in refractory glaucoma are promising. Modifications of the iontophoresis process and laser parameters are currently under investigation in order to improve these results.

Adult↗
PubMed1993

Postexercise syncope: evidence for increased activity of the sympathetic nervous system.

This report describes an association of postexertional syncope with increased levels of circulating catecholamines. A 36-year-old male who experienced postexercise bradycardia and asystole had higher basal plasma norepinephrine (120 versus 68 +/- 6 pg/ml) and epinephrine (18 versus less than 10 pg/ml) but a similar vagal tone (vagal tone index of 5.44 versus 5.81 +/- 1.00 U) when compared with 6 closely matched subjects who underwent an uneventful stress test.

Adult↗
PubMed1992

Horseradish peroxidase labeling of growth cones and axons beyond the site of injury in injured rabbit optic nerve axons growing in their own environment.

Spontaneous growth of injured axons in the mammalian central nervous system is limited. We have previously shown an apparently regenerative growth of injured optic axons in the adult rabbit, achieved by supplying them with soluble substances originating from growing axons, followed by low energy helium-neon laser irradiation. The growing unmyelinated and thinly myelinated axons were embedded in astrocytes, and some were in the process of remyelination by oligodendrocytes. They were shown to have originated from the retinal ganglion cells. The present study further supports evidence relating to the origin and nature of these axons. Light microscopic analysis of these axons labeled with anterogradely transported horseradish peroxidase revealed that many of these axons have varicosities and bear growth cone-like swellings in their tips. These axons traverse the lesion site and extend into the distal stump in a disorganized pattern.

Animals↗
PubMed1992

Protein L from Peptostreptococcus magnus binds to the kappa light chain variable domain.

Protein L is an immunoglobulin light chain-binding protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus. The major variable region subgroups of human kappa and lambda light chains were tested for protein L binding; V kappa I, V kappa III, and V kappa IV bound protein L, whereas no binding occurred with proteins of the V kappa II subgroup or with any lambda light chain subgroups. Studies of the protein L binding capacity of naturally occurring VL fragments, and VL- and CL-related trypsin- and pepsin-derived peptides prepared from a kappa I light chain, localized the site of interaction to the VL domain. The affinity constant for the binding to an isolated V kappa I fragment was comparable to that for the native protein (Ka 0.9 x 10(9) M-1 and Ka 1.5 x 10(9) M-1, respectively). No binding occurred with CL-related fragments. Extensive reduction and alkylation of the V kappa fragment or the native kappa chain resulted in complete loss of protein L binding. Although it is possible, from comparative amino acid sequence data, to identify certain VL-framework region residues that account for the selective binding of protein L by kappa I, kappa III, and kappa IV proteins, our studies indicate that this interaction is essentially dependent upon the tertiary structural integrity of the kappa chain VL domain.

Amino Acid Sequence↗
PubMed1992

Patulous rectum extension into the ischiorectal fossa: CT findings.

Protrusion of the rectum with egress into the ischiorectal fossa was present on computed tomography (CT) in three elderly women. CT demonstration of such rectal redundancy in elderly women will avoid unnecessary bowel damage in the case of misguided clinical assessment of rectal pathology.

Aged↗