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Biomedical subjects

A Solomon

Publications and source records attributed to A Solomon.

At least 73 records · Page 4Linked to original sources
PubMed1999

In vitro immunoglobulin light chain fibrillogenesis.

These techniques permit the production of bulk quantities of fibrils and provide methods for monitoring the kinetics of fibrillogenesis. Experiments performed in the fluorimeter require low protein concentrations, sampling is not necessary (with ThT in situ), and the measured fluorescence signal is indicative of fibril content and is not complicated by the presence of amorphous aggregates. However, ASF using the orbital shaker is a simple, rapid, initial procedure, adequate for screening for fibrillogenic potential, in which multiple experiments can be performed simultaneously and over long periods of incubation. These methods may be used to investigate the fibrillogenesis of VL proteins and BJps as a means of predicting pathogenicity, as well as providing information on the basic biophysical principles underlying light chain aggregation.

Amino Acid Sequence↗
PubMed1999

Desiccation tolerance of Muellerius capillaris first-stage larvae from Israeli arid and French temperate habitats and their compatibility to the land snail Theba pisana.

The survival capacities of Muellerius capillaris (Nematoda: Protostrongylidae) free-living larval stages (L1) of an Israeli desert isolate (Nubian isolate) (92 mm rain per annum) and a French isolate from a temperate habitat (650 mm rain per annum) were compared under humid and extreme dry conditions. Under the dry conditions (7% relative humidity [r.h.] and 33% r.h. at 23 degrees C), both isolates exhibited the same remarkable survival capacity for periods of 17 and 28 days, respectively (> 92% survival, P > 0.1). However, during and after recovery from the anhydrobiotic state, different behaviour patterns of L1 were observed in each isolate. Under humid conditions (97% r.h.) for 10 days, both isolates exhibited similarly low survival percentages (13.4 +/- 4.6%, S.E., survival for the Nubian isolate, 3 +/- 3% for the French isolate, P > 0.05). In water, the French isolate was less active, survived better (52 +/- 8.4% vs 28.7 +/- 3.7, by day 28, P < 0.05) and retained a better morphological appearance (shrunk less) than the Nubian isolate. Larval development of the French isolate in the land snail Theba pisana was significantly faster than that of the Nubian isolate, reaching a higher proportion of infective stages (L3) on day 36 post-infection (78.6% vs 56% P > 0.05). However, similar infection intensities were recovered in snails infected with either of the isolates (59.8 +/- 10.3, S.E., n = 14, for the French isolate, 53 +/- 6, n = 13, for the Nubian isolate, P < 0.05).

Animals↗
PubMed1999

The distribution of gentamicin in the rabbit cornea following iontophoresis to the central cornea.

The purpose of this study was to evaluate the penetration of gentamicin into the central, midperipheral and peripheral cornea of rabbits following iontophoresis to the central 3 mm of the cornea. Four groups (groups 1-4) of five rabbits (one eye per rabbit) underwent corneal iontophoresis using gentamicin dissolved in agar. Low (1 mg/ml) and high (10 mg/ml) concentrations of gentamicin in agar were used for one or ten minutes. Two control groups (groups 5 and 6) of five eyes each underwent mock iontophoresis with low and high concentrations of agar-gentamicin mixture. Following sacrifice of the rabbits, the central, midperipheral and peripheral parts of each cornea were excised. Gentamicin concentration was determined in each part of every cornea. High concentrations of gentamicin (951.6 +/- 369.4 microg/ml to 26.6 +/- 41.34 microg/ml) were obtained in the central parts of all the iontophoresis-treated corneas. In each group, except group 6, central corneas had higher concentrations of gentamicin compared to midperipheral corneas (p = 0.038 to p = 0.021), and midperipheral corneas had higher levels than peripheral corneas (p = 0.038 to p = 0.021). Following iontophoresis, gentamicin is found in all portions of the corneas; however, the highest concentration of the drug remains in the central cornea.

Analysis of Variance↗
PubMed1999

Late-onset, bleb-associated endophthalmitis following glaucoma filtering surgery with or without antifibrotic agents.

The use of adjunctive antimetabolites such as 5-fluorouracil (5-FU) and mitomycin C (MMC) in trabeculectomy has caused an increased concern as to the risk of bleb-associated endophthalmitis. In this study, we compared the incidence of this complication between different methods of adjunctive treatment in glaucoma filtering surgery. Records of 15 cases of late-onset, bleb-associated endophthalmitis which were admitted to the Ophthalmology Department, Hadassah University Hospital, between January 1980 and December 1997 were retrospectively studied. These patients had endophthalmitis at least two months following glaucoma filtering surgery. Bleb-associated endophthalmitis occurred in 2 eyes following filtering surgery with no antifibrotic agent, in 6 eyes following trabeculectomy with 5-FU, and in 7 eyes that underwent trabeculectomy with intraoperative MMC. The mean time from surgery to endophthalmitis following 5-FU was 25.0+/-22.0 months (range 3 to 56 months), and 11.3+/-5.4 months (range 4 to 18 months) following the use of MMC. The estimated cumulative incidences of bleb-associated endophthalmitis in superior blebs at 24 months following surgery were 0.3% for surgeries without antifibrotic agents, 0.8% for trabeculectomies with postoperative 5-FU, and 1.3% for trabeculectomies with intraoperative MMC. No significant differences were demonstrated between the survival distributions of filtering procedures performed with any of the three techniques (p = 0.166, Log-rank test). Most of the cases following 5-FU or MMC appeared within 18 months following trabeculectomy. The visual outcome of most of the eyes was poor. Antifibrotic agents are not associated with a higher risk for late-onset, bleb-associated endophthalmitis. A high rate of alertness is warranted for diagnosis of early signs of infection following glaucoma filtering surgery.

Adult↗
PubMed1999

Experiences of anger in people who have recovered from depression and never-depressed people.

Previous research has linked anger suppression with depression. This study extended prior research by comparing people who had recovered from a major depression (RD) with those who had never been depressed (ND). The RD group significantly exceeded the ND group in the degree to which they reported holding anger in and being afraid to express it. Also, RD participants were more likely to endorse attitudes consistent with silencing the self theory, believing they must hide their feelings to preserve relationships. They were also more likely to have experienced an anger attack. Both silencing the self and a history of anger attacks were significantly correlated with fear of anger expression; future longitudinal or experimental studies are needed to determine whether these variables play a causal role in anger inhibition and in recurrence of depression.

Adaptation, Psychological↗
PubMed1999

Repertoire of human antibodies against the polysaccharide capsule of Streptococcus pneumoniae serotype 6B.

We examined the repertoire of antibodies to Streptococcus pneumoniae 6B capsular polysaccharide induced with the conventional polysaccharide vaccine in adults at the molecular level two ways. In the first, we purified from the sera of seven vaccinees antipneumococcal antibodies and determined their amino acid sequences. Their VH regions are mainly the products of VH3 family genes (candidate genes, 3-23, 3-07, 3-66, and 3-74), but the product of a VH1 family gene (candidate gene, 1-03) is occasionally used. All seven individuals have small amounts of polyclonal kappa+ antibodies (Vkappa1 to Vkappa4 families), although kappa+ antibodies are occasionally dominated by antibodies formed with the product of the A27 Vkappa gene. In contrast, lambda+ anti-6B antibodies are dominated by the antibodies derived from one of 3 very similar Vlambda2 family genes (candidate genes, 2c, 2e, and 2a2) and Clambda1 gene product. The Vlambda2(+) antibodies express the 8.12 idiotype, which is expressed on anti-double-stranded-DNA antibodies. In one case, Vlambda is derived from a rarely expressed Vlambda gene, 10a. In the second approach, we studied a human hybridoma (Dob1) producing anti-6B antibody. Its VH region sequence is closely related to those of the 3-15 VH gene (88% nucleotide homology) and JH4 (92% homology). Its VL region is homologous to the 2a2 Vlambda2 gene (91%) and Jlambda1/Clambda1. Taken together, the V region of human anti-6B antibodies is commonly formed by a VH3 and a Vlambda2 family gene product.

Adult↗
PubMed1999

Tertiary structure of human lambda 6 light chains.

AL amyloidosis is a disease process characterized by the pathologic deposition of monoclonal light chains in tissue. To date, only limited information has been obtained on the molecular features that render such light chains amyloidogenic. Although protein products of the major human V kappa and V lambda gene families have been identified in AL deposits, one particular subgroup--lambda 6--has been found to be preferentially associated with this disease. Notably, the variable region of lambda 6 proteins (V lambda 6) has distinctive primary structural features including the presence in the third framework region (FR3) of two additional amino acid residues that distinguish members of this subgroup from other types of light chains. However, the structural consequences of these alterations have not been elucidated. To determine if lambda 6 proteins possess unique tertiary structural features, as compared to light chains of other V lambda subgroups, we have obtained x-ray diffraction data on crystals prepared from two recombinant V lambda 6 molecules. These components, isolated from a bacterial expression system, were generated from lambda 6-related cDNAs cloned from bone marrow-derived plasma cells from a patient (Wil) who had documented AL amyloidosis and another (Jto) with multiple myeloma and tubular cast nephropathy, but no evident fibrillar deposits. The x-ray crystallographic analyses revealed that the two-residue insertion located between positions 68 and 69 (not between 66 and 67 as previously surmised) extended an existing loop region that effectively increased the surface area adjacent to the first complementarity determining region (CDR1). Further, an unusual interaction between the Arg 25 and Phe 2 residues commonly found in lambda 6 molecules was noted. However, the structures of V lambda 6 Wil and Jto also differed from each other, as evidenced by the presence in the latter of certain ionic and hydrophobic interactions that we posit increased protein stability and thus prevented amyloid formation.

Amino Acid Sequence↗
PubMed1998

Light chain-associated amyloid deposits comprised of a novel kappa constant domain.

Light chain-associated amyloidosis is characterized by the deposition as fibrils of monoclonal light chain-related components consisting predominately of the variable domain (VL) or the VL plus up to approximately 60 residues of the constant domain (CL). Here, we describe a patient (designated BIF) with light chain-associated amyloidosis and kappa Bence Jones proteinuria in whom, notably, >80% of the amyloid deposits were comprised of CL-related material. The extracted amyloid protein consisted of 99 aa residues identical in sequence to the main portion of the Ckappa region (positions 109-207) of the precursor Bence Jones protein. Remarkably, the CLs from both molecules contained a Ser-->Asn substitution at position 177. This heretofore undescribed Ckappa alteration did not result from somatic mutation but rather was germline encoded. When tested in our in vitro fibrillogenic kinetic assay, Bence Jones protein BIF was highly amyloidogenic. Notably, endopeptidase treatment of amyloid fibrils prepared from the native light chain revealed the VL to be markedly susceptible to enzymatic digestion, whereas the CL was protease-resistant. Our findings provide evidence that the fragmented light chains typically present in this disease result from proteolytic degradation and suggest that, in this case, conformational differences in VL/CL packing within the fibrils may account for the unusual composition of the amyloid deposits. Additionally, we posit that the previously unrecognized Asn177 substitution represents yet another Ckappa allotype, provisionally designated Km4.

Aged↗
PubMed1998

Intercellular communication between vascular smooth muscle and endothelial cells mediated by heparin-binding epidermal growth factor-like growth factor and vascular endothelial growth factor.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen and migration factor for vascular smooth muscle cells (SMC), promoted neovascularization in vivo in the rabbit cornea. MRI demonstrated quantitatively the angiogenic effect of HB-EGF when introduced subcutaneously into nude mice. HB-EGF is not directly mitogenic to endothelial cells but it induced the migration of bovine endothelial cells and release of endothelial cell mitogenic activity from bovine vascular SMC. This mitogenic activity was specifically blocked by neutralizing anti-vascular endothelial growth factor (VEGF) antibodies. In contrast, EGF or transforming growth factor-alpha (TGF-alpha) had almost no effect on release of endothelial mitogenicity from SMC. In addition, RT-PCR analysis demonstrated that VEGF165 mRNA levels were increased in vascular SMC 4-10-fold by 0.35-2 nM of HB-EGF, respectively. Our data suggest that HB-EGF, as a mediator of intercellular communication, may play a new important role in supporting wound healing, tumor progression and atherosclerosis by stimulating angiogenesis.

Animals↗
PubMed1998

Prevalence of occupational lung disease in a random sample of former mineworkers, Libode District, Eastern Cape Province, South Africa.

BACKGROUND: Gold mineworkers in South Africa are exposed to high levels of silica dust as a result of which they are at risk of developing silicosis, which is a compensable disease. The incidence of tuberculosis is also high. METHODS: To determine the prevalence of occupational lung disease and the previous compensation history in former migrant mineworkers, a study was undertaken in a random sample of men living in Libode, a rural district of Eastern Cape Province, South Africa. Two hundred thirty-eight ex-mineworkers were examined according to a protocol that included chest radiography and spirometry. Chest radiographs were read into the International Labour Organisation (ILO) classification for pneumoconioses by two readers. RESULTS: The mean age was 52.8 years, and the mean length of service was 12.15 years. The prevalence of pneumoconiosis (> or = ILO 1/0) was 22% and 36% (variation by reader). For both readers, a significant association between length of service and pneumoconiosis and between pneumoconiosis and reduction in FVC and FEV was found. Twenty-four percent of study subjects were eligible for compensation. CONCLUSION: There is a high prevalence of previously undiagnosed, uncompensated pneumoconiosis in the study group. As a result of the failure to diagnose and compensate occupational lung disease, the social and economic burden of such disease is being borne by individuals, households, and the migrant labor-sending communities as a whole.

Adult↗
PubMed1998

Limbal cell autograft transplantation for severe ocular surface disorders.

BACKGROUND: Limbal cell transplantation may improve the visual outcome after chemical trauma and ocular surface diseases. METHODS: Nine eyes of nine consecutive patients (eight males and one female, age 9-60 years), underwent limbal autograft transplantation (LAUT). In five cases LAUT was done for severe chemical burns in the acute stage (group 1). In four patients with old chemical trauma LAUT was performed years after the trauma (group 2). Penetrating keratoplasty (PKP) was carried out within 6 months after LAUT in three patients of group 2. Preoperatively, the visual acuity in all the patients except one was counting fingers. Postoperatively, patients were treated with topical antibiotics, topical corticosteroids and oral steroids. Oral cyclosporin was used after penetrating keratoplasty. RESULTS: No complications were observed during the surgical procedure. Postoperatively, the epithelialization was complete between days 7 and 12. The inflammatory response subsided within 3 months and the stromal neovascularization decreased. Visual acuity improved in all the nine cases, ranging from 6/6 to 6/30. The decreased visual acuity was due to corneal haze, scars and vascularization. Following PKP, the three grafts remained clear with intact epithelium. No complications were observed during the follow-up period from 7 to 60 months. CONCLUSIONS: Limbal cell transplantation is an efficacious procedure for rehabilitation of visual acuity after severe chemical trauma.

Acids↗
PubMed1998

Nerve growth factor is preformed in and activates human peripheral blood eosinophils.

BACKGROUND: Recent studies have shown that nerve growth factor (NGF) is produced by and can act on several immune-inflammatory cells. OBJECTIVES: The objective of this study was to study the effects of NGF on human peripheral blood eosinophils and assess whether these cells produce and store NGF. METHODS: Eosinophils were purified by negative immunoselection (magnetic cell sorting systems, purity 98% to 100%) from 13 subjects (9 to 26 years old) with mild blood eosinophilia, mainly of allergic origin. Eosinophils were incubated with NGF (50 to 1000 ng/mL), and supernatants were collected for measurement of eosinophil peroxidase (EPO, 20 minutes, colorimetric enzymatic assay) and IL-6 (12 hours, ELISA). Eosinophil viability was evaluated by Trypan blue test (days 2, 3, and 4). NGF content in freshly isolated eosinophils, after ultrasound disruption, was determined with a 2-site immunoenzymatic assay. The presence of mRNA for NGF was evaluated by reverse transcription PCR. RESULTS: NGF caused EPO release (highly significant at 1000 ng/mL NGF). IL-6 release from eosinophils was not higher than IL-6 spontaneously released into culture medium alone. NGF did not significantly affect the number of viable eosinophils. NGF was found in the eosinophil sonicates (1.5 to 17.8 pg/mL per 106 cells). Similarly, mRNA for NGF was detected by reverse transcription PCR in the freshly isolated eosinophils. CONCLUSIONS: NGF activates human peripheral blood eosinophils from subjects with mild eosinophilia to selectively release inflammatory mediators. Eosinophils store and produce NGF. Therefore the capability of NGF to induce a secretory response and its production and storage by circulating human eosinophils suggest a possible role for NGF in conditions associated with eosinophilia, including allergic disease.

Adolescent↗
PubMed1998

Priming irrational beliefs in recovered-depressed people.

Major depression has been linked with endorsement of irrational beliefs in cross-sectional research, consistent with the rational emotive behavior therapy (REBT) model. In this study, the authors extended prior research by using multiple measures of irrationality and by comparing never-depressed (ND) controls with people who had recovered from major depression. Contrary to the REBT model, the recovered-depressed (RD) group did not significantly exceed the ND group in irrational beliefs before, during, or after exposure to simulated stressful situations. However, associations between irrationality and negative mood, and to a lesser extent between situation-specific irrationality and personality vulnerabilities, were obtained in the RD group but not in the ND group. These findings are consistent with the possibility that RD persons on average may be especially susceptible to having irrationality primed by negative mood states or by the important setbacks that can lead to such mood states.

Adult↗
PubMed1998

A comparison of the effect of hyaluronic acid versus gentamicin on corneal epithelial healing.

PURPOSE: An animal model study was conducted to compare the efficacy of recurrent topical applications of hyaluronic acid and gentamicin ointment for the treatment of noninfected, mechanical corneal erosions. METHODS: An artificial, controlled wound of identical size and depth was inflicted to the corneas of three groups of rabbit eyes in order to measure their healing rates. One group was treated with hyaluronic acid (10 eyes) while the second group received gentamicin ointment (10 eyes). The third group remained untreated and served as the control (10 eyes). The rate of re-epithelisation was measured at 8-h intervals until complete re-epithelisation was observed. After complete wound closure, the rabbits were killed, and comparative histological examinations were performed. RESULTS: Rabbit eyes treated with hyaluronic acid showed a significantly enhanced rate of epithelial defect closure compared with untreated eyes and a similar rate to that achieved with gentamicin ointment. In the eyes treated with hyaluronic acid a normal, multilayered epithelium was observed 48 h after complete healing, whereas the gentamicin-treated eyes showed an imperfectly layered epithelium, with irregularity of the cuboidal cells. CONCLUSION: While both hyaluronic acid and gentamicin enhance corneal epithelial healing at comparable rates, our study suggests that hyaluronic acid may have a more favourable effect on the structure of the healing epithelium, and can offer an alternative mode of therapy for non-infectious corneal erosions.

Animals↗
PubMed1998

The effect of tear substitute and silicone oil on re-epithelisation of the cornea.

PURPOSE: An animal model study was conducted to compare the effects of recurrent applications of an artificial cellulosic tear substitute and silicone oil on corneal reepithelisation. METHODS: A controlled wound was inflicted to the corneas of two groups of rabbits; one group was treated with tear substitute (5 eyes), while the other group received silicone oil (5 eyes). The left eye served as the control in both groups (10 eyes). The rate of re-epithelisation was measured at intervals of 6 h until complete wound closure was observed. After complete wound closure, the rabbits were killed and histological examinations were performed. RESULTS: The wounds of eyes treated with tear substitute closed at a statistically significant faster rate (at 24, 44, 80 h; p < 0.05) than those treated with silicone oil or the untreated eyes. At 48 h after re-epithelisation, the eyes treated with tear substitute presented a normal epithelium while the untreated and silicone-treated eyes presented an abnormally structured epithelium. CONCLUSION: This study demonstrates a favourable effect of tear substitute on corneal re-epithelisation in an animal model, in terms of both rate of re-epithelisation and histological aspects of the new epithelium.

Animals↗