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Biomedical subjects

A Solomon

Publications and source records attributed to A Solomon.

At least 91 records · Page 5Linked to original sources

Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats.

Postinjury recovery in most tissues requires an effective dialog with macrophages; however, in the mammalian central nervous system, this dialog may be restricted (possibly due to its immune-privileged status), which probably contributes to its regeneration failure. We circumvented this by implanting macrophages, pre-exposed ex vivo to peripheral nerve segments, into transected rat spinal cord. This stimulated tissue repair and partial recovery of motor function, manifested behaviorally by movement of hind limbs, plantar placement of the paws and weight support, and electrophysiologically by cortically evoked hind-limb muscle response. We substantiated these findings immunohistochemically by demonstrating continuity of labeled nerve fibers across the transected site, and by tracing descending fibers distally to it by anterograde labeling. In recovered rats, retransection of the cord above the primary transection site led to loss of recovery, indicating the involvement of long descending spinal tracts. Injection of macrophages into the site of injury is relatively non-invasive and, as the cells are autologous, it may be developed into a clinical therapy.

Animals↗

Differences in kappa to lambda (kappa:lambda) ratios of serum and urinary free light chains.

Free light chains (FLC) are a natural product of B lymphocytes and, as such, represent a quantifiable biomarker of cellular proliferation. Accurate measurement of the concentrations of these components in serum and urine provides a unique means of ascertaining B cell immunoglobulin synthesis during physiologic and, especially, pathologic states, where such information has important diagnostic and therapeutic implications. Previously, use of such quantitative assays has been limited due to the lack of potent serologic reagents specific for these components. We have immunized mice with kappa- and lambda-type monoclonal human light chains (Bence Jones proteins (BJP)) and have obtained monoclonal antibodies (MoAbs) that differentiate between unbound and bound light chains. These highly specific MoAbs were used to measure by ELISA the concentrations of FLC in the serum of 22 normal individuals and in urine from 16 of these subjects. The mean serum kappa and lambda FLC concentrations were found to be 16.6+/-6.1 microg/ml and 33.8+/-14.8 microg/ml, respectively. In contrast, the values for urinary kappa and lambda FLC were 2.96+/-1.84 microg/ml and 1.07+/-0.69 microg/ml, respectively. In each case studied, the serum kappa:lambda ratio was consistently less than that of urine (mean values, serum approximately 1:2; urine approximately 3:1). That the rate of synthesis of lambda-type FLC exceeded that of kappa was evidenced in assays of culture fluid supernatants of unstimulated normal peripheral blood mononuclear cells (PBMC), where the mean kappa:lambda ratio was determined to be 1:1.4. Metabolic studies in which mice were injected with pools of kappa- and lambda-type BJP prepared in ratios of 1:1, 1:2 and 1:4 demonstrated that, regardless of the proportion, kappa FLC were preferentially excreted. Our studies provide the first evidence that lambda FLC are secreted by normal PBMC at a greater rate than are kappa FLC, as evidenced in biosynthetic studies and by measurement of their serum concentrations. Further, we posit that quaternary structural differences between the two light-chain isotypes may account for the predominance of kappa versus lambda components in urine.

Adult↗

Deep stromal inflammation--a possible new ocular manifestation of Crohn's disease.

Crohn's disease, an inflammatory bowel disease, is infrequently associated with epithelial and subepithelial corneal inflammation. However, deep stromal inflammation has not been described previously in association with Crohn's disease. We report on a 52-year-old male who suffered from anterior uveitis and deep stromal inflammation. Complete ocular and systemic workup revealed an active asymptomatic Crohn's colitis; no other possible cause for the ocular inflammation was found. We conclude that deep stromal inflammation, in addition to the previously reported corneal epithelial inflammation, may be associated with Crohn's disease.

Colitis↗

The effect of a new tear substitute containing glycerol and hyaluronate on keratoconjunctivitis sicca.

The purpose of this study was to evaluate the efficacy of LO2A, a newly developed tear substitute containing glycerine and sodium hyaluronate, in the treatment of dry eyes. Twenty-five informed consent patients suffering from keratoconjunctivitis sicca were included. Patients were treated for one week with LO2A in one eye, and with their current tear substitute in the other eye. Rose bengal staining was evaluated on a scale of 0 to 3. Patient satisfaction was graded on a scale of 1 to 5. The average satisfaction score for LO2A was significantly higher compared to the control preparations at 1 week (p=0.0003) and at 2 weeks (p=0.0232). A highly significant reduction in rose bengal staining was demonstrated following 1 week of treatment with LO2A (p<0.0001). The LO2A treated eyes had significantly less staining than control eyes at 1 week (p=0.021) and at 2 weeks (p=0.023). An inverse correlation was found between patient grading and the rose bengal scoring (spearman rank coefficient = -0.49, p<0.001). LO2A showed a beneficiary effect on dry eye patient satisfaction and on rose bengal test, as compared to other tear substitute preparations currently used by these patients.

Drug Evaluation↗

MIB-1 and PC-10 immunostaining for the assessment of proliferative activity in primary acquired melanosis without and with atypia.

AIMS: To compare the proliferative activity of intraepithelial melanocytes in primary acquired melanosis (PAM) without atypia and PAM with atypia by immunohistochemical staining for the Ki-67 antigen and the proliferating cell nuclear antigen (PCNA). METHODS: Formalin fixed, paraffin embedded sections from 35 archival specimens of PAM without atypia (n = 19) and with atypia (n = 16) were studied by immunostaining with MIB-1 and PC-10 monoclonal antibodies that react with the Ki-67 antigen and PCNA respectively. The results were calculated as the mean number of positive cells per eyepiece grid. All specimens were evaluated by two masked observers, and the interobserver reproducibility was assessed. RESULTS: The means of the positive cell count in PAM with atypia were significantly higher compared with PAM without atypia for both observers, in both the PC-10 and the MIB-1 stained sections. In a linear least square model that estimated the interobserver and between group variation, the difference of MIB-1 and PC-10 positive cell count between PAM without and with atypia remained highly significant. The difference between the observers was not significant. CONCLUSIONS: Immunostaining with MIB-1 and PC-10 demonstrated that PAM with atypia has higher proliferative activity than PAM without atypia. This method was found to be reproducible between different observers.

Antigens, Nuclear↗

Common bile duct stenting for choledocholithiasis: a district general hospital experience.

The favoured treatment of common bile duct stones is endoscopic sphincterotomy and stone extraction. The management of those cases where duct clearance is not possible is controversial. At our institution it has been policy to insert an endoluminal stent. We report a retrospective review of the outcome of patients stented for common bile duct stones. The study population was 14 men and 22 women, with a median age of 73 years (range 23-89 years). Treatment-related morbidity was seen in nine patients (25%), comprising cholangitis (5), pancreatitis (3), and cholecystitis (1). Three of these patients died; all were over the age of 75 years and had been stented on a long-term basis. These data suggest that endobiliary stents can be employed with an acceptable complication rate. We suggest that patients under the age of 75 years be stented only as a temporising measure, but that patients over 75 years or those unfit on physiological grounds can be stented on a long-term basis as definitive treatment.

Adult↗

The open-artery hypothesis.

Early reperfusion of an infarct-related coronary artery results in myocardial salvage, with subsequent improvement in left ventricular function and survival. However, late reperfusion, which occurs at a time when myocardial salvage is no longer possible, still exerts a favorable impact on left ventricular function and survival. This concept is known as the open-artery hypothesis. Possible mechanisms for this benefit include improved infarct healing, limitation of ventricular remodeling, decreased ventricular arrhythmias, and reperfusion of hibernating myocardium. Although an open infarct-related coronary artery is crucial, it has not been proven that opening an occluded coronary artery using angioplasty is beneficial. A large randomized clinical trial is clearly needed.

Angioplasty, Balloon, Coronary↗

Desiccation tolerance of Muellerius cf. capillaris (Nematoda: Protostrongylidae) first-stage larvae.

Muellerius cf. capillaris is the most common lung worm of wild Nubian ibex (Capra ibex nubiana) in the northern Negev desert, Israel. The capacity of the free-living stages (L1) of the parasite to survive extreme desiccation was tested under 2 different dehydration regimes at 23 C: rapid dehydration through direct exposure to 0% relative humidity (RH), and a slow dehydration regime of preconditioning at 33% RH for 7 days prior to exposure to 0% RH for a further 21 days. In direct exposures to 0% and 33% RH, by day 11 survival rates of L1 were significantly higher than when stored in water and in 97% RH (P < 0.05). The slow dehydration regime enhanced the survival of L1 up to 10-fold by day 28 as compared with direct exposure to 0% RH. The same mean numbers of larvae were recovered from the land snail Theba pisana infected with L1 exposed for 21 days at 33% RH and from T. pisana infected with nondesiccated L1 (P > 0.1). L1 surviving after 21 days of desiccation at 0% RH were, on the other hand, less infective to T. pisana. The percentage of such postdesiccated L1 reaching infective stage (L3) was, however, the same as that of the control group. The ability of M. cf. capillaris L1 to survive anhydrobiosis and retain infectivity to land snails after extreme desiccation enables their coexistence with the Nubian ibex in desert habitat.

Animals↗

Effect of corticosteroids on healing of the corneal endothelium in cats.

BACKGROUND: Anterior segment surgery is frequently complicated by damage to the corneal endothelium. We examined the effects of corticosteroids, which are widely used for the suppression of postoperative inflammation, on the process of endothelial cell regeneration. METHODS: The effect of corticosteroids on healing of the corneal endothelium was examined in 10 domestic cats. In both eyes a circular area, 8 mm in diameter, was scraped off at the center of the corneal endothelium without damaging Descemet's membrane. Immediately after scraping, as well as 2 and 5 days later, each animal received a unilateral retrobulbar injection of betamethasone sodium phosphate (2 mg). The other eye served as a control and received a retrobulbar injection of the vehicle only. RESULTS: Evaluation of the corneal endothelium 2, 5 and 7 days after the trauma revealed that relative to the control contralateral eyes, the corticosteroid-treated eyes exhibited a higher mean coefficient of variation of the corneal endothelium cell area, fewer hexagonal cells, a larger number of polygonal cells with 3, 4 7 and 8 cellular facets, thinner corneas and less inflammation. CONCLUSIONS: These findings suggest that corticosteroids unfavorably affect the regeneration of corneal endothelial cells after injury. As corticosteroids appear to have both positive and adverse effects on corneal function after trauma, they should be used with caution.

Animals↗

Migratory behaviour and desiccation tolerance of protostrongylid nematode first-stage larvae.

Migration of first-stage larvae (L1) from faeces to soil is a crucial stage in the life-history of protostrongylids transmitted via land snails. Migration of Muellerius cf. capillaris and a Cystocaulus sp. L1 from fresh Nubian ibex (Capra ibex nubiana) faeces (48-50% water content, W.C.) to substrate soils (at 100% r.h., 26 degrees C) was measured experimentally using dry (3 +/- 1% W.C.), wet (31 +/- 0.43% W.C.) and flooded (48.4 +/- 2.45% W.C.) soils. The highest migration rates (90.4 +/- 1.6% migration) in both species occurred on flooded soils when the faecal pellet W.C. reached 90%. The next highest migration rates (43.2 +/- 3.6% migration, at 60% faecal W.C.) were on the wet soils and no migration occurred on dry soil or dry-substrate papers. Migration rates did not differ significantly (P > 0.05) between species. Active Theba pisana were not infected by M. cf. capillaris L1 on dry infested soils, but were infected following rehydration of the same soils. By day 10, L1 of M. cf. capillaris demonstrated lower survival rates in water and in 97% and 76% r.h. (74.5%, 15.2% and 1.9%, respectively) than the Cystocaulus sp. (97.5%, 43.8%, 43.3%) and Protostrongylus sp. (97.9%, 43.2%, 23.8%, P < 0.05). All three nematodes had a remarkably high survival rate (> 99% overall survival, by day 10) when exposed directly to 0% r.h. at 23 degrees C. Results demonstrate the ability of L1 to survive extreme desiccation through anhydrobiosis. Migration of L1 from faeces to soil can take place only during rains which coincide with peak activity of land snails in desert habitat.

Animals↗

Temperature-controlled CO2 laser tissue welding of ocular tissues.

Lasers can be used for binding tissues by welding, but the clinical application of this method has been limited by the difficulties in defining and maintaining the optimal conditions. Fiberoptic radiometry allows accurate remote temperature measurements for control of laser tissue welding. We evaluated the use of a temperature-controlled tissue welding system to close corneal and corneoscleral wounds. Eighty ex vivo bovine eyes were used for the determination of welding parameters optimal for corneal wound closure. A 4 mm central corneal cut was closed with use of a CO2 laser (600 mw, 0.9 mm spot size), with tissue temperatures ranging from 45-70 degrees C and welding time ranging from 1-30 seconds. Wound strength was measured as burst pressure of the sealed wound. The welding parameters found to cause the strongest wound binding were used to weld a limbal incision of 4 mm in 10 adult albino rabbits. The fellow eye of each animal was used as a control, and the same wound was closed with one 10/0 mersilen suture. Two animals were killed immediately after the procedure, and the eyes were sent for histologic examination. Eight rabbits were followed for 1 month. Clinical examination and refraction were done 1 day, 1 week, 2 weeks, and 1 month after the procedure. Corneal topographic evaluations were done 1 week after the procedure. After 1 month the animals were killed and the eyes were examined histologically. The optimal results of wound binding by laser welding in the enucleated bovine eyes were achieved with 55-60 degrees C and at a welding time of 12-20 seconds. At these parameters the burst pressure of corneal wounds was 70 mm Hg. All laser-welded limbal wounds in the rabbits were tightly closed at the end of procedure and during the follow-up period. The refractive results after laser welding were equal to those of the controlled suture-closed wound. Laser tissue welding combined with tissue temperature monitoring can be used to close corneal wounds.

Animals↗

Identification and characterization of a human Vlambda5 (T1) germline gene that encodes structurally unique lambda light chains.

The human germline Vlambda repertoire consists of about 30 functional genes that have been classified into 10 families on the basis of homologies in nucleotide sequences that encode approximately the first 96 to 104 residues of lambda light chains. One family, termed Vlambda5, is of special interest because the lambda light chain products of these genes have unique structural features. We have now isolated from genomic DNA one member of this family, designated IGLV5-1, using as a molecular probe a partial Vlambda5-germline-gene fragment generated by polymerase chain reaction. IGLV5-1 contains all the requisite elements of a potentially functional gene, including a Vlambda exon with an open reading frame specifying 104 residues. A Vlambda5-related cDNA (ZW) was also cloned from a bone marrow-derived plasma-cell population obtained from a patient with light-chain-associated (AL) amyloidosis. Comparison of the predicted protein sequences encoded by the IGLV5-1-germline gene, cDNA ZW, and three other reported Vlambda5-related cDNAs with those of the deduced or expressed products of the other nine known human Vlambda-gene families revealed that Vlambda5 proteins contain distinctive primary structural features. These include the presence within the second complementarity determining region (CDR2) and the third framework region (FR3) of 11 and 34 amino acids, respectively, rather than the 7 and 32 that occur in the most commonly expressed Vlambda1-, Vlambda2- and Vlambda3-type light chains. Although certain of the Vlambda-gene families encode either an elongated CDR2 or FR3, Vlambda5 proteins are remarkable in that they have additional residues in both regions of the molecule. In this respect, these polypeptides are most similar to surrogate light-chain-associated human and mouse VpreB components that also have these unusual primary structural features. Further, the four additional CDR2 residues and the two-residue FR3 insertion have been found among lambda-type light chains of certain non-mammalian species. The evolutionarily conserved nature of human Vlambda5-related genes and, in particular, the presumably novel tertiary structural effects induced by the unique features of the lambda light chains encoded by these elements suggest that the Vlambda5-gene family has biological and functional importance.

Amino Acid Sequence↗

Variable domain structure of kappaIV human light chain Len: high homology to the murine light chain McPC603.

Antibody light chains of the kappa subgroup are the predominant light chain component in human immune responses and are used almost exclusively in the antibody repertoire of mice. Human kappa light chains comprise four subgroups. To date, all crystallographic studies of human kappa light chains were carried out on proteins of the kappaI subgroup. The light chain produced by multiple myeloma patient Len. was of the kappaIV subgroup, it differed by only one residue from the germ-line gene encoded protein. The variable domain fragment of the light chain was crystallized from ammonium sulfate in space group C222(1). The crystal structure was determined by molecular replacement and refined at 1.95 A resolution to an R-factor of 0.15. Protein Len has six additional residues in its CDR1 segment compared to the kappaI proteins previously characterized. The kappaIV variable domain, Len, differs in only 23 of 113 residues from murine kappa light chain McPC603. The RMS deviation upon superimposing their alpha-carbons was 0.69 A. The CDR1 segment of the human and murine variable domains have the same length and conformation although their amino acid sequences differ in 5 out of 17 residues. Structural features were identified that could account for the significantly higher stability of the human kappaIV protein relative to its murine counterpart. This human kappaIV light chain structure is the closest human homolog to a murine light chain and can be expected to facilitate detailed structural comparisons necessary for effective humanization of murine antibodies.

Amino Acid Sequence↗

Microbial findings in suture erosion after penetrating keratoplasty.

PURPOSE: The purpose of the study was to evaluate the presence of microorganisms in eroded (broken or loose) sutures post-penetrating keratoplasty (PKP). METHODS: Fifty-five consecutive episodes of eroded 10-0 nylon sutures post-PKP in 35 eyes were evaluated. Eroded sutures were removed and, along with a swab from the conjunctiva, studied for aerobic and anaerobic bacteria. Preoperative diagnosis, elapsed time since surgery, presence of symptoms, suture location, infiltration, vascularization, and mucous at the suture site were recorded. Student's t test was used for statistical analysis. RESULTS: The average time from PKP to suture removal was 31.6 months. Eyes treated with topical steroids presented earlier suture erosions (P = 0.05). Of the 55 sutures, 34 were sterile, and in 21, both Staphylococcus epidermidis and diphtheroids (mixed flora) were cultured. Of the 55 conjunctivas, 32 were sterile, 22 showed mixed flora, and 1 had Pseudomonas. Sutures eroded for more than 24 hours had more positive cultures than those eroded for 24 hours or less (P = 0.043). Sutures located superiorly had fewer positive cultures than did those in the palpebral fissure area (P = 0.044). Eyes with repeated suture erosions had more culture-positive sutures (P = 0.017) and conjuctivas (P = 0.014) at the first erosion in comparison with the second erosion. Infiltration, vascularization, or muscus at the suture site did not correlate with positive cultures. CONCLUSIONS: Bacteria are encountered at the site of eroded sutures. Patients with PKP should report symptoms immediately, and eroded sutures should be removed as early as possible.

Adolescent↗

Biology and therapy of immunoglobulin deposition diseases.

All forms of MIDD represent pathologic deposition of immunoglobulin as amorphous casts, crystals, congophilic fibrils (in AL amyloid), or punctate noncongophilic deposits (in LCDD/HCDD/LHCDD). Diagnosis is based on identification and immunohistochemical characterization of deposits and Congo red staining. Current information including development of novel in vitro and in vivo models suggests a contributory role of both protein and host factors in the pathogenesis of these disorders. In particular, primary structural features of the VL portions of the light chain molecule may affect not only the extent but also the morphologic type of protein deposits. Thus, certain types of light chains may be particularly pathogenic, although the nature or extent of proteolysis/processing involved in the pathogenesis of these deposits is yet unclear. Recent data also point to the importance of accessory molecules, cytokines, and host factors in this process. Newer therapeutic approaches using high-dose therapy with cytotoxic agents or dexamethasone appear promising, although these data need to be confirmed in a larger number of patients. The serendipitous discovery of I-DOX as an agent capable of promoting amyloid resorption provides another novel approach in patients with AL amyloidosis. Continued research on the mechanisms of deposition and resorption of these immunoglobulin deposits should provide important information that can be used to design strategies for more effective therapy and, ultimately, prevention of MIDD.

Amyloidosis↗

A patch in the pectoral position lowers defibrillation threshold.

Implantable pacemaker cardioverter defibrillators are now available with biphasic waveforms, which have been shown to markedly improve defibrillation thresholds (DFTs). However, in a number of patients the DFT remains high. Also, DFT may increase after implantation, especially if antiarrhythmic drugs are added. We report on the use of a subcutaneous patch in the pectoral position in 15 patients receiving a transvenous defibrillator as a method of easily reducing the DFT. A 660-mm2 patch electrode was placed beneath the generator in a pocket created on the pectoral fascia. The energy required for defibrillation was lowered by 56% on average, and the system impedance was lowered by a mean of 25%. This maneuver allowed all patients to undergo a successful implant with adequate safety margin.

Defibrillators, Implantable↗

Thirty years of penetrating keratoplasty in Israel.

We studied the indications for keratoplasty and their changes during 30 years in Israel by retrospective evaluation of pathologic records of 1,018 corneal buttons (from 1961 to 1990). The population included 634 (62.3%) male patients and 384 (37.7%) female patients. Keratoconus (n = 222, 21.8%) was the most common indication, followed by corneal graft failure (n = 113, 11.1%), herpetic infections (n = 95, 9.3%), ocular trauma (n = 87, 8.5%), scarring (n = 74, 7.3%), pseudophakic bullous keratopathy (n = 72, 7.1%), nonherpetic infections (n = 71, 7.0%), and other indications. Whereas ocular infections were the most common indications for keratoplasty before 1970, keratoconus has been the most common indication since 1970. Pseudophakic bullous keratopathy became the second most common indication (13.8%) between the years 1981 and 1990. The number of keratoplasties increased in Israel during the past three decades, and the low percentage of pseudophakic bullous keratopathy is related to the types of intraocular lenses that we implanted in the late 1970s and the early 1980s.

Corneal Diseases↗