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Biomedical subjects

R London

Publications and source records attributed to R London.

At least 37 records · Page 2Linked to original sources

B cell differentiation factor-induced B cell maturation: regulation via reduction in cAMP.

We have previously described a novel human B cell differentiation factor (BCDF), 446-BCDF, that is distinct biochemically and functionally from other cytokines. Since signal transduction pathways involved in human B cell differentiation have been incompletely studied and are poorly understood, we assessed the effects of 446-BCDF on various intracellular second messenger systems. After exposure of B cells to 446-BCDF, intracellular cAMP concentration started to decrease at 5 min and was significantly lower at 30 min and reached the lowest level at 4 hr. In most cases, cAMP concentrations returned toward baseline by 24 hr. A cAMP analog (dibutyryl cAMP), a stimulator of adenyl cyclase (forskolin), and phosphodiesterase inhibitors (aminophylline and IBMX) which inhibited the 446-BCDF-induced decrease in intracellular cAMP, inhibited 446-BCDF-induced B cell differentiation, suggesting that the fall in intracellular cAMP was a critical event in this process. To understand the mechanism involved in the reduction of cAMP, B cells were treated with pertussis toxin (PTX), a Gi protein inhibitor. Pertussis toxin blocked 446-BCDF-induced B cell differentiation as well, suggesting that 446-BCDF may function by stimulation of a Gi-linked receptor resulting in the inhibition of adenylate cyclase with a consequent reduction in cAMP. Other cytokines known to promote Ig secretion (IL2 and IL6) also caused a reduction in cAMP, suggesting that this pathway may be generally important in B cell differentiation. Taken together, these data suggest that at least one pathway of terminal maturation in B cells may involve the reduction of intracellular cAMP.

Adenylate Cyclase Toxin↗

The economic value of contraception: a comparison of 15 methods.

OBJECTIVES: The purpose of the study was to determine the clinical and economic impact of alternative contraceptive methods. METHODS: Direct medical costs (method use, side effects, and unintended pregnancies) associated with 15 contraceptive methods were modeled from the perspectives of a private payer and a publicly funded program. Cost data were drawn from a national claims database and MediCal. The main outcome measures included 1-year and 5-year costs and number of pregnancies avoided compared with use of no contraceptive method. RESULTS: All 15 contraceptives were more effective and less costly than no method. Over 5 years, the copper-T IUD, vasectomy, the contraceptive implant, and the injectable contraceptive were the most cost-effective, saving $14,122, $13,899, $13,813, and $13,373, respectively, and preventing approximately the same number of pregnancies (4.2) per person. Because of their high failure rates, barrier methods, spermicides, withdrawal, and periodic abstinence were costly but still saved from $8933 to $12,239 over 5 years. Oral contraceptives fell between these groups, costing $1784 over 5 years, saving $12,879, and preventing 4.1 pregnancies. CONCLUSIONS: Contraceptives save health care resources by preventing unintended pregnancies. Up-front acquisition costs are inaccurate predictors of the total economic costs of competing contraceptive methods.

Contraception↗

The importance of periodontal pathogens in guided periodontal tissue regeneration and guided bone regeneration.

Although guided tissue regeneration (GTR) procedures in periodontitis lesions and around endosseous dental implants represent exciting new therapeutic modalities in periodontics, these treatments can fail because of shortcomings in surgical techniques, restriction in the size and shape of the defect, anatomic features interfering with surgery, or infectious complications. Our studies show that optimal tissue regeneration cannot be expected for a nonbioabsorbable barrier membrane placed in a site infected by periodontopathic microorganisms. Our data also indicate that treatment failure is most frequent in patients who harbor high levels of periodontal pathogens and show evidence of severe periodontitis in numerous teeth. To decrease the risk of infection and to ensure proper healing, periodontal therapy should precede insertion of the barrier membrane for GTR. Recently, we have studied the effect of the pathogens on periodontal GTR and guided bone regeneration around dental implants and the results are reviewed in this article.

Biofilms↗

Cytokine production by primary bone marrow megakaryocytes.

Primary human bone marrow megakaryocytes were studied for their ability to express and release cytokines potentially relevant to their proliferation and/or differentiation. The purity of the bone marrow megakaryocytes was assessed by morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern blot analysis. At the protein level, megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture supernatants. Transforming growth factor-beta was also able to stimulate IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol-12-myristate-13-acetate (PMA). The secreted cytokines acted additively to maintain and increase the number of colony-forming unit-megakaryocytes colonies (approximately 35%). These studies demonstrate the production of multiple cytokines by isolated human bone marrow megakaryocytes constitutively or stimulated in vitro. The capacity of human megakaryocytes to synthesize several cytokines known to modulate hematopoietic cells supports the concept that there may be an autocrine mechanism operative in the regulation of megakaryocytopoiesis.

Bone Marrow↗

Identification and characterization of a novel tyrosine kinase from megakaryocytes.

Protein-tyrosine kinases play pivotal roles in cell signal transduction. We have isolated a cDNA clone encoding a novel human intracytoplasmic tyrosine kinase, termed matk (megakaryocyte-associated tyrosine kinase). Expression of matk mRNA was predominantly found in cells of megakaryocytic lineage. The matk cDNA clone encodes a polypeptide of 527 amino acids and has closest sequence similarity to the csk tyrosine kinase. Sequence comparisons also indicate that matk contains src homology region 2 and 3 domains but lacks the NH2-terminal myristylation signal, the negative regulatory tyrosine (Tyr-527), and the autophosphorylation site (Tyr-416) corresponding to those found in src. Antibodies raised against the NH2 terminus of matk immunoprecipitated a 60-kDa protein from the CMK human megakaryocyte cell line. Expression of matk mRNA was up-regulated in megakaryocytic cells induced to differentiate by the phorbol ester. Based on its restriction in expression and its modulation during in vitro differentiation, it is likely that matk participates in signal transduction during megakaryocytopoiesis.

Base Sequence↗

Soft opaque contact lenses in binocular vision problems.

Soft opaque contact lenses may be useful in certain recalcitrant vision problems. When the full central area is opaque, contact lenses eliminate the visual image, provide acceptable cosmesis, and may be useful in cases of intractable diplopia as well as in the treatment of amblyopia. Artificial iris contact lenses eliminate para-axial rays in monocular diplopia, aniridia, and albinism.

Albinism, Oculocutaneous↗

Differences in pattern visual evoked potential (PVEP) between hemodialysis and peritoneal dialysis patients.

The visual evoked potential was recorded in peritoneal and hemodialysis patients as compared to normal controls. By using the appropriate visual stimulus we were able to disclose specific VEP abnormalities for each of the two dialysis groups. The dissociation found between the latency of N70 and P100 in peritoneal dialysis patients suggests a possible postsynaptic visual abnormality not described previously. The correlation between the high serum aluminum and the P100 latency of peritoneal dialysis patients requires further investigation.

Adult↗

Anisocoria. Variation and clinical observation with different conditions of illumination and accommodation.

Variations in anisocoria in light and dark conditions are used to help diagnose normal and pathologic conditions; however, there have been few observations of anisocoria in different lighting and accommodative conditions. The authors measured pupil size photographically in a group of normal subjects examined in six conditions that were controlled for illumination and accommodation. Greater variation and average extent of anisocoria were found in conditions that resulted in larger pupil size. A subset of subjects repeated several sessions. For this group, the average value of anisocoria and variability tended to be greater in dark conditions. These results show that the observation of anisocoria varies under different conditions, and they suggest careful consideration of conditions used clinically to assess pupil equality. Our analysis shows that for a given observation threshold, conditions that produce even modest changes in variability can cause dramatic changes in the probability of observing anisocoria.

Accommodation, Ocular↗

Changes in refractive error for exotropes treated with overminus lenses.

The refractive changes of pediatric patients who were prescribed overminus lenses for exotropia were evaluated. Overminus lenses means additional minus power over the lenses required to correct the refractive error at distance. Forty exotropic patients, ages 1 to 15 years, were prescribed overminus lenses (-0.50 D to -3.75 D) for a period of 9 to 86 months. A small but significant correlation was found between the initial refractive error and the mean annual change toward myopia. Other factors such as age when treatment was given, duration of therapy, amount of overminus, and the amount of the exodeviation had little effect on the rate of myopic change. The mean annual changes in refractive error for hyperopes (-0.13 +/- 0.44 D, N = 15), emmetropes (-0.26 +/- 0.37 D, N = 17), and myopes (-0.75 +/- 0.77 D, N = 18) were similar to values reported in the literature for nonexotropic children.

Adolescent↗

Analysis of binocular visual function using tests made under binocular conditions.

Accommodation and vergence have a complex relation which occasionally breaks down, resulting in a loss of visual efficiency along with symptoms of discomfort associated with use of the eyes. Studies of accommodation/vergence interactions and tonic vergence disorders indicate that, using classical analysis techniques, separate methods are frequently necessary to determine whether existing binocular deficiencies are causing reported symptoms. The problem with current systems of binocular visual function analysis is that the vergence error which exists under binocular conditions is often not the same as that which is measured under monocular conditions. A rationale for, and technique of, analyzing binocular function using results of tests made under binocular conditions is described. This analysis incorporates the concepts of CA/C, proximal vergence (PV), and fixation disparity along with several accommodative measures (facility, lag, sustaining ability, and accuracy). By identifying relevant binocular components and the interrelations, the clinician should be better able to assess the contribution of each and examine which may be modified most easily by vision therapy, lenses, and/or prism intervention.

Accommodation, Ocular↗

Sensory fusion disruption syndrome.

Unlike the typical manifestation of acquired strabismus, patients with sensory fusion disruption syndrome are unable to fuse targets even when bifoveally aligned under ideal clinical conditions. This condition usually follows trauma and a period of coma. These patients suffer from chronic diplopia which is not relieved by optical or surgical means. Recognition of this entity may result in more effectual management. As a phenomenon, it serves as a potential clue to physiological composition of binocularity.

Adolescent↗

Monovision correction for diplopia.

Acquired, incomitant strabismus frequently results in diplopia. Affected patients complain of chronic annoyance and frustration with the false image. Therapy has usually been aimed at either re-establishing binocularity by using prisms or vision training, or by eliminating one image through occlusion. An alternative approach is to allow each eye its own "domain," one eye corrected for distance vision and the other for near vision. This alternative may eliminate the competitive, unfusible images and yet maintain visual function in each eye.

Adult↗

Interexaminer reliability of the optic cup to disc ratio assessment.

Previous controlled reliability studies of cup to disc (C/D) ratio estimations may have been biased by lack of criteria for cup determination, small sample size; and/or large interval grouping of collected data. In our study four examiners independently estimated the C/D ratios of 40 patients by direct ophthalmoscopy using a contour criterion for cup determination. Results indicated that 75% of the estimate pairs differed by 0.10 or less. Fewer than 14% of the estimate pairs differed by 0.2 or greater. The results of the study suggest that when examiners use a specified criterion of contour cupping, interexaminer assessment of the C/D ratio estimation is clinically and statistically reliable.

Adolescent↗

Urinary tract involvement in EEC syndrome.

A patient with fully expressed, sporadic ectrodactyly, ectodermal dysplasia, and cleft lip and/or palate (EEC) syndrome with renal involvement is presented; descriptions of four similar patients were found in the literature. Based on these patients, we suggest that the renal involvement is a form of dysplasia secondary to fetal urinary tract obstruction. We emphasize the importance of searching for a urinary tract anomaly in patients with this uncommon syndrome.

Abnormalities, Multiple↗

Pseudomembranous colitis following low dose trimethoprim-sulfamethoxazole.

A 94-year-old man had pseudomembranous colitis while taking low dose trimethoprim-sulfamethoxazole for recurrent urinary tract infection. The suppressive effect of low dose trimethoprim-sulfamethoxazole on normal colonic flora appeared to be a factor in the development of pseudomembranous colitis in this patient.

Aged↗

Soft bifocal contact lenses for patients with nearpoint asthenopia.

Bifocal contact lenses have generally been considered solely for the presbyopic population. However, pre-presbyopic individuals with accommodative or vergence disorders who respond favorably to plus lenses at near may be good candidates for bifocal contact lenses. A group of ten non-presbyopic patients who manifest accommodative dysfunctions or near point esophoria were fit with the Ciba BI-SOFT contact lenses. Nearpoint accommodative and vergence findings were evaluated through both near point plus spectacle lenses and the bifocal soft lenses. Results indicate that the BI-SOFT bifocal contact lens was effective in changing the near point visual posture. However, poor distance vision acuity due to ghost images reduced the subjective success rate of the BI-SOFT lens on this non-presbyopic population.

Adult↗