PubMed Health⌕ Search

Biomedical subjects

N Wolfson

Publications and source records attributed to N Wolfson.

At least 19 recordsLinked to original sources
PubMed1998

2-Deoxy derivative is a partial agonist of the intracellular messenger inositol 3,4,5,6-tetrakisphosphate in the epithelial cell line T84.

We have synthesized the first deoxy analogues of myo-inositol 3,4,5, 6-tetrakisphosphate (1) [Ins(3,4,5,6)P4], rac-2-deoxy-myo-inositol 3, 4,5,6-tetrakisphosphate (rac-2), 2-deoxy-myo-inositol 1,4,5, 6-tetrakisphosphate (ent-2), and rac-1-deoxy-myo-inositol 3,4,5, 6-tetrakisphosphate (rac-3). In order to evaluate the binding properties of the three derivatives to the yet unidentified intracellular binding sites for Ins(3,4,5,6)P4, the analogues were converted to membrane-permeant derivatives. Starting with common inositol precursors, various forms of Barton-McCombie deoxygenation and classical protection/deprotection procedures yielded the desired precursors rac-1-O-butyryl-2-deoxy-myo-inositol (rac-12), ent-3-O-butyryl-2-deoxy-myo-inositol (ent-12), and rac-2-O-butyryl-1-deoxy-myo-inositol (rac-19), respectively. Phosphorylation and subsequent deprotection yielded rac-2, ent-2, and rac-3. Alternatively, phosphorylation followed by alkylation with acetoxymethyl bromide gave the membrane-permeant derivatives 1-O-butyryl-2-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (rac-5), 3-O-butyryl-2-deoxy-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (ent-5), and 2-O-butyryl-1-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (rac-6), respectively. We examined the potency of the membrane-permeant deoxy derivatives in inhibition of calcium-mediated chloride secretion (CaMCS) in intact T84 cells. Compared to the 1,2-di-O-butyryl-myo-inositol 3,4,5, 6-tetrakisphosphate octakis(acetoxymethyl) ester (4), the membrane-permeant derivative of Ins(3,4,5,6)P4 (1), the 2-deoxy derivative (rac-5) exhibited a slightly weaker inhibitory effect, while the enantiomerically pure 2-deoxy-Ins(1,4,5,6)P4 (ent-5) and the 1-deoxy derivative (rac-6) were inactive. As expected, the effect was stereoselective. Thus, the 1-hydroxyl group is apparently essential for binding and the inhibitory effect of Ins(3,4,5,6)P4 on chloride secretion, whereas the 2-hydroxyl group plays a less important role.

Calcium↗
PubMed1998

Retrospective analysis of alternate-day prednisone maintenance therapy for Crohn's disease.

We reviewed the medical records of 98 children with Crohn's disease followed at Children's Hospital of Pittsburgh from 1983 to 1993 to evaluate the merits of alternate-day prednisone (AD) maintenance therapy once initial remission was achieved. Of the 98 children, 35 had adequate data recorded for eligibility to the study. Of these, 11 were in the AD group and 24 were in a group whose maintenance regimen did not include prednisone (NO). The dependent variables were frequency of flares and linear growth over time. AD therapy reduced mean symptomatic flares (0.23 +/- 0.1 vs 0.69 +/- 0.14 flares/patient/year; p = 0.04) over a 2-year follow-up period but did not delay significantly the onset of a flare after remission was achieved (16.5 +/- 3.4, vs 13.4 +/- 1.8 months; p = 0.4). Site of disease involvement had no impact on frequency of flares. Fewer patients in the AD group experienced flares, but this finding did not achieve statistical significance (4/11, 36%, vs 17/24, 71%; p = 0.07). Linear growth, measured in height percentile and growth velocity (cm/year), was not significantly reduced by the second year of either therapy. This small retrospective study suggests that AD prednisone therapy may be effective in reducing symptomatic flares in Crohn's patients without a resultant inhibition of linear growth.

Adolescent↗
PubMed1997

D-myo-Inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways.

Several inositol-containing compounds play key roles in receptor-mediated cell signaling events. Here, we describe a function for a specific inositol polyphosphate, D-myo-inositol 1,4,5,6-tetrakisphosphate [Ins(1,4,5,6)P4], that is produced acutely in response to a receptor-independent process. Thus, infection of intestinal epithelial cells with the enteric pathogen Salmonella, but not with other invasive bacteria, induced a multifold increase in Ins(1,4,5,6)P4 levels. To define a specific function of Ins(1,4,5,6)P4, a membrane-permeant, hydrolyzable ester was used to deliver it to the intracellular compartment, where it antagonized epidermal growth factor (EGF)-induced inhibition of calcium-mediated chloride (Cl-) secretion (CaMCS) in intestinal epithelia. This EGF function is likely mediated through a phosphoinositide 3-kinase (PtdIns3K)-dependent mechanism because the EGF effects are abolished by wortmannin, and three different membrane-permeant esters of the PtdIns3K product phosphatidylinositol 3,4,5-trisphosphate mimicked the EGF effect on CaMCS. We further demonstrate that Ins(1,4,5,6)P4 antagonized EGF signaling downstream of PtdIns3K because Ins(1,4,5, 6)P4 interfered with the PtdInsP3 effect on CaMCS without affecting PtdIns3K activity. Thus, elevation of Ins(1,4,5,6)P4 in Salmonella-infected epithelia may promote Cl- flux by antagonizing EGF inhibition mediated through PtdIns3K and PtdInsP3.

Epidermal Growth Factor↗
PubMed1995

Moore hemiarthroplasty functioning for 33 years: a case report.

The Moore monopolar hemiarthroplasty is useful in the management of patients with femoral neck fractures, but long-term results may be associated with acetabular cartilage degeneration and hip pain. The authors report a case of long-term function of a Moore hemiarthroplasty. A 61-year-old woman sustained a fracture of the neck of the femur, which was treated initially with pinning. One year later, because the operation had failed, the patient underwent a Moore hemiarthroplasty. The prosthesis functioned well for 32 years, when she experienced increasing pain in the groin and a decreasing range of hip motion. Radiologic examination showed thinning of the acetabular cartilage so a total hip arthroplasty was performed. This case demonstrates that a unipolar arthroplasty is capable of long-term function, and with current improvements in stem fixation improved longevity can be expected.

Female↗
PubMed1993

Extraction strength of cannulated cancellous bone screws.

The purpose of this study was to determine whether the alterations in the relative dimensions of thread and core diameter that accompany cannulation of cancellous bone screws affect their holding strength. The screws were inserted in bovine femoral cancellous bone and mounted in the load train of a materials testing system. They were then extracted under servo-hydraulic displacement control. The tests were repeated in synthetic cancellous material. From the corresponding load-displacement histories, the maximum force values attained were determined as the screws' holding strengths. The results of tests from 17 matched pairs of bovine femora, and of 15 tests of each screw in synthetic material, were recorded. No significant differences in extraction strength between 7.0-mm cannulated and 6.5-mm standard cancellous bone screws were found. Based on tests in the bovine femur and synthetic cancellous material, this study showed that the extraction strength of cancellous bone screws is not altered by the changes in thread-to-core ratio accommodating cannulation.

Animals↗
PubMed1992

Control of interfragmentary micromotion in Ilizarov distractional osteogenesis.

Growth of the regenerate is affected by various factors during the course of Ilizarov distractional osteogenesis. One of the chief biomechanical factors that influences the quality and rate of bone formation is fixator stiffness. A four-ring Ilizarov apparatus was configured around a synthetic tibia. In a series of trials involving a uniform axial load, different transfixing wire tensions, and the separation of paired proximal and distal rings, fragment displacement was measured. Preliminary results suggest that the effect produced by the distraction of ring pairs on interfragmentary micromotion is as significant as pretensioning of the wires.

Biomechanical Phenomena↗
PubMed1990

Force and stiffness changes during Ilizarov leg lengthening.

Biomechanical considerations of limb lengthening procedures are fundamental to their clinical outcome. The purpose of this study was to determine the relationships among force, stiffness, and distracted length in a patient whose leg was lengthened 50 mm with the Ilizarov procedure. A modified Ilizarov apparatus with force transducers in its three columns was surgically applied to the left tibia of an 11-year-old female patient after corticotomy of the proximal metaphysis. The leg was distracted 0.25 mm four times daily for 50 days, commencing six days after surgery. At approximately weekly intervals, forces at rest were recorded before and after distraction. Resting predistractional force magnitudes increased almost linearly during the first three weeks of lengthening, from 49 N to 223 N. The rate of increase slowed markedly thereafter with a further force increase of 11 N in the next three weeks. The stiffness of the limb, derived from the change in force accompanying the 0.25-mm change in length, increased by approximately 3.9%/mm of distracted length with 95% confidence limits of 6.8% and 0.9%. These results show marked differences from the nonlinearly increasing force-displacement relationship during in vitro limb distraction.

Biomechanical Phenomena↗
PubMed1988

Osteochondritis dissecans of the dome of the talus. Computed tomography scanning in diagnosis and follow-up.

From 1977 through 1985, thirty-two patients were treated for osteochondritis dissecans of the dome of the talus. The diagnosis was established in two-thirds of the patients using ordinary roentgenograms, but it was established in all of them using computed tomography scans. After a mean length of follow-up of about five years, the results of surgical treatment were significantly better than those of conservative treatment. For twenty patients, computed tomography scans were superior to roentgenograms in showing healing of the lesion. We concluded that computed tomography is useful not only for diagnosis--that is, in determining the extent and precise location of the lesion--but also for follow-up.

Adolescent↗
PubMed1985

Efficacy of single- versus multiple-dose clotrimazole therapy in the management of vulvovaginal candidiasis.

Single-dose treatment of vulvovaginal candidiasis with a 500 mg clotrimazole vaginal tablet was compared to 3-day treatment with two 100 mg vaginal tablets administered daily in 115 patients enrolled in a double-blind trial, 101 of whom were evaluated for efficacy. Patients with clinically and mycologically active disease were treated (visit 1) and examined at 5 to 10 days (visit 2) and again at least 27 days (visit 3) post treatment. At visit 2, mycologic tests and clinical examinations were negative in 37 of 48 patients receiving single-dose treatment (77%) and in 47 of 53 patients receiving 3-day treatment (89%). Corresponding results for visit 3 were 65% and 74%, respectively. There were no significant differences in treatment response between groups, and only three patients reported adverse reactions. These data show that single-dose treatment with clotrimazole, 500 mg, is as safe and effective as the more complex 3-day regimen.

Adult↗
PubMed1981

Clinical toxicology of clotrimazole when administered vaginally.

Clotrimazole, a tritylimidazole and a new antimicrobial agent, produced itching and irritation of the vulva and vaginal area in less than 1% of the population (N = 131) studied. No abdominal cramps, headache or lightheadedness, nausea, vomiting, and diarrhea were observed when 200 mg of clotrimazole was inserted deep in the vagina for several days.

Candidiasis↗