PubMed Health⌕ Search

Biomedical subjects

A L Simon

Publications and source records attributed to A L Simon.

At least 19 recordsLinked to original sources
PubMed1998

Contribution of domain interface residues to the stability of antibody CH3 domain homodimers.

Dimers of CH3 domains from human IgG1 were used to study the effect of mutations constructed at a domain-domain interface upon domain dissociation and unfolding, "complex stability". Alanine replacement mutants were constructed on one side of the interface for each of the sixteen interdomain contact residues by using a single-chain CH3 dimer in which the carboxyl terminus of one domain was joined to the amino terminus of the second domain via a (G4S)4 linker. Single-chain variants were expressed in Escherichia coli grown in a fermentor and recovered in yields of 6-90 mg L-1 by immobilized metal affinity chromatography. Guanidine hydrochloride-induced denaturation was used to follow domain dissociation and unfolding. Surprisingly, the linker did not perturb the complex stability for either the wild type or two destabilizing mutants. The CH3 domain dissociation and unfolding energetics are dominated by six contact residues where corresponding alanine mutations each destabilize the complex by >2.0 kcal mol-1. Five of these residues (T366, L368, F405, Y407, and K409) form a patch at the center of the interface and are located on the two internal antiparallel beta-strands. These energetically key residues are surrounded by 10 residues on the two external beta-strands whose contribution to complex stability is small (three have a Delta DeltaG of 1.1-1.3 kcal mol-1) or very small (seven have a Delta DeltaG of </=0.7 kcal mol-1). Thus, at the center of the CH3 structural interface there is a small "functional interface" of residues that make significant contributions to complex stability.

Alanine↗
PubMed1996

Long-term oral acyclovir therapy. Effect on recurrent infectious herpes simplex keratitis in patients with and without grafts.

PURPOSE: To evaluate the efficacy of long-term oral acyclovir therapy in reducing recurrences of dendritic or geographic herpes simplex keratitis (HSK). METHODS: Thirteen patients with a history of frequently recurring HSK were followed before (mean, 27 months) and during long-term systemic acyclovir, and eight were followed after the acyclovir was discontinued. RESULTS: Treatment ranged from 8.5 to 62 months (mean, 34 months). During treatment, the number of recurrences per month decreased from 0.15 to 0.03, and the average duration of relapses decreased from 12.6 to 7.8 days. Recurrences correlated with daily doses of oral acyclovir of 800 mg or less, intraocular surgery within 6 weeks of initiating treatment, and discontinuation of therapy against medical advice. CONCLUSION: The results of this small study appear to demonstrate the efficacy of long-term oral acyclovir in prophylaxis of recurrent epithelial herpes simplex infection: therapeutic doses of oral acyclovir reduce both the rate and duration of recurrences of infectious herpetic keratitis. A multicenter, double-masked, placebo-controlled study is indicated.

Acyclovir↗
PubMed1987

Flow cytometric analysis of relative mean DNA content of urogenital cancer cells in fresh and paraffin-embedded materials.

The relative mean DNA content calculation was performed by flow cytometry on single cell suspensions prepared from fresh and paraffin-embedded specimens of 10 patients with surgically resected urogenital cancer. Samples were processed by a modified method of Hedley et al. including two hours of pepsinizing time, ribonuclease digestion, and propidium iodide staining. The mean DNA content which is a quantitative description of flow cytometric characteristics was significantly correlated between the fresh and paraffin-embedded materials (n = 10, r = 0.869, p less than 0.01). This method allows for the objective, retrospective analysis of DNA content in relation to diagnosis and prognosis of urogenital cancer.

DNA, Neoplasm↗
PubMed1983

Juxtaductal aortic coarctation. Analysis of 84 patients studied hemodynamically, angiographically, and morphologically after age 1 year.

Although many studies of juxtaductal coarctation of the aorta have been reported, none has correlated clinical, hemodynamic, angiographic, anatomic, and operative findings. Of 84 patients (62 male and 22 female; age range, 1 to 49 years [mean 17]), all had murmurs; 76 had absent, diminished, or delayed femoral pulsations; 50 had cuff systolic blood pressures in the arm greater than 140 mm Hg, and 30 had diastolic pressures greater than 90 mm Hg. The average pressure gradients (mm Hg) by direct measurements above and below the coarctation in 35 patients were peak systolic, 45; mean, 17; and diastolic, 5. Rib notching, visible in chest roentgenograms in 43 patients, correlated directly with age and inversely with the diameter of the coarctation. Moderate or marked cardiomegaly by radiograph was present in only 1 of 48 patients with isolated coarctation and in 17 of 36 with associated cardiovascular malformations. Electrocardiograms were abnormal in more than two thirds of patients with associated anomalies, but were normal in more than three fourths of those with isolated coarctation. In 70 excised, serially sectioned coarctations the aortic lumens were completely occluded in 4 patients, up to 0.5 mm in internal diameter in 22 patients, from 0.6 to 2 mm in 26 patients, from 2.1 to 5 mm in 14, and greater than 5 mm in 4, and correlated directly with lumens measured angiographically. The most significant anatomic factor causing the coarctation was invagination of the media from the posterior aortic wall, but intimal proliferation (jet lesion) at and immediately distal to the invagination contributed to the narrowing. Three (each with associated anomalies) of 70 patients died early after coarctation repair. Systolic or diastolic blood pressures decreased early postoperatively in 58 (87%) of 67 surviving patients, and both pressures decreased in 42 (63%). Late postoperatively (mean follow-up, 4.7 years), the systolic blood pressure remained elevated in 25% of patients.

Adolescent↗
PubMed1975

Catheter positions in congenital cardiac malformations.

Biplane cineangiocardiograms were examined from a population of patients with diverse forms of congenital heart disease and examples were selected to illustrate catheter positions which may help define and elucidate the anatomy of simple and complex cardiac lesions. Familiarity with the appearance of these typical and atypical catheter positions may be of considerable aid in the course of hemodynamic study and in the evaluation of cineangiocardiograms. The editors suggest that each figure be evaluated as an unknown before reading the caption.

Angiocardiography↗