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Biomedical subjects

J Newman

Publications and source records attributed to J Newman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Laser hair removal: a review and report on the use of the long-pulsed alexandrite laser for hair reduction of the upper lip, leg, back, and bikini region.

BACKGROUND: The mechanism and permanence of laser-assisted hair removal remains a formidable task in the medical community. OBJECTIVE: The purpose of this study was to determine the safety and long-term efficacy of the long-pulsed or normal mode alexandrite infrared laser for hair depilation. METHODS: Beginning in October 1996, a total of 31 anatomic sites on 22 patients ranging in age from 25 to 59 years (mean 42 years) were evaluated to assess hair removal. Treatment sites included 17 upper lips, 9 legs, 2 backs, and 3 bikini regions. Eligible patients were of Fitzpatrick skin types I-III. Patients were treated using the long-pulsed alexandrite infrared laser at 755 nm, single-pulse technique, 10 mm spot size, 10% overlap, pulse durations of 5, 10, and 20 msec, and a fluence of 20 J/cm2. Subjective patient improvement and objective, blinded graded improvement was assessed at 1, 2, 3, and 6 months. RESULTS: Objective blinded grading at 6 months revealed that hair reduction varied both with the pulse duration and anatomic location. Maximum reductions observed were 40%, 56%, 50%, and 15% for the lip, leg, back, and bikini areas, respectively. Upper lip hair reduction increased from 40% to 54% at 6 months when a second treatment was performed 8 weeks after the initial treatment. CONCLUSION: The long-pulsed alexandrite laser is safe and effective in reducing hair growth. Treatment efficacy varies with the anatomic location, pulse duration, and number of treatments. A single-pulse technique utilizing a 10 msec pulse duration at 20 J/cm2 produced the greatest hair reduction. No permanent adverse effects occurred on skin types I-III at the parameters tested.

Adult↗
PubMed1999

Combined CO2/erbium:YAG laser resurfacing of peri-oral rhytides and side-by-side comparison with carbon dioxide laser alone.

BACKGROUND: Laser resurfacing of facial rhytids has become a popular treatment option for many patients with wrinkles, photoaging, and acne scarring. Laser wavelength options and optimization of techniques continue to evolve in an attempt to shorten the healing phase associated with laser skin resurfacing. OBJECTIVE: To prospectively study the clinical effects of pulsed carbon dioxide (CO2) laser resurfacing of facial rhytids used alone, compared with a combination of CO2 and the pulsed Erbium:YAG (Er:YAG) laser. METHODS: Forty treatment sites on 20 patients were randomized and evaluated following treatment of the upper lip region with a combination of CO2 laser resurfacing alone or with the same CO2 laser treatment followed by 3 passes with the Er:YAG laser. Patient diaries were maintained to assess erythema, crusting, pain, itching, swelling, pigmentary changes, and the day of first make-up application. Blinded objective grading of improvement was independently assessed by 4 blinded observers at time intervals 3, 6, and 10 days, and 1, 2, and 4 months. Chromometer measurements of erythema were also analyzed and percentage moisture recorded. RESULTS: Subjectively, all patients reported, on average, 10 days of redness and 2.4 days of pain, with no significant difference noted between the two procedures. On average, patients were able to apply make-up 5.5 days postoperatively, regardless of which procedure used. However, the combined CO2/Er:YAG laser treatment patients experienced reduced duration of crusting, compared to the patients treated with CO2 alone. The duration of crusting was reduced on average from 7.4 to 6.5 days, and also the duration of itching was reduced in patients receiving combined treatment from 5.5 to 4.8 days. Chromometer measurements noted no significant difference between techniques in the rate of resolution of erythema. Blinded objective grading revealed that crusting was reduced on average from 7.2 to 6.0 days, and swelling was reduced from 6.3 to 6.0 days in patients receiving the combined procedure. No cases of permanent hyperpigmentation, hypopigmentation, or scarring occurred in any patients. CONCLUSION: The addition of the Er:YAG laser following CO2 laser resurfacing reduces the duration of crusting, swelling, and itching postoperatively. Medium to deep (Grade III) facial rhytids were improved by 70% with both procedures with no significant difference noted between techniques.

Adult↗
PubMed1998

Structure of translation initiation factor 5A from Pyrobaculum aerophilum at 1.75 A resolution.

BACKGROUND: Translation initiation factor 5A (IF-5A) is reported to be involved in the first step of peptide bond formation in translation, to be involved in cell-cycle regulation and to be a cofactor for the Rev and Rex transactivator proteins of human immunodeficiency virus-1 and T-cell leukemia virus I, respectively. IF-5A contains an unusual amino acid, hypusine (N-epsilon-(4-aminobutyl-2-hydroxy)lysine), that is required for its function. The first step in the post-translational modification of lysine to hypusine is catalyzed by the enzyme deoxyhypusine synthase, the structure of which has been published recently. RESULTS: IF-5A from the archebacterium Pyrobaculum aerophilum has been heterologously expressed in Escherichia coli with selenomethionine substitution. The crystal structure of IF-5A has been determined by multiwavelength anomalous diffraction and refined to 1.75 A. Unmodified P. aerophilum IF-5A is found to be a beta structure with two domains and three separate hydrophobic cores. CONCLUSIONS: The lysine (Lys42) that is post-translationally modified by deoxyhypusine synthase is found at one end of the IF-5A molecule in an turn between beta strands beta4 and beta5; this lysine residue is freely solvent accessible. The C-terminal domain is found to be homologous to the cold-shock protein CspA of E. coli, which has a well characterized RNA-binding fold, suggesting that IF-5A is involved in RNA binding.

Amino Acid Sequence↗
PubMed1998

A nondenaturing purification scheme for the DNA-binding domain of poly(ADP-ribose) polymerase, a structure-specific DNA-binding protein.

Poly(ADP-ribose) polymerase (PARP) is thought to be involved in DNA repair given its ability to recognize and bind to DNA strand breaks. During apoptosis, PARP is proteolytically cleaved into two stable fragments, the N-terminal 25-kDa DNA-binding domain (DBD) and the 85-kDa fragment containing the automodification and catalytic domains. To understand the DNA-binding properties of PARP, we expressed a recombinant hexahistidine tagged protein (His-DBD) in Escherichia coli. We modified expression to facilitate protein folding by including zinc and reducing the induction temperature. Properly folded, the DNA-binding domain of PARP binds to single- and double-stranded DNA in a structure-specific manner. To eliminate contamination with bacterial DNA that occurred during the purification process, a purification procedure was developed to produce DNA-free protein. In addition, to remove the hexahistidine tag from the recombinant protein, thrombin cleavage was carried out while the recombinant protein was bound to a DNA column. This procedure stabilized the recombinant protein and resulted in nearly 100% cleavage with no appreciable loss to unwanted proteolytic degradation. This nondenaturing purification scheme results in high-quality, native PARP-DBD for use in structural and biochemical studies.

Amino Acid Sequence↗
PubMed1998

Severing of F-actin by the amino-terminal half of gelsolin suggests internal cooperativity in gelsolin.

Gelsolin is a Ca2+-regulated actin-binding protein that can sever, cap, and nucleate growth from the pointed ends of actin filaments. In this study we have measured the binding of the amino-terminal half of gelsolin, G1-3, to pyrene-labeled F-actin as a function of Ca2+ concentration. The rate of binding is shown to be dependent on micromolar concentrations of Ca2+. Independent experiments demonstrate that conformational changes in G1-3 are induced by micromolar concentrations of Ca2+. Titrations of pyrene-F-actin with G1-3 and gelsolin show that the quenching of pyrene fluorescence is identical in extent and stoichiometry for both G1-3 and gelsolin. In contrast, severing of F-actin by G1-3 is found to be much less efficient than is severing by gelsolin. In experiments in which F-actin severing is quantitatively measured, the filament number is found to be proportional to the 1.35 power of the G1-3 concentration. This deviation from linearity may be explained by cooperativity; the binding of two G1-3 molecules in close proximity may lead to cooperative severing of the polymer, thus increasing the severing efficiency. This model is supported by experiments that show that the efficiency of G1-3 severing of F-actin increases with increasing G1-3:F-actin ratios. Extrapolating from these results, we conclude that G4-6, the carboxyl-terminal half of gelsolin, has an active role in the severing of F-actin by intact gelsolin. Whereas F-actin severing by G1-3 is enhanced by cooperative binding of two separate G1-3 molecules, cooperativity is inherent to intact gelsolin because the cooperative partners are covalently linked.

Actins↗
PubMed1998

Ca2+ regulation of gelsolin activity: binding and severing of F-actin.

Regulation of the F-actin severing activity of gelsolin by Ca2+ has been investigated under physiologic ionic conditions. Tryptophan fluorescence intensity measurements indicate that gelsolin contains at least two Ca2+ binding sites with affinities of 2.5 x 10(7) M-1 and 1.5 x 10(5) M-1. At F-actin and gelsolin concentrations in the range of those found intracellularly, gelsolin is able to bind F-actin with half-maximum binding at 0.14 microM free Ca2+ concentration. Steady-state measurements of gelsolin-induced actin depolymerization suggest that half-maximum depolymerization occurs at approximately 0.4 microM free Ca2+ concentration. Dynamic light scattering measurements of the translational diffusion coefficient for actin filaments and nucleated polymerization assays for number concentration of actin filaments both indicate that severing of F-actin occurs slowly at micromolar free Ca2+ concentrations. The data suggest that binding of Ca2+ to the gelsolin-F-actin complex is the rate-limiting step for F-actin severing by gelsolin; this Ca2+ binding event is a committed step that results in a Ca2+ ion bound at a high-affinity, EGTA-resistant site. The very high affinity of gelsolin for the barbed end of an actin filament drives the binding reaction equilibrium toward completion under conditions where the reaction rate is slow.

Actins↗
PubMed1998

Mammography screening among California Medicare beneficiaries: 1993-1994.

BACKGROUND: Over half of all breast cancer deaths occur among women 65 years of age or older. However, mammography screening decreases with increasing age, despite better survival rates for tumors detected early. METHODS: Health Care Financing Administration data from 1993 and 1994, and 1990 United States Census data were used to assess the impact of race, age, Medicaid coverage, and community-level socioeconomic indices on mammography screening for over 800,000 California Medicare beneficiaries. RESULTS: Women who were African American, older, or had Medicaid coverage were significantly less likely to have a biennial mammogram than their counterparts. Women living in areas with fewer college educated residents, with a higher proportion of Mexican or Asian residents had lower use of mammography. However, African-American and Caucasian women with Medicaid coverage had equally low mammography rates (AOR = 1.01, 95% CI .97-1.04), while African-American women with and without Medicaid had similarly low mammography rates (AOR = .96, 95% CI .92-1.01). CONCLUSIONS: Despite dual coverage, Medicare beneficiaries enrolled in Medicaid had few mammograms. African-American Medicare beneficiaries, with and without Medicaid, had low mammography rates. Intervention efforts should be targeted toward these women.

Black or African American↗
PubMed1998

Re-examination of factors associated with expansion of CGG repeats using a single nucleotide polymorphism in FMR1.

In at least 98% of fragile X syndrome cases, the disease results from expansion of the CGG repeat in the 5' end of FMR1. The use of microsatellite markers in the FMR1 region has revealed a disparity of risk between haplotypes for CGG repeat expansion. Although instability appears to depend on both the haplotype and the AGG interspersion pattern of the repeat, these factors alone do not completely describe the molecular basis for the linkage disequilibrium between normal and fragile X chromosomes, in part due to instability of the marker loci themselves. In an effort to better understand the mechanism of dynamic mutagenesis, we have searched for and discovered a single nucleotide polymorphism in intron 1 of FMR1 and characterized this marker, called ATL1, in 564 normal and 152 fragile X chromosomes. The G allele of this marker is found in 40% of normal chromosomes, in contrast to 83% of fragile X chromosomes. Not only is the G allele exclusively linked to haplotypes over-represented in fragile X syndrome, but G allele chromosomes also appear to transition to instability at a higher rate on haplotypes negatively associated with risk of expansion. The two alleles of ATL1 also reveal a highly significant linkage disequilibrium between unstable chromosomes and the 5' end of the CGG repeat itself, specifically the position of the first AGG interruption. The data expand the number of haplotypes associated with FMR1 and specifically allow discrimination, by ATL1 alleles, of single haplotypes with differing predispositions to expansion. Such haplotypes should prove useful in further defining the mechanism of dynamic mutagenesis.

Adenine Nucleotides↗
PubMed1998

Accelerated laser resurfacing wound healing using a triad of topical antioxidants.

BACKGROUND: The speed of wound healing and the duration of erythema are the primary complaints after laser skin resurfacing. Antioxidants have been shown to enhance the healing of wounds by reducing free radical damage. Reepithelialization is also enhanced by the moist environment produced by occlusive dressings. OBJECTIVE: This study was conducted to compare two occlusive agents: white petrolatum and "melting" petrolatum. Another arm of the study evaluated the use of melting petrolatum with and without a triad of topical antioxidants (TTA). RESULTS: Plain white petrolatum proved superior to melting petrolatum in time required for reepithelialization as well as in discomfort. Crusting and pain were decreased with white petrolatum but duration of erythema was equivalent. Wound healing was enhanced when TTA was added. Time for reepithelialization, duration of crusting and scabbing, pain, redness, and swelling were decreased when TTA was added to topical therapy. CONCLUSION: TTA compound enhances and hastens wound healing. White petrolatum as a base occlusive vehicle shortens reepithelialization compared with "melting" petrolatum.

Administration, Cutaneous↗
PubMed1998

Comparative study of the clinical effectiveness of a pyrethrin-based pediculicide with combing versus a permethrin-based pediculicide with combing.

In a randomized, evaluator-blinded clinical trial, 190 patients were treated for Pediculus humanus capitis infestations with a pyrethrin-piperonyl-butoxide pediculicide (RID; Py-PB) and a permethrin pediculicide (NIX; PM). A total of 160 patients were evaluable for nit-combing speed, 156 patients were evaluable for efficacy at day 7, and 150 patients were evaluable for efficacy at day 14. Both Py-PB and PM showed 100% efficacy at day 7. At day 14, one patient in the PM group had an apparent reinfestation. The Py-PB group had significantly lower mean combing times (P=0.04), but because the PM group had more nits, the two groups were not significantly different in combing speed expressed as seconds per nit. Multiple regression and covariance analyses suggested that the greater speed of the Py-PB comb might have been masked by this baseline difference. Three patients had mild adverse experiences (Py-PB: erythema, PM: erythema and tingling sensation). No patients were removed from the study because of adverse events. In conclusion, this controlled clinical study demonstrated that both Py-PB and PM provided 100% efficacy following a single application. Differences attributable to comb design favored the Py-PB "rake" comb, but this requires additional evaluation and confirmation.

Child↗
PubMed1998

Assessment of functional ability in patients with scleroderma: a proposed new disability assessment instrument.

OBJECTIVE: To develop a simple assessment of functional ability in patients with scleroderma and to examine its reliability both as a patient self-administered instrument and when administered by a trained observer. METHODS: An 11 item, 4 grade, functional assessment questionnaire was developed after extensive consultation with patients, physiotherapists (PT), and occupational therapists (OT) with the aim of including all functional areas of relevance. The instrument was self-administered by patients after an interval of 7 days. In the interval, the patients were assessed using the same instrument by direct observation from both a PT and an OT. Forty-seven patients with scleroderma, of varying severity, were recruited from 2 centers. Results were similar for both centers and data were pooled for analysis. RESULTS: Agreement between the patients' first and 2nd assessment was good for all questions (estimated kappas 0.69 to 0.94) with no evidence of an order effect. Agreement was also good between therapists (estimated kappas 0.47 to 0.81). There was poor agreement between patients and therapists, with patients rating their disability substantially higher compared to the standardized therapist assessment. CONCLUSION: This assessment schedule has high face and content validity and has excellent reliability both between trained therapists and within patients over a short time period. Its administration either as a self-report or by a therapist depends, in part, on the type of investigation undertaken.

Disability Evaluation↗
PubMed1997

Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.

We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.

Benzhydryl Compounds↗
PubMed1997

Diagnosis and treatment of Helicobacter pylori infection among California Medicare patients.

BACKGROUND: Antibiotic treatment of Helicobacter pylori infection in active peptic ulcer disease has been demonstrated to speed ulcer healing, reduce the risk of rebleeding, and prevent long-term recurrence. The objective of this study was to determine whether Medicare patients with peptic ulcer disease who are admitted to acute care hospitals are being tested or treated for H pylori infection as recommended by a National Institutes of Health consensus panel. METHODS: The study was designed as a retrospective medical records survey. From the Medicare National Claims History File, all persons 65 years and older admitted to California fee-for-service hospitals for peptic ulcer disease in 1994 were identified. A random sample of 600 claims was selected for review. After exclusions, 524 patients were eligible for study. The main outcome measures were (1) the proportion of patients who were tested for H pylori infection by 1 of the 5 available methods (histopathologic study, urease assay, microbiologic culture, serum antibody testing, or urea breath test) and (2) the proportion who were treated with antibiotics (amoxicillin, tetracycline, clarithromycin, or metronidazole) for H pylori infection. RESULTS: Thirty-nine percent of patients with peptic ulcer disease were tested for H pylori infection and 3% were treated empirically. Only 47% of the patients who had a positive diagnostic test result for H pylori were treated with antibiotics. CONCLUSION: Because diagnosis and treatment of H pylori infection has been demonstrated to improve outcomes and decrease expenses, the data indicate a substantial opportunity to improve the care of elderly Medicare patients with peptic ulcer disease.

Aged↗
PubMed1997

Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: positioning of a highly mobile antigenic loop.

Data from cryo-electron microscopy and X-ray crystallography have been combined to study the interactions of foot-and-mouth disease virus serotype C (FMDV-C) with a strongly neutralizing monoclonal antibody (mAb) SD6. The mAb SD6 binds to the long flexible GH-loop of viral protein 1 (VP1) which also binds to an integrin receptor. The structure of the virus-Fab complex was determined to 30 A resolution using cryo-electron microscopy and image analysis. The known structure of FMDV-C, and of the SD6 Fab co-crystallized with a synthetic peptide corresponding to the GH-loop of VP1, were fitted to the cryo-electron microscope density map. The SD6 Fab is seen to project almost radially from the viral surface in an orientation which is only compatible with monovalent binding of the mAb. Even taking into account the mAb hinge and elbow flexibility, it is not possible to model bivalent binding without severely distorting the Fabs. The bound GH-loop is essentially in what has previously been termed the 'up' position in the best fit Fab orientation. The SD6 Fab interacts almost exclusively with the GH-loop of VP1, making very few other contacts with the viral capsid. The position and orientation of the SD6 Fab bound to FMDV-C is in accord with previous immunogenic data.

Antibodies, Monoclonal↗
PubMed1997

Studies on the structure, regulation, and pathogenic potential of anti-dsDNA antibodies.

Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights into how and why these antibodies arise in systemic lupus erythematosus. In this review we discuss the experimental approaches that have been used by our laboratory to study these autoantibodies. Structure/function analyses including site-directed mutagenesis have helped characterize the molecular genetics of anti-dsDNA antibodies, and more recently peptide libraries have been used to define molecular motifs that these antibodies bind. Most of the pathogenic anti-dsDNA antibodies observed in lupus are somatically mutated. We demonstrated in vitro and in vivo that anti-bacterial antibodies can mutate to acquire specificity for dsDNA. Furthermore, using a fusion partner constitutively expressing bcl-2, NSO(bcl-2), we have shown the existence of anergic or preapoptotic B cells making antibodies that cross-react with both bacterial antigen and dsDNA. Whether defects in the regulation of these antibodies might contribute to serum expression of anti-dsDNA antibodies in some individuals remains unknown. A major emphasis of this review is the regulation of anti-dsDNA antibodies in a transgenic mouse model harboring the gene for the heavy chain of a pathogenic anti-dsDNA antibody. Nonautoimmune transgenic mice effectively regulate autoreactive B cells by anergy and deletion, while their autoimmune counterparts do not. The vast majority of anergic B cells expressing high-affinity transgenic anti-dsDNA antibody fail to display allelic exclusion of the heavy chain. We postulate that this may be one mechanism that allows them to escape deletion. Comparative studies on light chain usage in both the autoimmune and the nonautoimmune transgenic mouse strains have demonstrated that within the autoreactive B-cell population, there are subsets that are differentially regulated. Ultimately transgenic animals making pathogenic autoantibodies may provide us with a system for testing novel therapies for autoimmune disease.

Animals↗