Search

The effect of high pressure on the log reduction of six strains of Escherichia coli O157:H7 and five serovars of Salmonella enterica was investigated in tryptic soy broth, sterile distilled water, and commercially sterile orange juice (for Salmonella) and apple cider (for E. coli). Samples were subjected to high-pressure processing treatment at 300 and 550 MPa for 2 min at 6 degrees C. Samples were plated onto tryptic soy agar directly after pressurization and after being held for 24 h at 4 degrees C. At 300 MPa, little effect was seen on E. coli O157:H7 strains, while Salmonella serovars varied in resistance, showing reductions between 0.26 and 3.95 log CFU/ml. At 550 MPa, E. coli O157:H7 strains exhibited a range of reductions (0.28 to 4.39 log CFU/ml), while most Salmonella populations decreased beyond the detection limit (> 5-log CFU/ml reduction). The most resistant strains tested were E. coli E009 and Salmonella Agona. Generally, bacterial populations in fruit juices showed larger decreases than did populations in tryptic soy broth and distilled water. E. coli O157:H7 cultures held for 24 h at 4 degrees C after treatment at 550 MPa showed a significant log decrease as compared with cultures directly after treatment (P < or = 0.05), while Salmonella serovars did not show this significant decrease (P > 0.05). All Salmonella serovars tested in orange juice treated at 550 MPa for 2 min at 6 degrees C and held for 24 h showed a > 5-log decrease, while E. coli O157:H7 strains require a higher pressure, higher temperature, longer pressurization, or a chemical additive to achieve a 5-log decrease.

Curli fibers are produced by some Escherichia coli cells in response to environmental stimuli. These extracellular proteins enhance the cell's ability to form biofilms on various abiotic surfaces. E. coli 0157:H7 cells readily attach to a variety of fruit and vegetable surfaces. It is not known whether the expression of curli influences the cell's ability to attach to produce surfaces. In this study, the effect of curli expression on the cell's overall hydrophobicity, charge, and ability to attach to cut and whole iceberg lettuce surfaces was examined. All strains, regardless of curli expression, attached preferentially to the cut edges of lettuce (P < 0.05). The curli-producing cells of E. coli 0157:H7 strain E0018 attached in significantly greater numbers to both cut and whole lettuce pieces than did the non-curli-producing E0018 cells (P < 0.05); however, no significant attachment differences were observed between the curli-producing and non-curli-producing cells of E. coli 0157:H7 strains 43894 and 43895. All curli-producing E. coli 0157:H7 strains were significantly more hydrophobic (P < 0.01); however, no association between the cells' hydrophobic characteristics and lettuce attachment was observed. Overall surface charge of the cells did not differ among strains or curli phenotypes. Results indicate that overall hydrophobicity and cell charge in E. coli 0157:H7 strains do not influence attachment to iceberg lettuce surfaces. The presence of curli may not have any influence on attachment of E. coli 0157:H7 cells to produce items. Additional factorsmay influence the attachment of E. coli 0157:H7 to plant surfaces and should be further examined.

Analyses of three waves (6 years) of the National Longitudinal Survey of Adolescent Health data explored the prevalence and stability of sexual orientation and whether these two parameters varied by biologic sex, sexual orientation component (romantic attraction, sexual behavior, sexual identity), and degree of component. Prevalence rates for nonheterosexuality varied between 1 and 15% and depended on biologic sex (higher among females), sexual orientation component (highest for romantic attraction), degree of component (highest if "mostly heterosexual" was included with identity), and the interaction of these (highest for nonheterosexual identity among females). Although kappa statistics testing for temporal stability across waves were significant, they failed to reach acceptable levels of agreement and could be largely attributable to the stability of opposite-sex rather than same-sex attraction and behavior. Migration over time among sexual orientation components was in both directions, from opposite-sex attraction and behavior to same-sex attraction and behavior and vice versa. To assess sexual orientation, investigators should measure multiple components over time or abandon the general notion of sexual orientation and measure only those components relevant for the research question.

Packaging fishery products under vacuum atmosphere packaging (VAC) and modified atmosphere packaging (MAP) conditions can significantly extend the shelf life of raw, refrigerated fish products. There is considerable commercial interest in marketing VAC and MAP refrigerated (never frozen) raw fish fillets. The objective of this study was to determine if Clostridium botulinum toxin development precedes microbiological spoilage in raw, refrigerated flounder fillets. Aquacultured flounder (Paralichthys dentatus) individual fish fillets either were packed with a film having an oxygen transmission rate (OTR) of 3000 cm3 m(-2) 24 h(-1) at 22.8 degrees C or were vacuum packaged or packaged under 100% CO2 with a film having an OTR of 7.8 cm3 m(-2) 24 h(-1) at 21.1 degrees C and were stored at 4 and 10 degrees C. Samples were analyzed by aerobic plate count (APC) for spoilage and qualitatively for botulinum toxin with a mouse bioassay. The results demonstrate that flounder fillets (4 degrees C) packaged with a film having an OTR of 3,000 were microbiologically spoiled (APC, > 10(7) CFU/g) on day 15, but there was no toxin formation, even after 35 days of storage. However, at 10 degrees C, toxin production occurred (day 8), but it was after microbial spoilage and absolute sensory rejection (day 5). Vacuum-packaged fillets and 100% CO2 fillets (4 degrees C) packaged with a film having an OTR of 7.8 were toxic on days 20 and 25, respectively, with microbial spoilage (APC, >10(7) CFU/g) not occurring during the tested storage period (i.e., >35 days). At 10 degrees C, in vacuum-packaged flounder, toxin formation coincided with microbiological spoilage (days 8 to 9). In the 100% CO2-packaged fillets, toxin formation occurred on day 9, with microbial spoilage occurring on day 15. This study indicates that films with an OTR of 3,000 can be used for refrigerated fish fillets and still maintain the safety of the product.

The ability of Listeria monocytogenes to attach to various food contact surfaces, such as stainless steel, polypropylene, and rubber compounds, is well documented. The retention of these or other pathogenic bacteria on food contact surfaces increases the risk of transmission to food products. The objective of this study was to compare several methods for quantitative recovery of Listeria monocytogenes from stainless steel surfaces. A cocktail of 4 serotypes of Listeria monocytogenes mixed in equivalent concentrations was inoculated onto type 304 stainless steel coupons in a 2 x 2 cm area. After 1 h exposure, coupons were sampled by one of the following methods: (1) swabbing with a premoistened Dacron swab; (2) rinsing with phosphate-buffered saline; (3) direct contact onto tryptic soy agar containing 0.6% yeast extract (TSA + YE) plates for 10 s; (4) sonication in an ultrasonic water bath (40 kHz); (5) contact with the bristles of a sonicating brush head for 1 min; and (6) indirect contact (2-4 mm distance) with a sonicating brush head for 1 min. The 3 sonication methods yielded higher recovery than the other 3 methods (P < 0.05). Brushing the coupons with the sonicating brush head (contact or noncontact) yielded a recovery level of about 60%. The lowest cell recovery (about 20%) was observed with the swab and direct agar contact methods. After a 12 h exposure, recoveries ranged from 17.4 (brush contact method) to 2% (swab method).

Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma have been considered to represent disorders associated with reaction of the patient's own immune system against self-antigens or body systems. In many such disorders, tissues involved show lesions or morphology indicating destructive inflammatory or reactive features clearly produced by or associated with cell-mediated or antibody-driven reactions of the patient against his own tissues. After an exhaustive search which has stretched back in time for at least the last five decades, we seem to understand how the immune system works better than previously. However, despite the fact that we now understand molecular mechanisms of antibody selection and structure, how the cell-mediated and humoral antibody system is activated in terms of signal peptides and in the context of HLA molecules, we have not yet exactly identified inciting antigens which clearly cause these diseases. The focus recently has shifted towards being able to down-modulate potentially harmful parts of a self-directed inflammatory process by abrogating harmful messenger molecules participating in tissue injury. Following such a path, we may actually alleviate or cure these diseases before eventually identifying their original cause.

Environmental sampling has become increasingly important in the food industry for monitoring the presence of specific pathogens such as Listeria monocytogenes and Salmonella enterica. Several microbiological media are available for storage and transport of environmental samples from the processing plant to the test laboratory. In this study, we quantified the survival of L. monocytogenes, S. Typhimurium, S. Enteritidis, and S. Typhi in environmental sampling media over several time and temperature combinations to determine optimum conditions for transport and storage. A cocktail of L. monocytogenes strains and Salmonella serotypes was separately added to tubes of Dey-Engley (D/E) Neutralizing Broth, Copan SRK solution, and Neutralizing Buffer and incubated at either -4, 4, 10, or 15 degree C. Counts were made of the bacterial load after 0, 12, 24, and 48 h. Neutralizing Buffer and Copan SRK solution were best at maintaining bacterial concentrations at all temperatures. D/E Neutralizing Broth, at 10 and 15 degrees C, allowed significant bacterial growth. This study helped validate the use of these 3 media for environmental sample transport and storage at cold holding temperatures and demonstrated that, at elevated temperatures (>4 degrees C), it is preferable to use Neutralizing Buffer or Copan SRK solution for quantifying microbial recovery.

The vitamin D receptor (VDR) and the human leukocyte antigen (HLA) class II complex affect innate and/or adaptive immunity against Mycobacterium tuberculosis. HLA-DRB1, HLA-DQB1, and VDR gene (VDR) polymorphisms were previously associated with tuberculosis (TB) and are here investigated as candidates for TB susceptibility in the Venda population of South Africa. Genomic DNA from 95 patients with pulmonary tuberculosis (PTB) and 117 ethnically matched, healthy controls were typed for HLA-DRB1, DRB3, DRB4, DRB5, DQB1, and VDR polymorphisms FokI, BsmI, ApaI, and TaqI using polymerase chain reaction-sequence specific primers (PCR-SSP). Allele and haplotype frequencies were calculated by the estimator maximum (EM) algorithm. DRB1*1302 phenotype was significantly associated with TB occurring at a significantly higher allele frequency in cases than controls and found in haplotype with DQB1*0602/3. DQB1*0301-0304 phenotype was significantly associated with TB and found in haplotype with DRB1*1101-1121, showing significant linkage disequilibrium (LD) in both cases and controls. Only DRB1*1101-1121-DQB1*05 was significantly associated with TB based on the sequential Bonferroni p value. VDR SNP phenotypes were not associated with TB, but the haplotype F-b-A-T significantly protected from TB. In conclusion, common African HLA-DRB1 and -DQB1 variants, previously associated with protection from malaria and hepatitis B/C virus persistence, predispose the Venda to TB, whereas the proposedly active VDR haplotype F-b-A-T showed significant protection.

Failures of endosseous dental implants are rare and tend to cluster in patients with common profiles or risk factors. Clinical trials indicate that factors related to implant devices, anatomy, occlusion,systemic health or exposures, microbial biofilm, host immuno-inflammatory responses, and genetics may increase the risk for im-plant complications or loss. In general, factors associated with the patient appear more critical in determining risk for implant failure than those associated with the implant itself. Several risk factors can be modified. For example, the patient can modify smoking and the clinician can modify implant selection, site preparation,and loading strategy. In identifying these factors and making appropriate interventions, clinicians can enhance success rates while improving oral function, esthetics, and patient well-being.

Using 6-year longitudinal data from the National Longitudinal Survey of Adolescent Health (Add Health) and multiple measures of puberty as it occurs and of sexual orientation (romantic attraction, sexual identity), the present study attempted to replicate previous research which reported that homosexuals and heterosexuals differed in their age of pubertal onset. The study hypotheses were not confirmed for either males or females: on most pubertal measures, same-sex oriented groupings did not differ from heterosexuals. The only significant findings regarding homosexual males indicated that they were more likely to report having a later rather than an earlier onset of puberty, and the significant findings regarding homosexual females were contradictory--they tended to have an earlier onset of puberty. These findings are attributed to methodological improvements in the present study that reduced retrospective bias, used multiple indicators of sexual orientation and puberty timing, and assessed less eroticized measures of puberty.

Background: Nitric oxide is a free radical produced in host tissues by constitutive and inducible forms of the enzyme nitric oxide synthase. Nitric oxide plays physiological roles, but it is also involved in the pathophysiology of several inflammatory conditions, including arthritis, ulcerative colitis, and circulatory shock. Local increases in inducible nitric oxide synthase (iNOS) and reactive nitrogen products have also been demonstrated in humans and animals with periodontal disease. This masked, randomized, placebo-controlled preclinical investigation examined the effect of two mercaptoalkylguanidines, mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED), which are iNOS inhibitors and reactive nitrogen scavenging compounds, on the development of experimental gingivitis in beagle dogs., Methods: Fifteen female, 1-year-old beagles first completed a 2-week dose-escalation experiment during which a maximum tolerated dose was determined for MEG and GED gels. Thereafter, all animals were brought to optimal gingival health by mechanical scaling, followed by rigorous daily toothbrushing over a 4-week washout period. Experimental gingivitis was then induced, with cessation of plaque control and institution of a soft diet over 8 weeks. Beagles randomly received 0.3% MEG, 0.3% GED, or placebo (vehicle) gels, topically applied twice daily to premolar teeth. Gingival inflammation, bleeding tendency, and supragingival plaque were clinically measured at baseline and at 2, 3, 4, 6, and 8 weeks. Comparisons among groups and between group pairs (active versus placebo) were made using Kruskal-Wallis tests., Results: From baseline to day 7, all groups expressed similar indices. Thereafter, significant and time-dependent increases in the plaque index (PI), gingival index (GI), and percentage of bleeding on probing (%BOP) were observed in placebo-treated beagles. Mean GI scores for beagles treated with GED or MEG gels remained at or below baseline levels for the entire treatment period. At weeks 2, 3, 4, and 8, GI scores were significantly lower for MEG and GED groups compared to the placebo group (P<0.05). In addition, MEG and GED gels significantly reduced gingival bleeding responses by 8 weeks (P<0.05). Although placebo-treated beagles demonstrated %BOP scores of 43% at week 8, GED- and MEG-treated beagles exhibited %BOP scores of 21% and 26%, respectively. Since no statistical difference among PI scores was noted for any of the time points, neither mercaptoalkylguanidine appeared to affect supragingival plaque levels., Conclusion: The data from this preclinical study indicate that mercaptoalkylguanidines, topically administered, may significantly reduce experimental gingivitis in the beagle dog.

Objectives: Bone formation during guided tissue regeneration is a tightly regulated process involving cells, extracellular matrix and growth factors. The aims of this study were (i) to examine the expression of cyclooxygenase-2 (COX-2) during bone regeneration and (ii) the effects of selective COX-2 inhibition on osseous regeneration and growth factor expression in the rodent femur model., Material and Methods: A standardized transcortical defect of 5 x 1.5 mm was prepared in the femur of 12 male rats and a closed half-cylindrical titanium chamber was placed over the defect. The expression of COX-2 and of platelet-derived growth factor-B (PDGF-B), bone morphogenetic protein-6 (BMP-6) and insulin-like growth factor-I/II (IGF-I/II) was analyzed at Days 3, 7, 21 and 28 semiquantitatively by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of COX-2 inhibition by intraperitoneal injection of NS-398 (3 mg/kg/day) were analyzed in five additional animals sacrificed at Day 14., Results: Histomorphometry revealed that new bone formation occurred in the cortical defect area as well as in the supracortical region, i.e. region within the chamber by Day 7 and increased through Day 28. Immunohistochemical evidence of COX-2 and PDGF-B levels were observed early (i.e. Day 3) and decreased rapidly by Day 7. BMP-6 expression was maximal at Day 3 and slowly declined by Day 28. In contrast, IGF-I/II expression gradually increased during the 28-day period. Systemic administration NS-398 caused a statistically significant reduction (P<0.05) in new bone formation (25-30%) and was associated with a statistically significant reduction in BMP-6 protein and mRNA expression (50% and 65% at P<0.05 and P<0.01, respectively). PDGF-B mRNA or protein expression was not affected by NS-398 treatment., Conclusion: COX-2 inhibition resulted in reduced BMP-6 expression and impaired osseous regeneration suggesting an important role for COX-2-induced signaling in BMP synthesis and new bone formation.

The structure and functions of the modern human hand are critical components of what distinguishes Homo sapiens from the great apes (Gorilla, Pan, and Pongo). In this study, attention is focused on the trapezium and trapezoid, the two most lateral bones of the distal carpal row, in the four extant hominid genera, representing the first time they have been quantified and analyzed together as a morphological-functional complex. Our objective is to quantify the relative articular and nonarticular surface areas of these two bones and to test whether modern humans exhibit significant shape differences from the great apes, as predicted by previous qualitative analyses and the functional demands of differing manipulative and locomotor strategies. Modern humans were predicted to show larger relative first metacarpal and scaphoid surfaces on the trapezium because of the regular recruitment of the thumb during manipulative behaviors; alternatively, great apes were predicted to show larger relative second metacarpal and scaphoid surfaces on the trapezoid because of the functional demands on the hands during locomotor behaviors. Modern humans were also expected to exhibit larger relative mutual joint surfaces between the trapezoid and adjacent carpals than do the great apes because of assumed transverse loads generated by the functional demands of the modern human power grip. Using 3D bone models acquired through laser digitizing, the relative articular and nonarticular areas on each bone are quantified and compared. Multivariate analyses of these data clearly distinguish modern humans from the great apes. In total, the observed differences between modern humans and the great apes support morphological predictions based on the fact that this region of the human wrist is no longer involved in weight-bearing during locomotor behavior and is instead recruited solely for manipulative behaviors. The results provide the beginnings of a 3D comparative standard against which further extant and fossil primate wrist bones can be compared within the contexts of manipulative and locomotor behaviors.

The recently published genome sequence of Bacillus anthracis Ames has facilitated the prediction of proteins associated with the virulence of this bacterium. The aim of this study was to define reference maps for the extracellular and cytoplasmic proteomes of the avirulent B. anthracis strain UM23C1-2 that are useful for physiological studies and the development of improved vaccines. Using 2-DE and subsequent MALDI-TOF-TOF MS, 64 proteins were identified in the extracellular proteome, only 29 of which were predicted to be exported into the culture medium. The latter included chitinases, proteases, nucleotidases, sulfatases, phosphatases and proteins of unknown function. Of the remaining proteins in the culture medium, 18 were predicted to be associated with the cell wall or anchored on the trans side of the cytoplasmic membrane while 17 other proteins lacked identifiable export signals and were predicted to be cytoplasmic proteins. Among the S-layer proteins, Sap and Eag account for 10% of the total extracellular proteome. Many of the proteins are predicted to contribute to the virulence and antigenic signature of B. anthracis. We have also studied the composition of the cytoplasmic proteome, identifying 300 distinct proteins. The most abundant cytoplasmic proteins are primarily those involved in glycolysis, amino acid metabolism, protein translation, protein folding and stress adaptation. The presence of a variety of proteases, peptidases, peptide binding proteins, as well as enzymes required for the metabolism of amino acids, suggests that B. anthracis is adapted to life in a protein-rich environment rather than the soil. We therefore speculate that proteases and peptidases could be useful targets for the development of improved vaccines. In addition, both of these B. anthracis compartment-specific proteomes can be used as reference maps to monitor changes in the production of secreted and cytosolic proteins that occur, for example, during growth in macrophages.

Clinically apparent renal cell carcinoma that has metastasized to the prostate is a rare finding. When identified, it has been associated with widespread metastatic disease and short-term survival. We present a case of metachronous renal cell carcinoma found only in the prostate with the longest reported interval of 9 years between radical nephrectomy and clinically apparent disease.

The authors examined differences in adolescents' relationships with their parents before and after adolescent first sexual activity. Participants were 13,570 members of the core sample of the National Longitudinal Survey of Adolescent Health (Add Health) Waves 1 and 2. Path analyses examined changes in parent-adolescent closeness, shared activities, and problem-focused interactions associated with changes in sexual activity separately for sons and daughters and for mothers and fathers. Race, religion, age, urbanicity, and parents' education were controls. Results confirm that increased problem-focused interactions and decreased parental closeness and shared activities both precede and follow adolescent sexual activity. Maintaining positive parental relations after adolescent first sexual activity is discussed as a means to reduce risks associated with sex., (2005 APA, all rights reserved)

Objective: To examine the relationship of serum C-reactive protein (CRP) levels to other indicators of disease activity during the course of systemic lupus erythematosus (SLE)., Methods: In 124 patients serum CRP was measured retrospectively by ELISA and in some instances by radial immunodiffusion. Serum CRP levels were compared to laboratory, clinical, and radiographic assessments of disease activity. In many patients, serial CRP levels were measured over months or years to determine whether elevations of serum CRP reflected apparent changes in other disease activity variables. CRP was also measured in lyophilized aliquots of 24 h urine samples from SLE patients and controls with other renal disorders. Parallel determinations of interleukin 6 (IL-6) were made by ELISA in healthy controls and SLE patients., Results: Of the 124 SLE patients studied, most showed elevations in serum CRP levels in the course of their disease. No inverse or direct correlation was noted between serum CRP and levels of nucleosome antigen or serum IgM or IgG anti-DNA antibody. In patients with renal involvement and proteinuria, CRP was often detected in 24-h urine samples. A strong correlation (p < 0.001) was noted between CRP and IL-6 levels in healthy subjects, but no correlation was recorded between serum CRP and IL-6 in SLE., Conclusion: Contrary to previous reports, most patients with SLE in our study showed elevations of serum CRP during the course of their illness, and extremely high serum CRP was recorded in some patients. CRP was also found in concentrated urine samples from patients with renal involvement and often paralleled elevated serum levels. In patients, no correlation was seen between CRP serum levels and serum IL-6, whereas a strong correlation between CRP level and IL-6 was recorded in healthy subjects.

A randomized complete block design with five treatments (100% pale, soft, and exudative-like (PSE-like), 100% PSE-like+1.5% collagen, 100% PSE-like+0.30% κ-/ι-carrageenan, 100% PSE-like+1.5% soy protein concentrate, and 100% Normal) and six replications was utilized to test the effects of meat raw material, turkey collagen (TC), soy protein concentrate (SPC), and carrageenan (CG) on protein functionality in the formulation of chunked and formed turkey breast. Addition of 1.5% SPC and 1.5% TC both decreased (P<0.05) cooking loss and increased (P<0.005) the protein bind of treatments formulated with 100% PSE-like raw material. Purge loss decreased (P<0.05) in PSE-like raw material when 1.5% TC, 1.5% SPC, or 0.30% CG were utilized, and no differences (P>0.05) existed in consumer acceptability among treatments. This research demonstrates the potential to increase the water holding capacity and improve the texture of deli rolls from PSE-like raw material through the incorporation of collagen, soy protein, or carrageenan.

Objectives: Serum C-reactive protein (CRP) has been shown to be a risk predictor for cardiovascular disease. Periodontal treatment reduces elevated CRP levels. The aim of this pilot investigation was to evaluate if dental implants placed after extractions in patients with end-stage periodontitis affect the serum CRP levels., Material and Methods: Serum CRP levels in 10 subjects with end-stage periodontitis were measured prior to tooth extraction and placement of dental implants, and at 3-month intervals for a year post-operatively. Univariate repeated measures analysis of variance was used to estimate and test the changes in CRP levels over time., Results: Mean CRP levels decreased significantly following tooth extraction and replacement with dental implants from 3.45 to 1.55 mg/dl after 12 months (P < 0.01). Six-, 9-, and 12-month post-implant placement mean CRP values were statistically significantly different from the mean pre-operative CRP value (P < 0.01)., Conclusions: The pilot data suggest that extraction of advanced periodontally involved teeth and their replacement with dental implants lead to a decrease in CRP levels, and dental implant placement does not change the lowered CRP levels over a 12-month period.

This paper addresses the problem of adverse pregnancy outcome in relation to periodontal disease. There is compelling evidence that a link exists between pre-term low birth weight (PLBW) and periodontitis. Although 25% to 50% of PLBW deliveries occur without any known aetiology, there is increasing evidence that infection may play a significant role in pre-term delivery. A model explaining the plausible relationship is proposed based upon the concept of infection leading to a cascade of inflammatory reactions associated with pre-term labour and periodontal disease. Current evidence has pointed to an interest in dental intervention studies to control periodontal disease as one of the potential strategies to reduce pre-term labour. This paper reviews the potential association between periodontal infection and adverse pregnancy outcomes.

Inactivation of Escherichia coli O157:H7 suspended in salt solutions (Na(2)PO(4), NaCl, NaNO(3), NH(4)Cl, CaCl(2), and AlCl(3)) at concentrations ranging from 0 to 5% (w/v) by high-intensity ultrasound at two different temperature conditions (ice water bath, 40 degrees C water bath) and three ultrasonic intensity levels (9.5, 21.8, 49.2 W/cm(2)) was determined. Increases in sonication treatment time, intensity, and temperature led to increased lethality of E. coli O157:H7. However, cell lethality, as a function of solute concentration, varied depending upon type of salt. CaCl(2), NaCl, NaNO(3), Na(2)PO(4), and NH(4)Cl had little or no effect on survival of E. coli O157:H7 (<1-log reduction) regardless of other treatment conditions at 9.5 W/cm(2). Concentrations of >0.5% of CaCl(2), NaNO(3), Na(2)PO(4), and NH(4)Cl adversely affected survival (1.0- to 1.6-log reduction) with treatment of 21.8 W/cm(2) in an ice bath and showed greater inactivation (1.2-4.0-log reduction) in the 40 degrees C water bath. Treatment of 49.2 W/cm(2) showed the greatest impact regardless of other parameters. In the 40 degrees C water bath, treatment for 10 min at 49.22 W/cm(2) led to total inactivation for cells suspended in 0.5% NH(4)Cl, 1% CaCl(2), 2% NaCl, 5% Na(2)PO(4), and all concentrations of AlCl(3). Complete inactivation also occurred in an ice bath for 5% AlCl(3), which was shown to be the most effective salt. The most efficient treatment combination was in the 40 degrees C water bath for 10 min at 49.2 W/cm(2) with 5% AlCl(3). Inactivation of E. coli O157:H7 is attributed to cavitation-induced shear forces, reaction of cavitation-generated hydrogen peroxide with microbial cell wall constituents and electrostatic interactions of dissociated salts with cell membranes.

Inactivation of Escherichia coli O157:H7 and Salmonella in apple cider and orange juice treated with ozone was evaluated. A five-strain mixture of E. coli O157:H7 or a five-serovar mixture of Salmonella was inoculated (7 log CFU/ml) into apple cider and orange juice. Ozone (0.9 g/h) was pumped into juices maintained at 4 degrees C, ambient temperature (approximately 20 degrees C), and 50 degrees C for up to 240 min, depending on organism, juice, and treatment temperature. Samples were withdrawn, diluted in 0.1% peptone water, and surface plated onto recovery media. Recovery of E. coli O157:H7 was compared on tryptic soy agar (TSA), sorbitol MacConkey agar, hemorrhagic coli agar, and modified eosin methylene blue agar; recovery of Salmonella was compared on TSA, bismuth sulfite agar, and xylose lysine tergitol 4 (XLT4) agar. After treatment at 50 degrees C, E. coli O157:H7 populations were undetectable (limit of 1.0 log CFU/ml; a minimum 6.0-log CFU/ml reduction) after 45 min in apple cider and 75 min in orange juice. At 50 degrees C, Salmonella was reduced by 4.8 log CFU/ml (apple cider) and was undetectable in orange juice after 15 min. E. coli O157:H7 at 4 degrees C was reduced by 4.8 log CFU/ml in apple cider and by 5.4 log CFU/ml in orange juice. Salmonella was reduced by 4.5 log CFU/ml (apple cider) and 4.2 log CFU/ml (orange juice) at 4 degrees C. Treatment at ambient temperature resulted in population reductions of less than 5.0 log CFU/ml. Recovery of E. coli O157:H7 and Salmonella on selective media was substantially lower than recovery on TSA, indicating development of sublethal injury. Ozone treatment of apple cider and orange juice at 4 degrees C or in combination with mild heating (50 degrees C) may provide an alternative to thermal pasteurization for reduction of E. coli O157:H7 and Salmonella in apple cider and orange juice.

Objective: The quantitative capability of a positron emission tomography scanner for small animal imaging was evaluated in this study., Methods: The microPET P4 (Concorde Microsystems, Knoxville, TN) scanner's capability for dynamic imaging and corrections for radioactive decay, dead time, and attenuation were evaluated. Rat brain and heart studies with and without attenuation correction were compared. A calibration approach to convert the data to nanocuries per milliliter was implemented. Calibration factors were determined using calibration phantoms of 2 sizes with and without attenuation correction. Quantitation was validated using the MiniPhantom (Data Spectrum, Chapel Hill, NC) with hot features (5:1 ratio) of different sizes (4, 6.4, 8, 13, and 16 mm)., Results: The microPET P4 scanner's ability to acquire dynamic studies and to correct for decay, dead time, and attenuation was demonstrated. The microPET P4 scanner provided accurate quantitation to within 6% for features larger than 10 mm. Sixty percent of object contrast was retained for features as small as 4 mm., Conclusions: The microPET P4 scanner can provide accurate quantitation.

In a recently completed case-control epidemiological study, the New Jersey Department of Health and Senior Services (NJDHSS) with support from the Agency for Toxic Substances and Disease Registry (ATSDR) documented an association between prenatal exposure to a specific contaminated community water source and leukaemia in female children. An important and necessary step in the epidemiological study was the reconstruction of the historical water supply strategy of the water distribution system serving the Dover Township area, New Jersey. The sensitivity of solutions to: (1) pressure and pattern factor constraints, (2) allowable operational extremes of water levels in the storage tanks, and (3) the non-uniqueness of the water supply solution are analysed in detail. The computational results show that the proposed approach yields satisfactory results for the complete set of monthly simulations and sensitivity analyses, providing a consistent approach for identifying the historical water supply strategy of the water distribution system. Sensitivity analyses indicated that the alternative strategy obtained from the revised objective function and the variation of constraints did not yield significantly different water supply characteristics. The overall analysis demonstrates that the progressive optimality genetic algorithm (POGA) developed to solve the optimization problem is an effective and efficient algorithm for the reconstruction of water supply strategies in water distribution systems.

The New Jersey Department of Health and Senior Services (NJDHSS), with support from the Agency for Toxic Substances and Disease Registry (ATSDR) conducted an epidemiological study of childhood leukaemia and nervous system cancers that occurred in the period 1979 through 1996 in Dover Township, Ocean County, New Jersey. The epidemiological study explored a wide variety of possible risk factors, including environmental exposures. ATSDR and NJDHSS determined that completed human exposure pathways to groundwater contaminants occurred in the past through private and community water supplies (i.e. the water distribution system serving the area). To investigate this exposure, a model of the water distribution system was developed and calibrated through an extensive field investigation. The components of this water distribution system, such as number of pipes, number of tanks, and number of supply wells in the network, changed significantly over a 35-year period (1962--1996), the time frame established for the epidemiological study. Data on the historical management of this system was limited. Thus, it was necessary to investigate alternative ways to reconstruct the operation of the system and test the sensitivity of the system to various alternative operations. Manual reconstruction of the historical water supply to the system in order to provide this sensitivity analysis was time-consuming and labour intensive, given the complexity of the system and the time constraints imposed on the study. To address these issues, the problem was formulated as an optimization problem, where it was assumed that the water distribution system was operated in an optimum manner at all times to satisfy the constraints in the system. The solution to the optimization problem provided the historical water supply strategy in a consistent manner for each month of the study period. The non-uniqueness of the selected historical water supply strategy was addressed by the formulation of a second model, which was based on the first solution. Numerous other sensitivity analyses were also conducted using these two models. Both models are solved using a two-stage progressive optimality algorithm along with genetic algorithms (GAs) and the EPANET2 water distribution network solver. This process reduced the required solution time and generated a historically consistent water supply strategy for the water distribution system.

To adequately understand the diversity of child and adolescent homoeroticism, a differential developmental trajectories perspective is proposed that integrates recent research about the development of sexual orientation, sexual behavior, and sexual identity. Only the latter two can be altered therapeutically. Biologic theories of homosexuality are reviewed. Homoerotic youth are shown to be similar and dissimilar to heterosexual youth; more variability occurs within than among sexual orientation groups. Contemporary homoerotic youth recognize their sexuality, self-label, and accept their sexuality at earlier ages than previous generations and many are rejecting traditional identity labels. Clinical recommendations offer ways to assess sexual orientation and help patients to achieve acceptance of their sexuality.

Researchers disagree on how to assess adolescent sexual orientation. The relative importance of various dimensions (e.g. attraction, relationships, behavior, self-labeling) is unknown, which calls into question the validity of studies assessing adolescent sexual orientation. To address this issue, 50 male and female adolescents of varied sexual orientations participated in focus groups and interviews. Two types of sexual attraction-one a physiologic reaction and the other a cognitive response-were central to adolescent sexual orientation. Participants did not perceive sexual behavior and self-identification as necessarily relevant. Preliminary items to measure sexual attraction were developed based on these adolescents' perceptions.

Objective: Microtubule-associated protein 2 (MAP-2), a cellular protein restricted to neurons, is important in the control of cytoskeletal integrity and other neuronal functions. We undertook this study to examine the presence of autoantibodies to MAP-2 in neuropsychiatric systemic lupus erythematosus (NPSLE)., Methods: Sera from 100 patients with SLE, 74 patients with other neurologic disorders and injuries (including cerebrovascular accidents, brain trauma, brain tumors, and demyelinating disorders), and 60 normal controls were examined both by enzyme immunoassays and by Western immunoblotting for autoantibodies to MAP-2. Sera designated positive for antibodies to MAP-2 were required to be positive in both assays., Results: Seventeen percent of SLE patients had autoantibodies to MAP-2, in contrast to 4% of neurologic injury/disease control patients (P = 0.028) and 1.7% of normal controls. In SLE, anti-MAP-2 positivity in both assays was associated with neuropsychiatric symptoms in 76.5% of patients, whereas the absence of anti-MAP-2 was associated with neuropsychiatric symptoms in 19.7% of patients (P = 0.0002). The neuropsychiatric symptoms in the former group included psychosis, seizure, neuropathy, and cerebritis., Conclusion: Autoantibodies to MAP-2, a neuron-restricted cytoskeletal protein, appear to be another immune marker for NPSLE.

Background: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria., Methods: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and inter-group differences were evaluated with logistic regression models for correlated data., Results: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05)., Conclusion: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis.

For nearly 50 years David Yphantis has helped advance analytical ultracentrifugation, promoted rigor in the thermodynamic analysis of biochemical data and encouraged students and colleagues to look for the deepest possible understanding of science. This article, written by five of Dave's students, presents some of the impressions he has made over the years.

Background: A NAT was developed (Procleix multiplex, Chiron Corporation) to simultaneously detect HIV-1 and HCV RNA with multiplex transcription-mediated amplification (mTMA) on pooled or single donations. HIV-1 and/or HCV RNA discriminatory probes confirm infection and discriminate the virus type. When a multiplex reactive sample does not react in discriminatory assays, the result is considered nondiscriminated reactive (NDR) and the donor status is uncertain. This study was designed to determine the clinical significance of NDR results., Study Design and Methods: Three years of donor NAT and serology results were reviewed to determine HCV and HIV-1 infection rates as well as NDR events. Index NDR and seronegative donations were retested by mTMA and serology. Follow-up samples were tested by serology, mTMA, and PCR (selected samples)., Results: From April 1999 through April 2002, 5.1 million donations were screened with Procleix HIV-1 and HCV mTMA. The observed NDR rate declined from 0.014 percent (1 in 7242) to 0.0053 percent (1 in 18,795). None of the 462 donors with index NDR donations and additional NAT and serology data (from 724 donation and follow-up samples) were found infected., Conclusion: In most NDRs, the original mTMA reactivity is not reproducible and likely related to technical errors (mTMA cross-contamination). The retest and clinical follow-up data, combined with published evidence that the two discriminatory assays have the same sensitivity as multiplex HIV-1 and HCV, support the recommendation that donors with an NDR result for whom the multiplex reactivity cannot be reproduced should either not be notified or be deferred or should be counseled that they are not infected and expeditiously reinstated.

The purpose of this study was to provide data addressing Diamond's (this issue) 4 problem areas in sexual orientation research by comparing gay, bisexual, and questioning male youth who report attempting suicide with those who do not. Secondary analyses were conducted with 2 datasets, 1 with a gay support group (n = 51) and the other with online youth (n = 681). Reported suicide attempts ranged from 39% among support-group youth, to 25% among Internet gay support group youth, to 9% among Internet non-support group youth. Sexual orientation, behavior, and identity did not predict suicidal attempt status, but suicide attempters experienced higher levels of both generic life stressors (low self-esteem, substance use, victimization) and gay-related stressors, particularly those directly related to visible (femininity) and behavioral (gay sex) aspects of their sexual identity. Support-group attendance was related to higher levels of suicidality and life stressors, as well as certain resiliency factors. Results suggest that there exists a minority of sexual-minority youth who are at risk but that it would be inappropriate to characterize the entire population as such.

Three-dimensional (3D) trapezium models from Homo sapiens, Gorilla gorilla, Pan troglodytes, Australopithecus afarensis (A.L.333-80), and Homo habilis (O.H.7-NNQ) were acquired through laser digitizing. Least-square planes were generated for each articular surface, and the angles between the planes were compared. Each extant species displays an overall pattern that distinguishes it from the others. The observed angles in G. gorilla and P. troglodytes are more similar to one other than either is to H. sapiens. Our results, obtained from using new 3D modeling and analytical tools, raise interesting questions about the functional capabilities of the fossil trapezia. Multivariate statistical analyses indicate that A.L.333-80 is morphologically more similar to that of modern humans, whereas the O.H.7 trapezium is more similar to that of the gorilla. Significant differences between A.L.333-80 and the extant species occur, but some similarities to humans suggest the ability to form the distinctively human forceful pad-to-side and three-jaw chuck grips. Some key morphological differences from humans highlighted and quantified by our research suggest limitations in the functional capabilities of the O.H.7 trapezium, particularly in those that facilitate pronation at the base of the second metacarpal. If the O.H.7 trapezium represents part of the hand responsible for manufacturing and using the stone tools found at Olduvai, our results suggest that the hand manipulated the stones in a way for which we have no modern analog. Alternative considerations are that the O.H.7 trapezium is not representative of other trapezia from its species (i.e., N=1), or that it represents another primate or hominid species., (Copyright 2003 Wiley-Liss, Inc.)

The decision whether to disclose same-sex attractions to parents was explored through in-depth interviews with 164 young women and men. Participants were more likely to disclose to mothers than fathers, usually around age 19 years and in a face-to-face encounter. Mothers were told before fathers, largely because mothers asked or because youth wanted to share their life with them; fathers were told by someone other than their child or by the youth because it was time. The reason participants did not disclose to mothers was because it was not the right developmental time; the reason they did not disclose to fathers was because they were not close to them. Sons, more than daughters, feared the negative reactions of parents, who generally reacted in the same manner--supportive or slightly negative. Relationships with parents since disclosure generally had not changed or had improved. Sex of parent mattered more than sex of child on most domains.

Frank Livingstone played a central role in defining the population genetics of the sickle cell mutation at position 6 of the human beta globin gene, the most famous amino acid substitution in evolutionary biology. Its discovery occurred at a time when traditional, 19th-century principles of natural selection were being joined with the newly discovered mechanics of DNA structure and protein synthesis to produce Neo-Darwinian theory. When combined with the epidemiology of malaria in Africa, differential mortality for both homozygotes, and the resulting advantage of the heterozygote, sickle cell became the classic balanced polymorphism. Human HLA-A has 237 molecular alleles. The histocompatibility system has as its primary function the presentation of peptides to T-cell receptors and plays an essential role in the immune system. Nearly all of the alleles are codominant and fully functional. Despite almost 30 years of disease-association studies with HLA-A, no convincing evidence has been found for differential fertility or mortality at this locus. Yet the dogma in the histocompatibility field is that this extensive human polymorphism is maintained by "balancing selection." Explaining HLA-A polymorphism is what one might call the sickle-cell-effect. This one mutation, coming as it did at the historical convergence of Darwinian theory and modern genetics, and carrying with it the strong relationship between mutation, disease, and allele frequency, has conditioned our discussion of human genetic variation and population genetics. Has the strength of this early idea made evolutionary biologists uncritical of systems like HLA-A and retarded the search for new mechanisms of molecular evolution? Is it now time to move away from a focus on mutation and polymorphism in evolutionary genetics and toward a systems theory that would explain the origin and evolution of hemoglobin and HLA-A and the biochemical pathways that surround them?

Protective antigen (PA) is a component of the Bacillus anthracis lethal and edema toxins and the basis of the current anthrax vaccine. In its heptameric form, PA targets host cells and internalizes the enzymatically active components of the toxins, namely lethal and edema factors. PA and other toxin components are secreted from B. anthracis using the Sec-dependent secretion pathway. This requires them to be translocated across the cytoplasmic membrane in an unfolded state and then to be folded into their native configurations on the trans side of the membrane, prior to their release from the environment of the cell wall. In this study we show that recombinant PA (rPA) requires the extracellular chaperone PrsA for efficient folding when produced in the heterologous host, B. subtilis; increasing the concentration of PrsA leads to an increase in rPA production. To determine the likelihood of PrsA being required for PA production in its native host, we have analyzed the B. anthracis genome sequence for the presence of genes encoding homologues of B. subtilis PrsA. We identified three putative B. anthracis PrsA proteins (PrsAA, PrsAB, and PrsAC) that are able to complement the activity of B. subtilis PrsA with respect to cell viability and rPA secretion, as well as that of AmyQ, a protein previously shown to be PrsA-dependent.

Background: Evaluation of high-risk mammograms represents an enormous clinical challenge. Functional breast imaging coupled with mammography (positron emission mammography [PEM]) could improve imaging of such lesions. A prospective study was performed using PEM in women scheduled for stereotactic breast biopsy., Methods: Patients were recruited from the surgical clinic. Patients were injected with 10 mCi of 2-[18F] fluorodeoxyglucose. One hour later, patients were positioned on the stereotactic biopsy table, imaged with a PEM scanner, and a stereotactic biopsy was performed. Imaging was reviewed and compared with pathologic results., Results: There were 18 lesions in 16 patients. PEM images were analyzed by drawing a region of interest at the biopsy site and comparing the count density in the region of interest with the background. A lesion-to-background ratio >2.5 appeared to be a robust indicator of malignancy and yielded a sensitivity of 86%, specificity of 91%, and overall diagnostic accuracy of 89%. No adverse events were associated with the PEM imaging., Conclusions: The data show that PEM is safe, feasible, and has an encouraging accuracy rate in this initial experience. Lesion-to-background ratios >2.5 were found to be a useful threshold value for identifying positive (malignant) results. This study supports the further development of PEM.

Background: Our research group has recently reported that exogenously applied histatins can inhibit plaque accumulation and gingival inflammation in a preclinical canine model (Paquette et al. 1997)., Objectives: The aims of the present double-blinded, randomized, controlled clinical trial were to evaluate the safety and toxicity of three histatin (P-113) concentrations in gel formulations, and to assess potential clinical benefit on the development of gingivitis (partial mouth design)., Material and Methods: One hundred and six healthy subjects were recruited and brought to optimal gingival health (GI < 0.5) prior to treatment initiation. At baseline, eligible subjects were randomized for one of the following treatments: (1) placebo; (2) 0.0625% P-113; (3) 0.125% P-113; and (4) 0.375% P-113. Patients self-applied gels twice daily for 29 days to the maxillary right quadrant with the use of customized stents. In addition, patients deferred all oral hygiene procedures within this quadrant for the duration of the treatment period. Safety was assessed in terms of physical and oral examinations, clinical laboratory testing and recording of adverse events. Clinical indices were measured weekly and included gingival index (GI), plaque index (PI) and %BOP., Results: All study formulations were well tolerated by patients, and no differences in adverse event occurrences were noted among treatment groups, including taste alteration or staining. For the intent-to-treat population, significantly smaller %BOP changes were noted in subjects treated with 0.0625, 0.125 and 0.375% P-113 gels (17.4, 18.18 and 17.9%, respectively) versus placebo (28.0%) (p < 0.05) at day 29. When groups were compared in terms of per cent responders (change in %BOP < 15 or < 20%), P-113 treatment groups exhibited a higher frequency of response, especially for the 0.0625 and 0.125% P-113 formulations (p < 0.05). Although no statistically significant intergroup differences were noted for changes in GI or PI among all subjects (intent-to-treat population), significantly smaller changes in PI at day 22 were observed among compliant individuals (defined as subjects using > 60% of the target gel mass) administering P-113 gels as compared with compliant placebo subjects (p < 0.05)., Conclusions: These data indicate safety and tolerance of P-113 gels for topical oral use in human subjects. These data also suggest that P-113 gels administered twice daily may reduce experimental gingivitis as measured with bleeding on probing in humans.

Growth and shortening of microtubules in the course of their polymerization and depolymerization have previously been observed to occur at variable rates. To gain insight into the meaning of this prominent variability, we studied the way in which its magnitude depends on the growth rate of experimentally observed and computer-simulated microtubules. The dynamic properties of plus-ended microtubules nucleated by pieces of Chlamydomonas flagellar axonemes were observed in real time by video-enhanced differential interference contrast light microscopy at differing tubulin concentrations. By means of a Monte Carlo algorithm, populations of microtubules were simulated that had similar growth and dynamic properties to the experimentally observed microtubules. By comparison of the experimentally observed and computer-simulated populations of microtubules, we found that 1) individual microtubules displayed an intrinsic variability that did not change as the rate of growth for a population increased, and 2) the variability was approximately fivefold greater than predicted by a simple model of subunit addition and loss. The model used to simulate microtubule growth has no provision for incorporation of lattice defects of any type, nor sophisticated geometry of the growing end. Thus, these as well as uncontrolled experimental variables were eliminated as causes for the prominent variability.

Throughout the 20th century, investigators and clinicians sought to discover the causes and trace the natural history of periodontal disease. Noteworthy progress has been made on several fronts. It was once believed that oral hygiene and age accounted predominantly for variances in the prevalence and severity of periodontal disease; now, a number of innate, acquired, and environmental risk factors have been identified. Light has been shed on the roles in periodontal disease pathogenesis of both specific bacteria and bacterial complexes and host immunoinflammatory responses. Insight into periodontal wound healing has fostered promising approaches to promoting regeneration of damaged periodontal structures. Finally, although theories of "focal infection" as a primary cause of systemic disease have been discredited, recent studies have confirmed the existence of an intimate connection between oral and systemic health. The progress made in understanding the nature of periodontal disease has been complemented by equally noteworthy therapeutic advances. The coupling of surgical and medical approaches to treatment ushers in a new era in the management of periodontal disease.

Apoptosis is deregulated in active systemic lupus erythematosus and Fas is overexpressed by T cells, although the role of its soluble form (sFas) is unclear. We have explored both the biological significance and structure of sFas in relation to the disease activity. Serum levels of both sFas and sFas-L were correlated with T cell apoptosis in 26 systemic lupus eythematosus patients along with measurement of poly (ADP) ribose polymerase and CK18. In addition, both proliferative rate and change of ploidy were measured in CD3+ cells after treatment with sFas. Both sFas and sFas-L correlated with apoptosis in patients with active systemic lupus eythematosus. Incubation with sFas greatly suppressed proliferation of CD3+ cells from inactive patients and healthy donors, whereas immunoprecipitation revealed both the 48-kDa full-length Fas and the 26-kDa splicing variant in sera from active patients. We postulate that sFas is released to exert a pro-apoptogen effect. It seems possible that the apoptosis program itself includes the shedding/secretion of different forms of Fas to spread a death signal.

A 61-year-old woman with a history of photosensitive dermatitis and recurrent mouth ulcers presented with progressive weakness typical of amyotrophic lateral sclerosis (ALS), and subsequently underwent extensive neurologic and rheumatologic testing. We investigated whether ALS-like motor neuron disease associated with a positive antinuclear antibody (ANA) is really ALS or rather neuropsychiatric systemic lupus erythematosus (NPSLE). On neurologic evaluation, she had prominent bulbar involvement with dysarthria and dysphagia associated with profound lingual fasciculations and a denervating pattern on electromyogram. MRI showed no evidence of cerebral ischemia. Laboratory studies revealed a positive ANA (1:2560 titer), positive antiphospholipid antibodies (GPL and MPL), circulating lupus anticoagulant, and depressed C3 and C4. Repeat MRI studies at 4 and 11 mo revealed an evolving infarct in the paramedian pons consistent with the presence of NPSLE. Therapy was initiated with corticosteroids and intravenous cyclophosphamide, and the neurologic condition did not improve, but also did not progress inexorably as would be expected with ALS. NPSLE, presumably through the mechanism of ischemic vasculopathy, may present as motor neuron disease clinically indistinguishable from ALS.

Two questions were addressed regarding suicide attempts among sexual-minority youths: Who should be classified as a sexual minority, and what constitutes a suicide attempt? Results from 2 studies indicated that sexual-minority youths, broadly defined in terms of sexual orientation and recruitment venue, were slightly more likely than heterosexual youths to report a suicide attempt. To afford a more accurate assessment of suicide attempts, a detailed measure distinguished true from false attempts. This method eliminated over half of suicide attempt reports among sexual minorities because they were false attempts-ideation rather than a concrete act to end life. Furthermore, many true attempts were not life threatening, suggesting that the reports were attempts to communicate the hardships of lives or to identify with a gay community.

Background: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline., Methods: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months., Results: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups., Conclusions: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Amphipathic variable-region heavy chain 11-mer peptides from monoclonal human IgM antiproteinase-3 antibodies were studied for peripheral blood lymphocyte stimulation in 21 patients with Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA), connective tissue disease controls and normal control subjects. Positive T-cell activation was observed in most experiments with WG patients' lymphocytes using amphipathic VH-region peptides from four different human monoclonal anti-PR3 antibodies. Control peptides of the same length but without amphipathic characteristics along with other amphipathic peptides not derived from monoclonal anti-PR3 sequence were employed as controls. No significant lymphocyte stimulation was observed with normal controls, but positive stimulation with amphipathic VH peptides was also recorded in other connective tissue disease controls mainly patients with rheumatoid arthritis. Amphipathic peptides not derived from anti-PR3 sequence did not stimulate WG lymphocytes. Our findings indicate that lymphocyte reactivity as an element of cell-mediated immunity may be activated by amphipathic VH-region amino acid sequences of autoantibodies which are themselves associated with diseases such as WG.

A circular dichroism (CD) detector in series with a UV detector was used with reversed-phase gradient HPLC to do the chiral analysis of unresolved enantiomers of a single stereoisomer drug substance in extracts of clinical plasma samples. The CD/UV peak area ratio of the unresolved enantiomers in the plasma extracts was calculated and compared with pure drug substance standards to show that there was no racemization of the chiral center during pharmacokinetic studies. The CD detector can be used only with chiral compounds with a UV chromophore and the limit of detection was approximately 5 ng with the drug substance and chromatographic conditions used in this study.