Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD.

BACKGROUND AND OBJECTIVE: The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. METHODS: All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. RESULTS: Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. CONCLUSION: The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

Validation of a shortened MR imaging protocol for pediatric spinal pathology.

OBJECTIVE: Conventional pediatric spine MRI protocols have multiple sequences resulting in long acquisition times. Sedation is consequently required. This study evaluates the diagnostic capability of a limited MRI spine protocol for selected common pediatric indications. METHODS: Spine MRIs at CHEO between 2017 and 2020 were reviewed across pediatric patients younger than four years old. Two blinded neuroradiologists reviewed limited scan sequences, and results were independently compared to previously reported findings from the complete imaging series. T2 sagittal sequences from the craniocervical junction to sacrum and T1 axial sequence of the lumbar spine constitute the short protocol, with the outcomes of interest being cerebellar ectopia, syrinx, level of conus, filum < 2 mm, fatty filum, and spinal dysraphism. RESULTS: A total of 105 studies were evaluated in 54 male and 51 female patients (mean age 19.2 months). The average combined scan time of the limited sequences was 15 min compared to 35 min for conventional protocols (delta = 20 min). The average percent agreement between full and limited sequences was > 95% in all but identifying a filum < 2 mm, where the percent agreement was 87%. Using limited MR sequences had high sensitivity (> 0.91) and specificity (> 0.99) for the detection of cerebellar ectopia, syrinx, fatty filum, and spinal dysraphism. CONCLUSION: This study demonstrates that selected spinal imaging sequences allow for consistent and accurate diagnosis of specific clinical conditions. A limited spine imaging protocol has potential as a screening test to reduce the need for full-sequence MRI scans. Further work is needed to determine utility of selected imaging for other clinical indications.

Electrocatalytic CO2 Reduction by [Re(CO)3Cl(3-(pyridin-2-yl)-5-phenyl-1,2,4-triazole)] and [Re(CO)3Cl(3-(2-pyridyl)-1,2,4-triazole)].

The exploration of novel electrocatalysts for CO2 reduction is necessary to overcome global warming and the depletion of fossil fuels. In the current study, the electrocatalytic CO2 reduction of [Re(CO)3Cl(N-N)], where N-N represents 3-(2-pyridyl)-1,2,4-triazole (Hpy), 3-(pyridin-2-yl)-5-phenyl-l,2,4-triazole (Hph), and 2,2'-bipyridine-4,4' dicarboxylic acidic (bpy-COOH) ligands, was investigated. In CO2-saturated electrolytes, cyclic voltammograms showed an enhancement of the current at the second reduction wave for all complexes. In the presence of triethanolamine (TEOA), the currents of Re(Hpy), Re(Hph), and Re(bpy-COOH) enhanced significantly by approximately 4-, 2-, and 5-fold at peak potentials of -1.60, -150, and -1.69 VAg/Ag+, respectively (in comparison to without TEOA). The reduction potential of Re(Hph) was less negative than those of Re(Hpy) and Re(COOH), which was suggested to cause its least efficiency for CO2 reduction. Chronoamperometry measurements showed the stability of the cathodic current at the second reduction wave for at least 300 s, and Re(COOH) was the most stable in the CO2-catalyzed reduction. The appearance and disappearance of the absorption band in the UV/vis spectra indicated the reaction of the catalyst with molecular CO2 and its conversion to new species, which were proposed to be Re-DMF + and Re-TEOA and were supposed to react with CO2 molecules. The CO2 molecules were claimed to be captured and inserted into the oxygen bond of Re-TEOA, resulting in the enhancement of the CO2 reduction efficiency. The results indicate a new way of using these complexes in electrocatalytic CO2 reduction.

Anodal Transcranial Direct Current Stimulation Enhances Retention of Visuomotor Stepping Skills in Healthy Adults.

Transcranial direct current stimulation (tDCS) paired with exercise training can enhance learning and retention of hand tasks; however, there have been few investigations of the effects of tDCS on leg skill improvements. The purpose of this study was to investigate whether tDCS paired with visuomotor step training can promote skill learning and retention. We hypothesized that pairing step training with anodal tDCS would improve skill learning and retention, evidenced by decreased step reaction times (RTs), both immediately (online skill gains) and 30 min after training (offline skill gains). Twenty healthy adults were randomly assigned to one of two groups, in which 20-min anodal or sham tDCS was applied to the lower limb motor cortex and paired with visuomotor step training. Step RTs were determined across three time points: (1) before brain stimulation (baseline); (2) immediately after brain stimulation (P0); and (3) 30 min after brain stimulation (P3). A continuous decline in RT was observed in the anodal tDCS group at both P0 and P3, with a significant decrease in RT at P3; whereas there were no improvements in RT at P0 and P3 in the sham group. These findings do not support our hypothesis that anodal tDCS enhances online learning, as RT was not decreased significantly immediately after stimulation. Nevertheless, the results indicate that anodal tDCS enhances offline learning, as RT was significantly decreased 30 min after stimulation, likely because of tDCS-induced neural modulation of cortical and subcortical excitability, synaptic efficacy, and spinal neuronal activity.

[Sentinel surveillance for viral hepatitis C in China, 2016-2017].

Objective: To understand the prevalence of hepatitis C virus (HCV) infection in 5 populations in China during 2016-2017 and provide evidence for the estimation of prevalence trend of hepatitis C and evaluation on the prevention and control effect. Methods: A total of 87 national sentinel surveillance sites for hepatitis C were set up in 31 provinces (autonomous regions and municipalities) of China to obtain the information about HCV infection prevalence in 5 populations, including volunteer blood donors, people receiving physical examination, patients receiving invasive diagnosis and treatment, patients receiving hemodialysis, and clients visiting family planning outpatient clinics. From April to June, 2016 and 2017, cross-sectional surveys were repeatedly conducted in the 5 populations and blood samples were collected from them for HCV antibody detection. Results: In 2016, 86 sentinel sites completed the surveillance (one sentinel site was not investigated), and 115 841 persons were surveyed. The overall HCV positive rate was 0.38% (442/115 841, 95%CI: 0.23%-0.53%). In 2017, all the 87 sentinel sites completed the surveillance, and 120 486 persons were surveyed. The overall HCV positive rate was 0.37% (449/120 486, 95%CI: 0.23%-0.52%). In 2016 and 2017, the anti-HCV positive rates were 4.46% (223/5 005, 95%CI: 2.18%-6.73%) and 4.39% (216/4 919, 95%CI: 2.29%-6.50%) respectively in hemodialysis patients, 0.85% (44/5 200, 95%CI: 0.27%-1.42%) and 0.70% (36/5 150, 95%CI: 0.15%-1.24%) respectively in patients receiving invasive diagnosis and treatment and remained to be ≤0.25% in volunteer blood donors, people receiving physical examination and clients visiting family planning outpatient clinics. Results for the comparison of the anti-HCV positive rates in the 5 populations indicated that the differences were significant (F=23.091, P<0.001 in 2016 and F=20.181, P<0.001 in 2017). Conclusions: Data from the sentinel surveillance of HCV infection on prevalence in China showed that the anti-HCV positive rates varied in the 5 populations during 2016-2017. The anti-HCV positive rate appeared the highest in the hemodialysis patients, followed by that in the patients receiving invasive diagnosis and treatment, and the prevalence of HCV infection in other 3 populations were at low levels.

A Low-Cost Imaging Method for the Temporal and Spatial Colorimetric Detection of Free Amines on Maize Root Surfaces.

Plant root exudates are important mediators in the interactions that occur between plants and microorganisms in the soil, yet much remains to be learned about spatial and temporal variation in their production. This work outlines a method utilizing a novel colorimetric paper to detect spatial and temporal changes in the production of nitrogen-containing compounds on the root surface. While existing methods have made it possible to conduct detailed analysis of root exudate composition, relatively less is known about where in the root system exudates are produced and how this localization changes as the root grows. Furthermore, there is much to learn about how exudate localization and composition varies in response to stress. Root exudates are chemically diverse secretions composed of organic acids, amino acids, proteins, sugars, and other metabolites. The sensor utilized for the method, ninhydrin, is a colorless substance in solution that reacts with free amino groups to form a purple dye. A detection paper was developed by formulating ninhydrin into a print solution that was uniformly deposited onto paper with a commercial ink jet printer. This "ninhydrin paper" was used to analyze the chemical makeup of root surfaces from maize seedlings grown vertically on germination paper. Through contact between the ninhydrin paper and seedling root surfaces, combined with images of both the seedlings and dried ninhydrin papers captured using a standard flatbed scanner, nitrogen-containing substances on the root surface can be localized and concentration of signal estimated for over 2 weeks of development. The method was found to be non-inhibiting to plant growth over the analysis period although damage to root hairs was observed. The method is sensitive in the detection of free amines at concentrations as little as 140 µM. Furthermore, ninhydrin paper is stable, showing consistent color changes up to 2 weeks after printing. This relatively simple, low-cost method could contribute to a better understanding of root exudates and mechanisms used by plants to interact with the complex soil environment during growth and development.

Skeletal muscle growth dynamics and the influence of first-feeding diet in Atlantic cod larvae (Gadus morhua L.).

Dynamics between hypertrophy (increase in cell size) and hyperplasia (increase in cell numbers) of white and red muscle in relation to body size [standard length (SL)], and the influence of the first-feeding diets on muscle growth were investigated in Atlantic cod larvae (Gadus morhua). Cod larvae were fed copepod nauplii or rotifers of different nutritional qualities from 4 to 29 days post hatching (dph), Artemia nauplii from 20 to 40 dph and a formulated diet from 36 to 60 dph. The short period of feeding with cultivated copepod nauplii had a positive effect on both muscle hyperplasia and hypertrophy after the copepod/rotifer phase (19 dph), and a positive long term effect on muscle hypertrophy (60 dph). The different nutritional qualities of rotifers did not significantly affect muscle growth. We suggest here a model of the dynamics between hyperplasia and hypertrophy of red and white muscle fibre cells in relation to cod SL (4 to 30 mm), where the different red and white muscle growth phases clearly coincided with different metamorphosis stages in cod larvae. These shifts could be included as biomarkers for the different stages of development during metamorphosis. The main dietary muscle effect was that hypertrophic growth of red muscle fibres was stronger in cod larvae that were fed copepods than in larvae that were fed rotifers, both in relation to larval age and size. Red muscle fibres are directly involved in larval locomotory performance, but may also play an important role in the larval myogenesis. This can have a long term effect on growth potential and fish performance.

Molecular and morphological variation of Paragonimus westermani in Vietnam with records of new second intermediate crab hosts and a new locality in a northern province.

Paragonimus westermani is one of the most medically important lung flukes and is widely distributed in Asia. It exhibits considerable variation in morphological, genetic and biological features. In central provinces of Vietnam, a high prevalence of metacercariae of this species has been reported from the crab intermediate host, Vietopotamon aluoiense. In this study, we detected P. westermani metacercariae in two additional crab hosts, Donopotamon haii in Quang Tri Province, central Vietnam and Indochinamon tannanti in Yen Bai Province in the north. The latter is a new locality for P. westermani in a northern region of Vietnam where P. heterotremus is the only species currently known to cause human paragonimiasis. Paragonimus westermani metacercariae found in Vietnam showed considerable morphological variation but slight genetic variation based on DNA sequences from the nuclear ribosomal ITS2 region and the mitochondrial 16S gene. Co-infection of the same individual crabs with P. westermani and P. heterotremus and/or some other Paragonimus species was found frequently, suggesting potential for co-infection in humans. The findings of the present study emphasize the need for highly specific molecular and immunodiagnostic methods to differentially diagnose between P. westermani and P. heterotremus infections.

Using Mixed Methods to Examine the Role of Veterans' Illness Perceptions on Depression Treatment Utilization and HEDIS Concordance.

BACKGROUND: Although depression screening occurs annually in the Department of Veterans Affairs (VA) primary care, many veterans may not be receiving guideline-concordant depression treatment. OBJECTIVES: To determine whether veterans' illness perceptions of depression may be serving as barriers to guideline-concordant treatment. RESEARCH DESIGN: We used a prospective, observational design involving a mailed questionnaire and chart review data collection to assess depression treatment utilization and concordance with Healthcare Effectiveness Data and Information Set guidelines adopted by the VA. The Self-Regulation Model of Illness Behavior guided the study. SUBJECTS: Veterans who screened positive for a new episode of depression at 3 VA primary care clinics in the US northeast. MEASURES: The Illness Perceptions Questionnaire-Revised, measuring patients' perceptions of their symptoms, cause, timeline, consequences, cure or controllability, and coherence of depression and its symptoms, was our primary measure to calculate veterans' illness perceptions. Treatment utilization was assessed 3 months after the positive depression screen through chart review. Healthcare Effectiveness Data and Information Set (HEDIS) guideline-concordant treatment was determined according to a checklist created for the study. RESULTS: A total of 839 veterans screened positive for a new episode of depression from May 2009-June 2011; 275 (32.8%) completed the survey. Ninety-two (33.9%) received HEDIS guideline-concordant depression treatment. Veterans' illness perceptions of their symptoms, cause, timeline, and controllability of depression predicted receiving guideline-concordant treatment. CONCLUSIONS: Many veterans are not receiving guideline-concordant treatment for depression. HEDIS guideline measures may not be assessing all aspects of quality depression care. Conversations about veterans' illness perceptions and their specific needs are encouraged to ensure that appropriate treatment is achieved.

Aum Shinrikyo's Chemical and Biological Weapons: More Than Sarin.

The radical religious group Aum Shinrikyo was founded in Japan in the 1980s and grew rapidly in the 1990s. Aum members perpetrated a mass murder in Matsumoto City in 1994, where they used sarin as a chemical weapon to poison approximately 500 civilians. On March 20, 1995, Aum deployed sarin in an even larger terrorist attack on the Tokyo Subway System, which poisoned some 6,000 people. After the Tokyo Subway attack, the Japanese Police arrested the sect's senior members. From 2005 through 2011, 13 of these senior members were sentenced to death. In this article, aspects of Aum's chemical and biological terrorism are reviewed. Sarin production efforts by the sect are described, including how the degradation product of sarin in soil, methylphosphonic acid, enabled the detection of sarin production sites. Also, Aum's chemical-warfare agents other than sarin are described, as are its biological weapons. The author was permitted by the Japanese government to interview Dr. Tomomasa Nakagawa, one of the senior members of Aum Shinrikyo. From Dr. Nakagawa the author obtained valuable inside information about Aum's chemical and biological weapons programs.

Hepatitis C and HIV prevalence using oral mucosal transudate, and reported drug use and sexual behaviours of youth in custody in British Columbia.

BACKGROUND: Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population was assessed in British Columbia (BC) in 1994 but hepatitis C virus (HCV) prevalence has never been measured. We sought to determine: 1) the performance of the OraSure, a non-invasive device for oral mucosal transudate (OMT) specimen collection, to detect HCV and HIV antibodies; 2) the prevalence of HCV and HIV among youth in custody; and 3) the factors associated with intravenous drug use and sex for trade. METHODS: OraSure was validated in 110 adults with known HIV and HCV sero-status. Nurses administered an anonymous survey and collected OMT samples from youth aged 14-19 years in BC youth custody centres. RESULTS: Antibody detection in OMT had 96.4% sensitivity for HIV and 94.6% for HCV. 417 youth were enrolled; 22% were female; 48% reported Aboriginal ethnicity. Although 98.3% reported ever using drugs, <8% reported injection drug use (IDU). IDU was independently associated with age of first sexual intercourse (inverse association) and sex for trade (sex in exchange for money, drugs, food or shelter) (OR 4.28; 95% CI: 1.56-11.75). Females were >9 times more likely to report sex for trade. Five Aboriginal youth were identified with HCV; prevalence estimate 1.2% (95% CI: 0.53-2.77%); 3 reported injecting drugs, the other 2 reported using cocaine/crack and sharing non-injection drug paraphernalia. Two youth were identified with HIV, prevalence estimate 0.48% (95% CI: 0.14%-1.72%). CONCLUSION: IDU, HCV and HIV prevalence remain low. Interventions are needed to prevent transition to IDU and further opportunities for prevention and harm reduction should be explored while the youth are in custody.

Iris melanoma in 12-year-old boy.

A 12-year-old boy presented with an incidental finding of an iris lesion after blunt injury. Ocular examination revealed a large atypical brown vascular nodule in the nasal iris, extending to the pupillary margin. There were smaller scattered nodules scattered within the iris and anterior chamber. Ultrasound biomicroscopy examination revealed no tumour behind the iris. Fundal examination findings were normal. Sector iridectomy revealed mixed spindle and epitheliod melanoma. The eye was enucleated. Histopathologic examination confirmed malignant melanoma confined to the iridocorneal angle, iris, ciliary body and inner layer of the anterior sclera. Iris melanomas are very rare in the prepubertal age group.

Association of a major protein antigen of Mycoplasma arthritidis with virulence.

Mycoplasma arthritidis causes acute polyarthritis in rats and chronic proliferative arthritis in mice. M. arthritidis-induced arthritis serves as a model for arthritis caused by infectious agents and as a model for examining the role of the superantigen MAM (M. arthritidis T-cell mitogen) in the development of autoimmunity. M. arthritidis strain 158-1 is a spontaneous mutant of strain 158 that has a drastic reduction in virulence. We show that the mutant is missing a major antigen of 47 kDa (P47) and has acquired a protein of 67 kDa (P67). P47 and P67 partitioned into the detergent phase by extraction with Triton X-114. Coomassie blue staining of sodium dodecyl sulfate-polyacrylamide gels show that P67 is produced in abundance. Analysis of gel-purified P67 by mass spectrometry led to its identification as a lipoprotein (the open reading frame [ORF] 619 gene product) predicted from the genome sequence of M. arthritidis. PCR analysis of genomic DNA from 158 and 158-1 indicates that P47 and P67 are encoded by the same ORF 619 gene and differ only in the number of repeats in a tandem repeat region. By two-dimensional polyacrylamide gel analysis, no protein differences were detectable between 158 and 158-1 other than P47 and P67. Collectively, the data suggest that the tandem repeat region of P47 and P67 influences disease outcome.

Purification, sequencing, and phylogenetic analyses of novel Lys-49 phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.

Basic phospholipase A(2) homologs with Lys49 substitution at the essential Ca(2+)-binding site are present in the venom of pit vipers under many genera. However, they have not been found in rattlesnake venoms before. We have now screened for this protein in the venom of rattlesnakes and other less studied pit vipers. By gel filtration chromatography and RP-HPLC, Lys49-phospholipase-like proteins were purified from the venoms of two rattlers, Crotalus atrox and Crotalus m. molossus, and five nonrattlers, Porthidium nummifer, Porthidium godmani, Bothriechis schlegelii, Trimeresurus puniceus, and Trimeresurus albolabris. Their N-terminal amino acid sequences were shown to be characteristic for this phospholipase subfamily. The purified basic proteins from rattlesnakes caused myonecrosis and edema in experimental animals. We have also cloned the cDNAs and solved the complete sequences of four novel Lys49-phospholipases from the venom glands of C. atrox, P. godmani, B. schlegelii, and Deinagkistrodon acutus (hundred-pace). Phylogenetic analyses based on the amino acid sequences of 28 Lys49-phospholipases separate the pitviper of the New World from those of the Old World, and the arboreal Asiatic species from the terrestrial Asiatic species. The implications of the phylogeny tree to the systematics of pit vipers, and structure-function relationship of the Lys49-phospholipases are discussed.

Functional analysis of the transcriptional activity of the mouse phospholipid transfer protein gene.

Phospholipid transfer protein (PLTP) plays an important role in the metabolism of plasma high density lipoprotein. The mouse gene encoding PLTP and its promoter region has been cloned in our laboratory. The present study was conducted to functionally analyze the transcriptional regulation of the mouse PLTP gene. The results indicated that DNA sequences between -245 and -69 were responsible for the full promoter activity and binding motifs for transcription factor Sp1 and AP-2 within this functional promoter region were synergistically essential for the basal transcription. The transcriptional activity of this gene was significantly increased by chenodeoxycholic acid and fenofibrate, suggesting that transcription factor farnesoid X-activated receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) are likely involved in the transcriptional regulation. DNA sequence analysis suggests that DNA sequences from -407 to -395 and from -393 to -381 are homologous to the recognition motifs of FXR, and those from -859 to -847 and from -309 to -297 are similar to the potential binding motif for PPAR. These findings provide a molecular basis for further investigation of the physiological function and regulation of the PLTP gene in mice.

Normalization of retinal vascular permeability in experimental diabetes with genistein.

PURPOSE: To study the effects of genistein, a tyrosine kinase inhibitor, on retinal vascular permeability in an experimental diabetic rat model. METHODS: Seventy-two rats were equally divided into four groups: (1) nondiabetic control group, (2) diabetic control group, (3) diabetic rats receiving 150 mg genistein/kg food, and (4) diabetic rats receiving 300 mg genistein/kg food. Diabetes was induced by streptozotocin injection in the three diabetic groups. Rats were fed diets with or without genistein and followed for 6 months. Retinal vascular permeability was assessed by measuring radiolabeled sucrose leakage into the retina and by Western blot analysis for total retinal albumin. Retinal phosphotyrosine levels and proliferating cell nuclear antigen (PCNA) were also evaluated by Western blot analysis. RESULTS: Diabetic control rats had markedly increased retinal vascular leakage of radiolabeled sucrose compared with nondiabetic control rats. Diabetic rats receiving oral genistein had significantly less retinal vascular leakage of radiolabeled sucrose than diabetic control rats in a dose-response fashion. Diabetic control rats had increased levels of phosphotyrosine, retinal albumin, and PCNA by Western blot analysis compared with nondiabetic control rats. Rats receiving 300 mg of genistein had decreased retinal albumin by Western blot analysis. Western blot analysis demonstrated a dose-response decrease in retinal phosphotyrosine levels and PCNA in genistein-treated diabetic rats compared with diabetic control rats. CONCLUSIONS: Long-term oral administration of genistein significantly inhibits retinal vascular leakage in experimentally induced diabetic rats. Tyrosine kinase inhibition may be a useful pharmacological approach for the treatment of diabetic-induced retinal vascular leakage.

Glucose regulates the transcription of human genes relevant to HDL metabolism: responsive elements for peroxisome proliferator-activated receptor are involved in the regulation of phospholipid transfer protein.

Phospholipid transfer protein (PLTP) plays an important role in human plasma HDL metabolism. Clinical data have recently indicated that plasma PLTP activity and mass were both higher in diabetic patients concomitant with hyperglycemia. The present study shows that high glucose increases both PLTP mRNA and functional activity in HepG2 cells, due to a significant increase in the promoter activity of human PLTP gene. The glucose-responsive elements are located between -759 and -230 of the PLTP 5'-flanking region, within which two binding motifs (-537 to -524 and -339 to -327) for either peroxisome proliferator-activated receptor or farnesoid X-activated receptor are involved in this glucose-mediated transcriptional regulation. This finding suggests that high glucose upregulates the transcription of human PLTP gene via nuclear hormone receptors. In addition, high glucose increases mRNA levels for several genes that are functionally important in HDL metabolism, including human ATP-binding cassette transporter A1, apolipoprotein A-I, scavenger receptor BI, and hepatic lipase. The functional promoter activities of these genes are enhanced by high glucose in three cell lines tested, indicating that glucose may also regulate these genes at the transcriptional level. Our findings provide a molecular basis for a role of hyperglycemia in altered HDL metabolism.

Variations in the surface proteins and restriction enzyme systems of Mycoplasma pulmonis in the respiratory tract of infected rats.

Restriction and modification (R-M) systems are generally thought to protect bacteria from invasion by foreign DNA. This paper proposes the existence of an alternative role for the phase-variable R-M systems encoded by the hsd loci of Mycoplasma pulmonis. Populations of M. pulmonis cells that arose during growth in different environments were compared with respect to R-M activity and surface antigen production. When M. pulmonis strain X1048 was propagated in laboratory culture medium, > 95% of colony-forming units (cfu) lacked R-M activity and produced the variable surface protein VsaA. Mycoplasmas isolated from the nose of experimentally infected rats also lacked R-M activity and produced VsaA. In contrast, the cell population of mycoplasmas isolated from the lower respiratory tract of the infected rats was more complex. The most dramatic results were obtained for mycoplasmas isolated from the trachea. At 14 days postinfection, 38% of mycoplasma isolates produced a Vsa protein other than VsaA, and 34% of isolates had active restriction systems. These data suggest that differences in selection pressures in animal tissues affect the surface proteins and the R-M activity of the mycoplasmal cell population. We propose that variations in the production of R-M activity and cell surface proteins are important for the survival of the mycoplasma within the host.

Analyses of snake venom for forensic investigation.

Snake venoms are responsible for two reported human deaths as determined by the double diffusion method. Double diffusion is a simple, rapid, and reliable method, but it is rather qualitative and requires a rather large quantity of sample. In order to evaluate venom concentration more quantitatively, the more sensitive ELISA (enzyme linked immunosorbent assay) method was used as an alternative, and the results were compared with that of the double diffusion method.