[Relationship between dispensary treatment and serial examinations].
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Follow-Up Studies↗
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Expression of public idiotypes in patients with Lyme arthritis.
OBJECTIVE: Joints are often affected in Lyme disease and in some instances this may be due to immune autoreactivity. To characterise further the immune response in this disease investigations were carried out to determine the expression of three public idiotypes on serum immunoglobulins in patients with Lyme disease during the development of varying degrees of arthritis. METHODS: The expression of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on monoclonal antibodies to DNA, was determined by an enzyme linked immunosorbent assay (ELISA) in serial blood samples from 12 patients with Lyme disease over a mean period of six years during the development of a variety of arthritic symptoms, and in serum samples from healthy control subjects and control subjects with systemic lupus erythematosus. RESULTS: Expression of serum IgM or IgG public Ids 16/6 and BEG2 was significantly increased in patients with Lyme disease. IgA Id 16/6 expression, in contrast, was significantly increased only during episodes of arthritis and was also related to its severity. IgM and IgG Id 16/6 expression was related to their respective total immunoglobulin concentration and, in the case of IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas similar findings were not apparent with IgA antibodies. This may indicate that the IgA response is related to the pathogenesis of arthritis, especially as total IgA and IgA Id 16/6 levels were found to increase over the duration of disease. Sequential analysis of antibodies also showed restriction in the expression of Id 16/6 as it was never found on all immunoglobulin isotypes at the same time, and Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however, may be associated as seven patients expressed these idiotypes simultaneously. CONCLUSIONS: These data indicate the use of public idiotypes in the immune response against B burgdorferi, which may be restricted in terms of idiotype class and isotype expression, and a possible association between IgA antibodies bearing Id 16/6 with arthritis.
Adult↗
CIBEX: center for information biology gene expression database.
We describe the current status of the gene expression database CIBEX (Center for Information Biology gene EXpression database, http://cibex.nig.ac.jp), with a data retrieval system in compliance with MIAME, a standard that the MGED Society has developed for comparing and data produced in microarray experiments at different laboratories worldwide. CIBEX serves as a public repository for a wide range of high-throughput experimental data in gene expression research, including microarray-based experiments measuring mRNA, serial analysis of gene expression (SAGE tags), and mass spectrometry proteomic data.
Computational Biology↗
Ten quick tips for spatial transcriptomics analysis.
Spatial transcriptomics (ST) enables genome-wide gene expression profiling while retaining spatial context within tissue sections. Since the foundational work by Ståhl et al. in 2016, the field has expanded rapidly, with diverse platforms now spanning sequencing-based (e.g., Visium, Visium HD, Slide-seq, Stereo-seq, and Seq-Scope) and imaging-based (e.g., MERFISH, Xenium, and CosMx SMI) approaches. The breadth of platforms, data structures, and computational tools, however, can be daunting for newcomers. Here, we present ten quick tips spanning the entire ST research workflow: whether ST suits a given biological question, how to select a platform aligned with study objectives, how to understand and process ST data, and which software tools to employ for analysis and visualization. We further discuss interpreting spatial patterns in biological context, integrating complementary modalities such as single-cell RNA sequencing and spatial proteomics, and leveraging public datasets and sharing results. Finally, we highlight current limitations of ST, particularly the challenge of reconstructing three-dimensional tissue architecture from serial tissue sections. This review provides biologists, bioinformaticians, and clinician-scientists with a concise, platform-neutral roadmap for incorporating ST into research, from experimental design to biological discovery.
Spatial Transcriptomics↗
Estimation of serial interval and incubation period of tuberculosis using DNA fingerprinting.
OBJECTIVE: To determine the frequency distributions of serial interval and incubation period of tuberculosis within 4 years of transmission, and to identify correlates of serial intervals and incubation periods. METHODS: DNA fingerprints were obtained for all isolates from all culture-positive patients notified in The Netherlands from 1993 to 1996. Patient information was obtained from the National Tuberculosis Register. Results from contact investigations were provided by public health services. Source cases and secondary cases of tuberculosis were identified, based on 1) identical DNA fingerprints, and 2) epidemiological confirmation of contact. Under-representation of long intervals were corrected for by weighting cases. RESULTS: A total of 69 source-secondary case couples were identified. The geometric mean serial interval was 29.5 weeks (95% confidence interval [CI] 22.8-38.2 weeks) and the geometric mean incubation period 20.8 weeks (95% CI 15.5-27.8 weeks). Serial intervals and incubation periods tended to increase with age (P > 0.05). Three secondary cases with human immunodeficiency virus infection showed very short incubation periods (P > 0.05). CONCLUSION: Using a new methodology, the distribution of incubation periods of tuberculosis gave results consistent with earlier studies.
Adolescent↗
A preliminary transcriptome map of non-small cell lung cancer.
We constructed a genome-wide transcriptome map of non-small cell lung carcinomas based on gene-expression profiles generated by serial analysis of gene expression (SAGE) using primary tumors and bronchial epithelial cells of the lung. Using the human genome working draft and the public databases, 25,135 nonredundant UniGene clusters were mapped onto unambiguous chromosomal positions. Of the 23,056 SAGE tags that appeared more than once among the nine SAGE libraries, 11,156 tags representing 7,097 UniGene clusters were positioned onto chromosomes. A total of 43 and 55 clusters of differentially expressed genes were observed in squamous cell carcinoma and adenocarcinoma, respectively. The number of genes in each cluster ranged from 18 to 78 in squamous cell carcinomas and from 20 to 165 in adenocarcinomas. The size of these clusters varied from 1.8 Mb to 65.5 Mb in squamous cell carcinomas and from 1.6 Mb to 98.1 Mb in adenocarcinomas. Overall, the clusters with genes over-represented in tumors had an average of 3-4-fold increase in gene expression compared with the normal control. In contrast, clusters of genes with reduced expression had about 50-65% of the gene expression level compared with the normal. Examination of clusters identified in squamous cell lung cancer suggested that 9 of 15 clusters with overexpressed genes and 13 of 28 clusters with underexpressed genes were concordant with previously reported cytogenetic, comparative genomic hybridization or loss of heterozygosity studies. Therefore, at least a portion of the gene clusters identified via the transcriptome map most likely represented the transcriptional or genetic alterations occurred in the tumors. Integrating chromosomal mapping information with gene expression profiles may help reveal novel molecular changes associated with human lung cancer.
Carcinoma, Non-Small-Cell Lung↗
LASIK complications and the Internet: is the public being misled?
BACKGROUND: LASIK (Laser in Situ Keratomileusis) is a very popular combined surgical and laser procedure, which is used to correct myopia (shortsightedness) and hyperopia (farsightedness). There is concern that the public is being misled regarding the safety of the procedure. OBJECTIVES: To assess the quality and quantity of the information on complications on LASIK Web sites. METHOD: Serial analysis and evaluation of the authorship, content, and technical quality of the information on the complications of LASIK on 21 Web sites. RESULTS: Of the 21 LASIK Web sites visited, 17 were commercial. Of the 21 Web sites, 5 (24%) had no information on complications. Of the 16 sites that had information on complications the author of the information was clearly identified in 5 (31%), the content was only referenced in 2 (12.5%), and evidence of the information having been updated was only seen in 2 (12.5%). The quantity of information is generally minimal and the information itself is generally difficult to understand and locate. CONCLUSION: The quality and quantity of the information on the Web on the complications of LASIK are poor. More work is required to encourage clear, accurate, up-to-date, clearly authored, and well-referenced, balanced ophthalmic information.
Authorship↗
Predictive models of control strategies involved in containing indoor airborne infections.
Recently developed control measure modeling approaches for containing airborne infections, including engineering controls with respiratory protection and public health interventions, are readily amenable to an integrated-scale analysis. Here we show that such models can be derived from an integrated-scale analysis generated from three different types of functional relationship: Wells-Riley mathematical model, competing-risks model, and Von Foerster equation, both of the key epidemiological determinants involved and of the functional connections between them. We examine mathematically the impact of engineering control measures such as enhanced air exchange and air filtration rates with personal masking combined with public health interventions such as vaccination, isolation, and contact tracing in containing the spread of indoor airborne infections including influenza, chickenpox, measles, and severe acute respiratory syndrome (SARS). If enhanced engineering controls could reduce the basic reproductive number (R0) below 1.60 for chickenpox and 3 for measles, our simulations show that in such a prepared response with public health interventions would have a high probability of containing the indoor airborne infections. Combinations of engineering control measures and public health interventions could moderately contain influenza strains with an R0 as high as 4. Our analysis indicates that effective isolation of symptomatic patients with low-efficacy contact tracing is sufficient to control a SARS outbreak. We suggest that a valuable added dimension to public health inventions could be provided by systematically quantifying transmissibility and proportion of asymptomatic infection of indoor airborne infection. Practical Implications We have developed a flexible mathematical model that can help determine the best intervention strategies for containing indoor airborne infections. The approach presented here is scalable and can be extended to include additional control efficacies. If a newly emergent airborne infection should appear, the model could be quickly calibrated to data and intervention options at the early stage of the outbreak. Data could be provided from the field to estimate value of R0, the serial interval between cases, the distributions of the latent, incubation, and infectious periods, case fatality rates, and secondary spread within important mixing groups. The combination of enhanced engineering control measures and assigned effective public health interventions would have a high probability for containing airborne infection.
Air Pollution, Indoor↗
Carcinogenicity of tumor cell populations: origin of a putative H-2 isoantigenic loss variant tumor.
The properties of an unusual mouse tumor capable of extremely rapid and widespread spontaneous metastatic growth were recently described; this tumor, called MDAY-D2, at first appeared to be an H-2Kk loss variant of an (A X DBA/2)F1 (H-2KkDd) sarcoma called MDAY and was obtained by serial ip passage of MDAY in DBA/2 (KdDd) mice. The studies described here were concerned with the analysis of the origin of MDAY-D2; i.e., was it a true variant or a newly induced DBA/2 tumor? Several approaches were used, most of which exploited defined cell surface alloantigenic systems as natural genetic markers. The results indicated that MDAY-D2 was indeed a newly induced DBA/2 tumor and, furthermore, that MDAY was a homozygous A-strain tumor, probably a T-cell lymphoma. Thus a) MDAY was found to be Ly-1.2+, Ly-2.2+, and Thy-1.2+, but Ly-6.2-, whereas the opposite pattern was observed with MDAY-D2; b) MDAY possessed the private and public H-2 specificities associated with H-2k and H-2Dd, but not H-2Dk [i.e., it typed as an A-strain (H-2a) tumor, not as (A X DBA/2)F1]; c) MDAY-D2 possessed private and public specificities associated with H-2Kd and H-2Dd and was found to be H-2Kk-negative [i.e., it typed as a DBA/2 (H-2d) tumor]; d) serial injection of clonally derived ouabain-resistant H-2Kk-positive MDAY cells into DBA/2 hosts led to the rapid development of an MDAY-D2 (H-2d-positive) tumor that was fully ouabain-sensitive. Several findings did not support a contaminant theory to explain induction of MDAY-D2. The rapid induction of a tumor after injection of allogeneic tumor cells may have importance in relation to oncogenesis, tumor variant formation, and tumor progression. The results showed that tumor cells themselves can be potent carcinogens.
Animals↗
Induction of a tumor with greatly increased metastatic growth potential by injection of cells from a low-metastatic H-2 heterozygous tumor cell line into an H-2 incompatible parental strain.
An H-2 heterozygous sarcoma, MDAY, originally induced with methylcholanthrene in an (A X DBA/2)F1 ((H-2a X H-2d) hybrid host was selected for growth in the H-2d homoxygous parental DBA/2 strain by serial intraperitoneal transplantation of ascites tumor cells. An apparent variant, designated MDAY-D2, was obtained which showed the expected loss of the private and public H-2Kk haplotype antigens normally associated with the A strain parent and the original MDAY tumor. Comparison of the original and variant lines revealed a wide variety of a cell surface antigen and receptor differences. Both tumors were found to be highly anaplastic and histologically unclasssifiable. Examination of the two tumor lines growing in vivo revealed a remarkable difference in their metastatic growth potential. The original MDAY line showed little propensity to spread to any organ site, with the occasional exception of liver, after subcutaneous inoculation of (A X DBA/2)F1 mice. In striking contrast, there was a rapid and massive spread of MDAY-D2 to liver, spleen, lungs and kidneys within 12-16 days: liver and spleen could be totally replaced by tumor within 2-3 weeks. These characteristics were observed in both (A X DBA/2)F1 and DBA/2 mice. The tendency to metastasize, as well as loss of the H-2Kk haplotype, appeared stable and irreversible. Although the precise origin of MDAY-D2 is not clear, its metastasizing properties are unique, making it a useful and desirable model to study the biology of metastasis.
Animals↗
HC gp-39 gene is upregulated in glioblastomas.
Public databases of the Cancer Genome Anatomy Project were used to quantify the relative gene expression levels in glioblastoma multiforme (GBM) and normal brain by Serial Analysis of Gene Expression (SAGE). Analysis revealed HC gp-39 among the genes with the most pronounced changes of expression in tumor cells. Northern hybridization confirmed the results of computer analysis and showed that enhanced expression of the HC gp-39 gene was mainly in GBMs and occasionally in anaplastic astrocytomas. Neither SAGE nor Northern analysis revealed the presence of HC gp-39 mRNA in the glioblastoma cell line, thus the detection of increased quantities of this mRNA in GBMs may be associated with activated macrophages. Since the numbers of infiltrating macrophages and small vessel density are higher in glioblastomas than in anaplastic astrocytomas or astrocytomas, the HC gp-39 gene can be used as a molecular marker in the analysis of malignant progression of astrocytic gliomas.
Adipokines↗
Serum neuron-specific enolase in children with febrile seizures: time profile and prognostic implications.
Compared to publications of elevated levels of neuron-specific enolase (NSE) in adult patients with single seizures or epilepsy, data in children are rare. We studied serial NSE serum concentrations in children after febrile convulsions (FC). In addition, the predictive value of NSE levels in serum for recurrence of FC or further development of epilepsy was determined. Serum NSE levels were determined at (1) 0-2 h, (2) 6-8 h and (3) 20-24 h after a first or second FC in children aged 4 months to 6 years. Eighty-two patients (35 female, 47 male) aged four months to 5.7 years were included. Seventy-one children had generalized, and seven focal FC. The seizures in the remaining four patients could not be properly classified. During the follow-up of 14-28 months 13 patients had at least one more FC and in five epilepsy due to recurrent afebrile seizures was diagnosed. There was no statistically significant elevation of NSE concentration in the group of children with FC or the group with recurrent FC or epilepsy. The comparison of the NSE values at different times after FC did not show any significant differences either. It seems from our results that NSE activity cannot be used as a predictor for possible brain damage caused by FC and that it is not of predictive value considering further FC or development of epilepsy. We cannot confirm the published results of the elevation of NSE serum levels in adults with single seizures or status epilepticus.
Child, Preschool↗
The adventures of the Randy Professor and Angela the Sugar Mummy: sex in fictional serials in Ugandan popular magazines.
In 1996 newspaper vendors in Ugandan towns started selling a new kind of locally produced 'lifestyle' magazine. On the covers there were young, scantily dressed girls and inside news articles, fictional serials, lifestyle articles, agony aunt columns, etc. The new magazines gained an enormous popularity in a short space of time. Everywhere people were seen reading them and copies became brown and tattered from use. Using content analysis, we analyse the fictional serials which appeared in three of these magazines. We focus on these because they were the most sexually explicit type of content and, from a public health perspective, the most relevant with regard to HIV prevention. The stories were presented as simple entertainment, depicting the adventures of stereotypical characters. They provided people with explicit and unrestricted sexual fantasy which was, at the same time, devoid of any real risk. Although they could be interpreted as providing a discourse which challenged the main messages of HIV-prevention campaigns (sex is good for you, have as much of it as possible, and don't let condoms spoil the enjoyment), they also suggest that behaviour change may be more popular if sex and sexual health are not separated from sexual pleasure, and safe sex is promoted from a positive perspective (emphasis on sexual enjoyment) rather than a negative one (prevention of disease). The popularity of the magazines underscores the importance of entertainment value when discussing sex, and suggests alternative possibilities for disseminating health messages. Illustrated popular magazines such as those discussed here could be suitable as intervention, though they would need some adaptation to counter gender stereotypes and sexual violence.
HIV Infections↗
Improvements in diabetes processes of care and intermediate outcomes: United States, 1988-2002.
BACKGROUND: Progress of diabetes care is a subject of public health concern. OBJECTIVE: To assess changes in quality of diabetes care in the United States by using standardized measures. DESIGN: National population-based, serial cross-sectional surveys. SETTING: National Health and Nutrition Examination Survey (1988-1994 and 1999-2002) and the Behavioral Risk Factor Surveillance System (1995 and 2002). PARTICIPANTS: Survey participants 18 to 75 years of age who reported a diagnosis of diabetes. MEASUREMENTS: Glycemic control, blood pressure, low-density lipoprotein (LDL) cholesterol level, annual cholesterol level monitoring, and annual foot and dilated eye examination, as defined by the National Diabetes Quality Improvement Alliance measures. RESULTS: In the past decade, the proportion of persons with diabetes with poor glycemic control (hemoglobin A1c > 9%) showed a nonstatistically significant decrease of 3.9% (95% CI, -10.4% to 2.5%), while the proportion of persons with fair or good lipid control (LDL cholesterol level < 3.4 mmol/L [<130 mg/dL]) had a statistically significant increase of 21.9% (CI, 12.4% to 31.3%). Mean LDL cholesterol level decreased by 0.5 mmol/L (18.8 mg/dL). Although mean hemoglobin A1c did not change, the proportion of persons with hemoglobin A(1c) of 6% to 8% increased from 34.2% to 47.0%. The blood pressure distribution did not change. Annual lipid testing, dilated eye examination, and foot examination increased by 8.3% (CI, 4.0% to 12.7%), 4.5% (CI, 0.5% to 8.5%), and 3.8% (CI, -0.1% to 7.7%), respectively. The proportion of persons reporting annual influenza vaccination and aspirin use improved by 6.8 percentage points (CI, 2.9 percentage points to 10.7 percentage points) and 13.1 percentage points (CI, 5.4 percentage points to 20.7 percentage points), respectively. LIMITATIONS: Data are self-reported, and the surveys do not have all National Diabetes Quality Improvement Alliance indicators. CONCLUSION: Diabetes processes of care and intermediate outcomes have improved nationally in the past decade. But 2 in 5 persons with diabetes still have poor LDL cholesterol control, 1 in 3 persons still has poor blood pressure control, and 1 in 5 persons still has poor glycemic control.
Adolescent↗
Classification of hepatitis B virus genotypes by the PCR-Invader method with genotype-specific probes.
Hepatitis B virus is a worldwide public health problem. A simple and effective test to identify viral genotypes would greatly aid efforts to understand and control the spread of this disease. A serial invasive signal amplification reaction assay (PCR-Invader assay) was developed for distinguishing the known eight genotypes (A-H) and four subgenotypes (Aa, Ae, Ba, Bj) of hepatitis B virus (HBV). The preS/S and core regions were amplified by multiplex PCR and delivered to 12 wells containing genotype-specific Invader probes. By observing the fluorescence patterns in the wells, HBV sub/genotypes can be assigned. A total of 505 serum samples containing HBV/HBsAg in Japan was examined by PCR-Invader and compared the results with those from ELISA assays with monoclonal antibodies against epitopes on gene products of the preS2 region and with a genotype-specific probe assay (GSPA) based on the preS1 region. Genotypes determined by the PCR-Invader agreed with those of the ELISA method in 98.2% of cases and with the GSPA method in 97.1% of cases. Co-infection with two distinct genotypes was correctly identified by the PCR-Invader in four serum samples, as determined by GSPA. Thus, the PCR-Invader assay is a useful tool for detecting the 10 known HBV sub/genotypes.
Base Sequence↗
Lung cancer: the American view.
Bronchogenic carcinoma is a major public health problem in the United States, and the leading cancer killer in both men and women. In the early 1970s, the National Cancer Institute (NCI) sponsored multicentre clinical trials to assess the effects of screening by sputum cytology testing and serial chest X-ray examinations on lung cancer mortality in high-risk male smokers. Although more lung cancers were detected, more early stage 1 cancers were resected, and 5 year survival rates were improved in the screened populations than in unscreened controls, there were nearly equal numbers of advanced cancers, and mortality rates were not significantly different. Thus, mass screening to detect early lung cancer has not been pursued as public policy in the United States. In the 1980s, emphasis has shifted to efforts at lung cancer prevention through educational programs aimed at smoking prevention and cessation. In 1984, the NCI adopted a national goal of reducing lung cancer mortality by 50% by the year 2000. Strategy to achieve this is an intensive behaviour modification program to encourage a social climate for smoking abstinence, prevent initiation of smoking among children and adolescents and supply educational materials and encouragement through health care workers and community-based programs.
Carcinoma, Bronchogenic↗
Juvenile rheumatoid arthritis.
The heterogeneous nature of juvenile rheumatoid arthritis is further defined in publications from the past year. Decreased IL-10 production, an anti-inflammatory cytokine, and soluble IL-6 receptor are associated with systemic juvenile rheumatoid arthritis (JRA). IL-4 may have an anti-inflammatory role in the pathogenesis of pauciarticular JRA and may protect, along with IL-10, against the development of joint erosions. Active JRA is associated with lower levels of platelet activating factor acetylhydrolase, which may contribute to the loss of anti-inflammatory activity and increased risk of atherogenesis. The phase 3 clinical trial of etanercept confirmed its efficacy and safety in JRA. Intra-articular steroids are safe and effective in the treatment of JRA. Methotrexate does have disease-modifying effects. The risk of hepatotoxicity with methotrexate use increases with serial transaminase abnormalities and with obesity. Osteoclasts are responsible for joint erosions. Cyclosporine A, mycophenolate mofetil, and methotrexate are effective in the treatment of refractory uveitis. During the past year a number of scientific publications have contributed significantly to our understanding and treatment of juvenile rheumatoid arthritis.
Adolescent↗
[High throughput screening and analysis of prostate cancer-related genes through mining databases].
BACKGROUND & OBJECTIVE: Investigation of differentially expressed genes in prostate cancer tissues may help to understand the molecular mechanism of prostate cancer and provide diagnostic markers or new targets for therapy. The Cancer Genome Anatomy Project (CGAP) public database provides an unprecedented opportunity for cancer researchers to mine genes differentially expressed in cancer tissues by bioinformatic methods. This study was to explore the feasibility of incorporating the Internet-available Serial Analysis of Gene Expression (SAGE) and cDNA databases to find human prostate cancer-related genes. METHODS: SAGE digital gene expression displayer (DGED) and cDNA DGED were used to analyze differentially expressed (>5 folds) genes in malignant prostate tissues compared with normal prostate tissues. The SAGE tags were filtered by their confidence and our 3 criteria. To test the confidence of tags of virtual digital analysis for gene identification, the modified GLGI (generation of longer cDNA fragments from SAGE tags for gene identification) was used to get the cDNA 3' end downstream of 20 tags. Main functions of all candidate genes and their relations to prostate cancer were annotated. RESULTS: Fifty-three differentially expressed genes were screened out by SAGE DGED, 26 of them were up-regulated and 27 were down-regulated in prostate cancer; 28 differentially expressed genes were got by cDNA DGED, 15 of them were up-regulated and 13 were down-regulated in prostate cancer. CONCLUSION: Reasonable use of public databases by the Internet-available tools is a simple, effective approach to get cancer-related genes, and might provide useful clues for further investigation although the results require experimental validation.
DNA, Complementary↗