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A comprehensive panel of near-full-length clones and reference sequences for non-subtype B isolates of human immunodeficiency virus type 1.

Non-subtype B viruses cause the vast majority of new human immunodeficiency virus type 1 (HIV-1) infections worldwide and are thus the major focus of international vaccine efforts. Although their geographic dissemination is carefully monitored, their immunogenic and biological properties remain largely unknown, in part because well-characterized virological reference reagents are lacking. In particular, full-length clones and sequences are rare, since subtype classification is frequently based on small PCR-derived viral fragments. There are only five proviral clones available for viruses other than subtype B, and these represent only 3 of the 10 proposed (group M) sequence subtypes. This lack of reference sequences also confounds the identification and analysis of mosaic (recombinant) genomes, which appear to be arising with increasing frequency in areas where multiple sequence subtypes cocirculate. To generate a more representative panel of non-subtype B reference reagents, we have cloned (by long PCR or lambda phage techniques) and sequenced 10 near-full-length HIV-1 genomes (lacking less than 80 bp of long terminal repeat sequences) from primary isolates collected at major epicenters of the global AIDS pandemic. Detailed phylogenetic analyses identified six that represented nonrecombinant members of HIV-1 subtypes A (92UG037.1), C (92BR025. 8), D (84ZR085.1 and 94UG114.1), F (93BR020.1), and H (90CF056.1), the last two comprising the first full-length examples of these subtypes. Four others were found to be complex mosaics of subtypes A and C (92RW009.6), A and G (92NG083.2 and 92NG003.1), and B and F (93BR029.4), again emphasizing the impact of intersubtype recombination on global HIV-1 diversification. Although a number of clones had frameshift mutations or translational stop codons in major open reading frames, all the genomes contained a complete set of genes and three had intact genomic organizations without inactivating mutations. Reconstruction of one of these (94UG114.1) yielded replication-competent virus that grew to high titers in normal donor peripheral blood mononuclear cell cultures. This panel of non-subtype B reference genomes should prove valuable for structure-function studies of genetically diverse viral gene products, the generation of subtype-specific immunological reagents, and the production of DNA- and protein-based subunit vaccines directed against a broader spectrum of viruses.

Adolescent↗

Cystectomy for bladder cancer: a contemporary series.

PURPOSE: To validate the current TNM staging system, we analyzed our contemporary experience with 300 cystectomies. MATERIALS AND METHODS: The pathological material and medical records of 300 patients treated with cystectomy were reviewed, and the new TNM classification was adopted. RESULTS: The median followup of patients with no evidence of disease was 65 months, and overall survival rate was 45% with a median survival of 50 months. In a Cox regression analysis only patient age, pT stage and neoadjuvant chemotherapy were significant factors for survival. The disease specific survival was 67% with a median survival of 94 months. In a multiple proportional hazards analysis only pT stage and previous chemotherapy were significant factors of disease specific survival. A significant difference was seen in the overall and disease specific survival between patients with organ confined and nonorgan confined tumors. We did not observe a difference in the survival rate among patients with pT4a to pT3 tumors. Significant differences were not seen in survival rates between sexes or among patients of different age groups. Transitional cell carcinoma was the predominant histological type, and no significant difference was found in patient outcome among the different histological subtypes. CONCLUSIONS: Bladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

Adult↗

Organizational safety: which management practices are most effective in reducing employee injury rates?

PROBLEM: While several management practices have been cited as important components of safety programs, how much does each incrementally contribute to injury reduction? This study examined the degree to which six management practices frequently included in safety programs (management commitment, rewards, communication and feedback, selection, training, and participation) contributed to a safe work environment for hospital employees. METHOD: Participants were solicited via telephone to participate in a research study concerning hospital risk management. Sixty-two hospitals provided data concerning management practices and employee injuries. RESULTS: Overall, the management practices reliably predicted injury rates. A factor analysis performed on the management practices scale resulted in the development of six factor scales. A multiple regression performed on these factor scales found that proactive practices reliably predicted injury rates. Remedial measures acted as a suppressor variable. DISCUSSION: While most of the participating hospitals implemented reactive practices (fixing problems once they have occurred), what differentiated the hospitals with low injury rates was that they also employed proactive measures to prevent accidents. IMPACT ON INDUSTRY: The most effective step that hospitals can take is in the front-end hiring and training of new personnel. They should also ensure that the risk management position has a management-level classification. This study also demonstrated that training in itself is not adequate.

Accidents, Occupational↗

Prediction of distant residue contacts with the use of evolutionary information.

In this work we present a novel correlated mutations analysis (CMA) method that is significantly more accurate than previously reported CMA methods. Calculation of correlation coefficients is based on physicochemical properties of residues (predictors) and not on substitution matrices. This results in reliable prediction of pairs of residues that are distant in protein sequence but proximal in its three dimensional tertiary structure. Multiple sequence alignments (MSA) containing a sequence of known structure for 127 families from PFAM database have been selected so that all major protein architectures described in CATH classification database are represented. Protein sequences in the selected families were filtered so that only those evolutionarily close to the target protein remain in the MSA. The average accuracy obtained for the alpha beta class of proteins was 26.8% of predicted proximal pairs with average improvement over random accuracy (IOR) of 6.41. Average accuracy is 20.6% for the mainly beta class and 14.4% for the mainly alpha class. The optimum correlation coefficient cutoff (cc cutoff) was found to be around 0.65. The first predictor, which correlates to hydrophobicity, provides the most reliable results. The other two predictors give good predictions which can be used in conjunction to those of the first one. When stricter cc cutoff is chosen, the average accuracy increases significantly (38.76% for alpha beta class), but the trade off is a smaller number of predictions. The use of solvent accessible area estimations for filtering false positives out of the predictions is promising.

Algorithms↗

Path analysis of factors for delayed healing and nonunion in 416 operatively treated tibial shaft fractures.

UNLABELLED: A prospective observational study was done in 41 trauma centers. Four hundred sixteen patients with tibial shaft fractures were treated operatively and followed up for at least 6 months. Fifty-two (13%) cases of delayed healing or nonunion were reported. In such nonrandomized observational studies, multiple interrelationships exist between prognostic factors and patient outcomes. We used path analyses to investigate prognostic factors associated with the occurrence of delayed healing or nonunion. The most important factors were identified using multivariate regression analyses, and interrelationships between factors were illustrated using a path diagram. Fractures with open injuries less than and greater than 5 cm were 3.6 and 5.7 times as likely, respectively, to have delayed healing or nonunion as fractures with no skin injuries. The Müller-AO classification of fractures did not provide additional prognostic information. The risk of healing problems was doubled for fractures of the distal shaft and for fractures showing a postoperative diastasis. Treatment options showed an indirect effect on outcome with the occurrence of diastasis. A model for predicting delayed healing or nonunion is proposed. We encourage the use of path analysis in orthopaedics as a powerful visual technique to interpret data from observational studies. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗

Clinical analysis of multiple primary malignancies of the hypopharynx and esophagus.

PURPOSE: Because the capability to control squamous cell carcinomas of the head and neck has improved recently, the phenomenon of multiple primary malignancies of that region is now recognized with increasing frequency. We reviewed cases of multiple primary squamous cell carcinomas of the hypopharynx and esophagus with regard to their frequency, incidence, and prognosis. PATIENTS AND METHODS: We reviewed 104 cases of hypopharyngeal cancer to determine (1) if and when esophageal cancer occurred, (2) the classification of multiple tumors as metachronous or synchronous, and (3) tumor histology. RESULTS: In most cases of the metachronous type, esophageal cancer followed hypopharyngeal cancer within less than 3 years. Most cases of hypopharyngeal cancer were at an advanced stage, in contrast to esophageal cancer, which were all early stage. These cases had a poor prognosis despite various treatments causing local disease to be well controlled. Endoscopic esophageal mucosal resection was found to be an effective treatment for esophageal cancer, especially in superficial types. CONCLUSIONS: The prognosis and mild systemic damage after endoscopic esophageal mucosal resection compare favorably with surgery, radiation, or systemic chemotherapy.

Esophageal Neoplasms↗

Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts.

BACKGROUND: The abundance of monoclonal antibodies (mAb) and the routine use of quadruple stainings in flow cytometry allow stepwise analysis of bone marrow (BM) samples that are suspected for abnormal hematopoiesis. A screening phase that precedes lineage-specific classification phases should be sufficient to assess whether the BM has a normal or abnormal composition, as well as to identify the abnormal differentiation lineage. METHODS: For a quick and easy flow cytometric screening of BM samples, we selected six quadruple immunostainings that cover multiple differentiation stages of the B-cell, monocytic, granulocytic, and erythroid lineages: TdT/CD20/CD19/CD10 and CD45/CD34/CD19/CD22 for B cells, CD34/CD117/CD45/CD13.33 for precursor granulocytic and precursor monocytic cells (myelo/monoblasts), CD14/CD33/CD45/CD34 for monocytic cells, CD16/CD13/CD45/CD11b for granulocytic cells, and CD71/CD235a/CD45/CD117 for erythroid cells. RESULTS: The six quadruple immunostainings reveal specific staining patterns in normal BM, which allow the recognition of various subpopulations of the respective lineages. These staining patterns can be used as a frame of reference for recognition of normal and abnormal BM development. Examples of normal (age-related) variations in these otherwise stable staining patterns are presented together with several abnormal differentiation patterns. CONCLUSIONS: Although alternative immunostainings can be used (e.g., including NK- and T-cell markers), we feel that the selected six stainings represent a comprehensive and easy screening phase for quick identification of shifts in the composition of the studied differentiation lineages, reflecting age-related changes or disease-induced BM abnormalities.

Aging↗

Analysis and classification of disulphide connectivity in proteins. The entropic effect of cross-linkage.

An analysis and a classification of protein disulphide connectivity in a set of distinct sequences are presented. We analyse the number of disulphides per sequence, the number of disulphides per residue and the length of disulphide cross-linked loops. Observed connectivities are classified according to the different possible types of arrangement. In addition, we classify disulphide connectivity by physical models describing the arrangement of multiple disulphides. Firstly, we consider whether the features of native connectivity arrangement are describable by the likelihood of diffusive contact in the unfolded state. This is referred to as the diffusion model, and was originated by Kauzmann. A second model, effectively the inverse of the diffusion model, describes native connectivity arrangement as dominated by the entropic stabilisation effect of cross-linkage. This is referred to as the entropic model. Additionally, we compare the distribution of disulphide cross-linked loops and of loops formed by disulphide-like contacts. For short sequences (less than about 75 residues) native connectivities tend to have entropically more-stabilising arrangement features, whilst for longer sequences (greater than about 200 residues) the diffusion model is appropriate. We introduce the concept of arrangement entropy as a measure of the complexity of a connectivity.

Disulfides↗

Bethesda classification of cervicovaginal smears: reproducibility and viral correlates.

Fifty-five cervicovaginal smears from women with squamous intraepithelial lesions (SILs) were independently evaluated on two separate occasions by four cytopathologists using a binary classification system (the Bethesda system). Smears were categorized as low-grade (LSIL) or high-grade (HSIL) using previously published criteria. All women had subsequent cervical biopsies containing human papillomavirus (HPV) DNA amplified with the polymerase chain reaction and typed by restriction fragment polymorphism analysis. Three or more observers agreed on classification in 49 of 55 cases (87%); unanimous diagnoses were rendered in 31 cases (56%). Interobserver and intraobserver reproducibility ranged from fair to near-excellent (kappa values 0.40 to 0.63; 0.63 to 0.74, respectively). HPV types included HPV 16 (27%), 18 (7%), 31 (9%), 35 (4%), 39 (4%), 6 (10%), 11 (2%), novel types (30%), and multiple types (4%). High-risk HPV types (16, 18, 31, 35, and 39) were significantly associated (P = .03) with consensus HSIL diagnoses (agreement of three or more observers). This was primarily because of the strong association of HPV 16 with HSIL (P = .001). After excluding HPV 16, the other high-risk HPV types (18, 31, 35, and 39) were no longer significantly associated with consensus HSIL diagnoses (P > .5). Conversely, LSIL diagnoses were significantly associated with non-high-risk HPV types (all HPV types except 16, 18, 31, 35, and 39; P = .006). Binary cytological classification of cervicovaginal SILs is reproducible among cytopathologists. Such classification correlates well with most low-risk HPV types and with the prototypic high-risk HPV 16 but not with other high-risk HPV types.

Female↗

Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum.

To determine the prevalence of glucose intolerance in Korean women with gestational diabetes mellitus (GDM) between 6 and 8 weeks postpartum and identify which antepartum variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT), we prospectively performed 75 g oral glucose tolerance test (OGTT) between 6 and 8 weeks postpartum in women with GDM. WHO criteria were used for classification of glucose tolerance postpartum. Of 392 women with GDM were detected during the study period, 311 women participated in this study. Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Multiple logistic regression analysis revealed that pre-pregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT were independently associated with postpartum diabetes. Pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were independently associated with postpartum IGT. Our results support the importance of postpartum testing in Korean women with GDM, and demonstrated that impaired beta-cell function and pre-pregnancy obesity were associated with glucose intolerance at early postpartum.

Adult↗

Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology.

OBJECTIVES: The aim of this study was to analyze, in the same group of patients, the relationship between multiple variables of coronary lesion and results of exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND: Integrated evaluation of the relation between stress echocardiography results and angiographic variables should include not only the assessment of stenosis severity but also evaluation of other quantitative and qualitative features of coronary stenosis. METHODS: Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed. Stress echocardiography test was considered positive for myocardial ischemia when a new wall motion abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis to complete obstruction of the vessel was present in 153 patients, and 15 patients had normal coronary arteries. The observed angiographic variables included particular coronary vessel, stenosis location, the presence of collaterals, plaque morphology according to Ambrose classification, percent diameter stenosis and obstruction diameter as assessed by quantitative coronary arteriography. RESULTS: Covariates significantly associated with the results of physical and pharmacological stress tests included for all three stress modalities presence of collateral circulation, percent diameter stenosis and obstruction diameter, as well as lesion morphology (p < 0.05 for all, except collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic regression analysis, the strongest predictor of the outcome of exercise echocardiography test was only percent diameter stenosis (p = 0.0002). However, both dobutamine and particularly dipyridamole stress echocardiography results were associated not only with stenosis severity - percent diameter stenosis (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p = 0.0009). As all of stress echocardiography results were significantly associated with percent diameter stenosis, the best angiographic cutoff in relation to the results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS: Integrated evaluation of angiographic variables have shown that the results of dobutamine and dipyridamole stress echocardiography are not only influenced by stenosis severity but also, and even more importantly, by plaque morphology. The results of exercise stress echocardiography, although separately influenced by plaque morphology, are predominantly influenced by stenosis severity, due to a stronger exercise capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

Adult↗

Use of multiple correspondence analysis and cluster analysis to study dietary behaviour: food consumption questionnaire in the SU.VI.MAX. cohort.

Although the effects of individual foods or nutrients on the development of diseases and their risk factors have been investigated in many studies, little attention has been given to the effect of overall dietary patterns. The main objectives of this study were to identify dietary patterns and groups of subjects with similar food consumption habits, i.e. 'dietary profiles', using multiple correspondence analysis and cluster analysis. A food frequency questionnaire was sent to a large population-based sample (2923 women and 2,180 men), recruited among the 'SUpplementation en VItamines et Minéraux AntioXydants' (SU.VI.MAX.) cohort participants in France. The food items were dichotomised in order to focus the study on the highest levels of consumption. Multiple correspondence analysis allows the construction of principal components, which optimally summarise the data, and enables the construction of graphical displays. An interesting property of these graphical displays is that associations between food items can be observed on various projection planes, each category of each food item being located at the centre of gravity of the subjects corresponding to this category. An ascending hierarchical classification was unsuccessfully tried in order to determine clusters from these principal components. Therefore, a 'dissection' of the cloud of points was performed according to the orientation of the axes, providing a readily interpretable eight-dietary profiles typology for each sex. This statistical approach allows identification of particular dietary patterns and dietary profiles, which might be more appropriate in studies of diet-disease associations than the single food or nutrient approach that has dominated past epidemiological research.

Adult↗

VEGA, the genome browser with a difference.

The Vertebrate Genome Annotation (Vega) database is a community resource for browsing manual annotation from a variety of vertebrate genomes of finished sequence (http://vega.sanger.ac.uk). Vega is different from other genome browsers as it has a standardised classification of genes which encompasses pseudogenes and non-coding transcripts. The data is manually curated, which is more accurate at identifying splice variants, pseudogenes poly(A) features, non-coding and complex gene structures and arrangements than current automated methods. The database also contains annotation from regions, not just whole genomes, and displays multiple species annotation (human, mouse, dog and zebrafish) for comparative analysis. Vega encourages community feedback that results in annotation updates and manual annotation of finished vertebrate sequence.

Animals↗

Melanocytic nevi and risk of cutaneous malignant melanoma in southern Spain.

The main objective of this study was to assess whether cutaneous malignant melanoma (CMM) shows a stronger relation with the melanocytic nevi count at the site where CMM was diagnosed than with the melanocytic nevi count at other sites, stratifying by histologic CMM type, in a southern Mediterranean population. Cases and controls were selected from a population in southern Spain in 1988-1993. The study population included 116 incident cases with non-familial CMM (International Classification of Diseases 9th Revision (ICD-9) code 172), and 116 controls matched 1:1 for sex and age (+/- 4 years). Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface by clinical skin examination performed by a dermatologist. Crude and multiple risk factor-adjusted odds ratios and 95% confidence intervals were computed by conditional logistic regression analysis. After adjustment by skin type, unexposed skin color, and sun exposure, CMM was found to occur significantly more frequently in individuals with a high number of melanocytic nevi at the same site where CMM originated (odds ratio (OR) for >8 nevi = 12.0, 95% confidence interval (CI) 1.3-108.2). The ability to predict the number of melanocytic nevi on different anatomic sites on CMM, but excluding the CMM cases on each corresponding site, was also examined. A significant trend with the number of nevi on the anterior surface of thighs was found (OR for >4 nevi = 4.5, 95% CI 1.4-14.9). Melanocytic nevi count on the melanoma site was the variable most closely related to superficial spreading melanoma subtype (SSM) (OR for >8 nevi = 82.19, 95% CI 2.72-2,454). On the other hand, the number of melanocytic nevi on the melanoma site was unrelated to risk of CMM subtypes other than SSM. These results support the hypothesis that nevi are an important risk factor for melanoma, especially SSM, in populations with a darker ethnic background.

Case-Control Studies↗

The University of North Carolina caries risk assessment study: caries increments of misclassified children.

The University of North Carolina caries risk assessment was conducted between 1986 and 1989 with 5000 children initially in grades 1 and 5 from low fluoride sites in South Carolina and Maine. Clinical, microbiologic, behavioral, and demographic factors served as independent variables used in logistic multiple regression models to determine the predicted caries risk classification of each child. The 3-yr DMFS increment of each child was the dependent variable, and the 20-25% of those in each cohort with the highest increment were considered the high risk group. Sensitivity and specificity values averaged 0.60 and 0.83 respectively, indicating the misclassification of substantial numbers of children. This paper reports analysis of the DMFS increments of the misclassified children. The majority of children had DMFS increments within one or two surfaces of the classification cut points. Many false negative children had increments composed entirely of filled surfaces, often of minimal extent and without evidence of previous decay. Many false positive children had increments composed of decayed surfaces and would have benefitted from being identified as high risk and assigned to a preventive program. Other false positive children had sealants placed after the baseline examination that undoubtedly reduced their true increment. It is concluded that the consequences of misclassification are not serious for most children in this study.

Child↗

Risk factors for healing of duodenal ulcer under antacid treatment: do ulcer patients need individual treatment?

In order to identify the risk factors affecting the healing of duodenal ulcer, a clinical trial with effective dose of antacid was carried out in 53 patients. Duration of ulcer history, number of relapses, duration of the last and present relapse, number, duration and severity of pain attacks in the present ulcer relapse, pain radiation to back, vomiting, appetite, smoking habit, intake of analgesics and previous haemorrhage were registered. Number of ulcers, ulcer depth, bublar narrowing, erosions, duodenitis at initial endoscopy and healing of ulcer were assessed by one endoscopist. Basic and peak acid output were measured. The extent of duodenitis on the site opposite the ulcer was determined by histological examination. Sixty per cent of the duodenal ulcers were healed after three weeks. By univariate analysis, the following factors affect the healing; pain radiation to back and pain duration during treatment (p less than 0.001), multiple or deep ulcers, narrowing of duodenal bulb (p less than 0.01), number of pain attacks and poor appetite (p less than 0.05). By the stepwise logistic regression model, the following factors were selected as predictors for healing of duodenal ulcer with 76% correct classification: pain radiation to back (p = 0.002), deep ulcer (p = 0.013), multiple ulcers (p = 0.028). Number of cigarettes/day (p less than 0.007) and male sex (p = 0.036). By this model, the prediction of healing could be accurately assessed in 78% in a new sample. Individual treatment should be carried out on the basis of these factors.

Aluminum Hydroxide↗

A biphasic pattern of gene expression during mouse retina development.

BACKGROUND: Between embryonic day 12 and postnatal day 21, six major neuronal and one glia cell type are generated from multipotential progenitors in a characteristic sequence during mouse retina development. We investigated expression patterns of retina transcripts during the major embryonic and postnatal developmental stages to provide a systematic view of normal mouse retina development, RESULTS: A tissue-specific cDNA microarray was generated using a set of sequence non-redundant EST clones collected from mouse retina. Eleven stages of mouse retina, from embryonic day 12.5 (El2.5) to postnatal day 21 (PN21), were collected for RNA isolation. Non-amplified RNAs were labeled for microarray experiments and three sets of data were analyzed for significance, hierarchical relationships, and functional clustering. Six individual gene expression clusters were identified based on expression patterns of transcripts through retina development. Two developmental phases were clearly divided with postnatal day 5 (PN5) as a separate cluster. Among 4,180 transcripts that changed significantly during development, approximately 2/3 of the genes were expressed at high levels up until PN5 and then declined whereas the other 1/3 of the genes increased expression from PN5 and remained at the higher levels until at least PN21. Less than 1% of the genes observed showed a peak of expression between the two phases. Among the later increased population, only about 40% genes are correlated with rod photoreceptors, indicating that multiple cell types contributed to gene expression in this phase. Within the same functional classes, however, different gene populations were expressed in distinct developmental phases. A correlation coefficient analysis of gene expression during retina development between previous SAGE studies and this study was also carried out. CONCLUSION: This study provides a complementary genome-wide view of common gene dynamics and a broad molecular classification of mouse retina development. Different genes in the same functional clusters are expressed in the different developmental stages, suggesting that cells might change gene expression profiles from differentiation to maturation stages. We propose that large-scale changes in gene regulation during development are necessary for the final maturation and function of the retina.

Animals↗

DNA content by flow cytometry in gastric carcinoma: pathology, ploidy and prognosis.

BACKGROUND/AIMS: The prognostic relevance of histopathologic findings in gastric carcinoma is well established. Studies on DNA-ploidy are still scanty and contradictory. METHODOLOGY: Histopathologic parameters, DNA ploidy and S-phase were evaluated in 78 cancer patients curatively resected, using formalin-fixed paraffin-embedded tissue. RESULTS: Thirty-nine tumors (50%) were aneuploid. No significant correlation was found between histologic data and ploidy, but tumors with nodal involvement were more frequently aneuploid. In univariate analysis, tumor location (p=0.05), tumor size (p=0.01), differentiation grade (p=0.02), Lauren classification (p=0.01), deeper infiltration of gastric wall (p=0.001), nodal affectation (p=0.0000) and number of lymph nodes (p=0.01), TNM stage (p=0.0000), type of gastrectomy performed (p=0.04), and DNA ploidy (p=0.04) significantly influenced survival. S-phase values had no effect on prognosis. In the multiple regression model, factors independently associated with survival were TNM stage (p=0.0009), nodal affectation (p=0.01) and, marginally, ploidy (p=0.08). CONCLUSIONS: In gastric carcinoma curatively resected, the more relevant prognostic factors were stage and nodal involvement. Fifty percent of the tumors were aneuploid. Aneuploidy was significantly associated with poorer prognosis.

Adult↗