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A new wound-based severity score for diabetic foot ulcers: A prospective analysis of 1,000 patients.

OBJECTIVE: Several well-accepted classification systems are available for diabetic foot ulcers. However, there are only a few and scientifically not validated severity scores. The aim of this study was to establish a new wound-based clinical scoring system for diabetic foot ulcers suitable for daily clinical practice anticipating chances for healing and risk of amputation. RESEARCH DESIGN AND METHODS: Four clinically defined parameters, namely palpable pedal pulses, probing to bone, ulcer location, and presence of multiple ulcerations, were prospectively assessed in 1,000 consecutive patients. In the next step, a new diabetic ulcer severity score (DUSS) was created from these parameters. Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while probing to bone was defined as yes (scored as 1) or no (scored as 0). The site of ulceration was defined as toe (scored as 0) or foot (scored as 1) ulcer. Patients with multiple ulcerations were graded as 1 compared with those with single ulcers (scored as 0). The DUSS was calculated by adding these separate gradings to a theoretical maximum of 4. Wounds were followed-up for 365 days or until healing or amputation if earlier. Probability of healing and risk of amputation were calculated by the Kaplan-Meier method. RESULTS: Uni- and multivariate analyses showed a significantly higher probability of healing for patients with palpable pulses, no probing to bone, toe ulcers, and absence of multiple ulcerations. When patients were divided into subgroups with the same DUSS, we found significantly different probabilities for healing. We showed a decreasing probability of healing for ulcers with a high DUSS, concurrent with increasing amputation rates. An increase in the DUSS by one score point reduced the chance for healing by 35%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the need for surgery or hospitalization. CONCLUSIONS: The DUSS categorizes different ulcers into subgroups with specific severity and similar clinical outcome. Using this score, the probabilities for healing, amputation, need for surgery, and hospitalization are predictable with high accuracy. This might be useful for the anticipation of health care costs and for comparison of subgroups of patients in clinical studies.

Adult↗

Soft tissue masses in patients with multiple myeloma: a fine-needle aspiration study of 30 cases with flow cytometry and clinical correlation.

BACKGROUND: To the authors' knowledge, the prognostic significance of plasma cell cytology in soft tissue (ST) masses from patients with multiple myeloma (MM) is unknown. Myeloma patients usually are monitored by bone marrow (BM) aspirates and biopsies to assess plasma cell differentiation, tumor burden, and response to treatment. Monitoring of ST lesions by fine-needle aspiration (FNA) is not performed routinely. The objective of the current study was to examine ST masses in MM patients using FNA and to classify and determine the prognostic significance of MM in these lesions based on cytologic features. METHODS: FNAs of 30 ST masses from 27 patients with a history of MM were examined for disease involvement. In the patients with MM, the cytologic features were evaluated and the lesions were graded as low grade, intermediate grade, or high grade based on the classification of Bartl et al. for MM in BM specimens. Concurrent BM samples as well as cytogenetic and flow cytometric results also were reviewed. RESULTS: Twenty-seven of the FNA specimens (90%) were positive for MM, and three specimens (10%) were negative (one case each of lipoma, keratinous cyst, and aspergillosis). Among the MM cases, 5 (18.5%) were low grade, 15 (55.6%) were intermediate grade, and 7 (25.9%) were high grade (blastic MM). Simultaneous BM involvement was present in 23.5% of low-grade MM (4 of 17 cases), 35.3% of intermediate-grade MM (6 of 17 cases), and 71% of high-grade MM (5 of 7 cases). Clinically, 10 of 24 patients (42%) died within 9 months (median, 2 months). Patients with high-grade myeloma (blastic MM) in ST masses appeared to have worse survival; 43% (3 of 7 patients) died by a median time of 2 months, compared with 12% of patients with low-grade and intermediate-grade MM (2 of 17 patients). CONCLUSIONS: FNA of ST masses appears to improve the management of MM patients by providing diagnostic material, samples for ancillary studies, and prognostic information. ST MM can be classified reliably into grades of prognostic significance utilizing the classification of Bartl et al. Intermediate-grade MM was the most frequent subtype present in ST masses.

Adult↗

Clinicopathology of spinocerebellar degeneration: its correlation to the unstable CAG repeat of the affected gene.

The recent advances in gene analysis have greatly facilitated the classification of autosomal dominant spinocerebellar ataxia (SCA). Analyses of linkage in large families with SCA have assigned gene foci to at least 8 chromosomes. One gene is located in the short arm of chromosome 6 (6p22-p23) and causes spinocerebellar ataxia type 1 (SCA1). A gene in the long arm of chromosome 14 (14q24.3-q32) underlies Machado-Joseph disease (MJD). A third gene locus is assigned to the short arm of chromosome 12 (12p2-pter) causing dentatorubropallidoluysian atrophy (DRPLA). The gene for spinocerebellar ataxia type 2 (SCA2) is located in the 12q23-24. Subsequently, a sporadic counterpart of hereditary olivopontocerebellar atrophy of the Menzel type is clearly defined, and all the syndromes (non-hereditary olivopontocerebellar atrophy, striatonigral degeneration and Shy-Drager syndrome) are now lumped under the term of multiple system atrophy (MSA). Oligodendroglial cytoplasmic inclusions appear to be specific for and diagnostic of MSA. As the clinical features in SCA are variable and often appear to overlap with one another, which makes accurate classification difficult if not possible, the genotype is required for their unequivocal classification. However, major neuropathological features clearly distinguish SCA1 from SCA3/ MJD cases; the medial segment of the globus pallidus and intermediolateral column lesions in SCA3/MJD, and inferior olive and cerebellar cortical degeneration in SCA1. It has been stated that neurodegeneration in SCA3/MJD is more homogeneous than in SCA1 or SCA2 and that degeneration of the pallidoluysian system is not present in the latter. The pertinent pathology in each of the three types of SCA is illustrated. The background of clinicopathology and genetic analysis of dentatorubropallidoluysian atrophy is also reviewed.

Chromosome Mapping↗

GARBAN II: an integrative framework for extracting biological information from proteomic and genomic data.

Genomic and proteomic analyses generate a massive amount of data that requires specific bioinformatic tools for its management and interpretation. GARBAN II, developed from the previous GARBAN platform, provides an integrated framework to simultaneously analyse and compare multiple datasets from DNA microarrays and proteomic studies. The general architecture, gene classification and comparison, and graphical representation have been redesigned to ensure a user-friendly feature and to improve the capabilities and efficiency of this system. Additionally, GARBAN II has been extended with new applications to display networks of coexpressed genes and to integrate access to BioRag and MotifScanner so as to facilitate the holistic analysis of users' data.

Animals↗

[A population-based study on variations in the use of adjuvant radiotherapy in breast cancer patients].

AIM: The assessment of the compliance with consensus recommendations for adjuvant radiation therapy among women with breast cancer. The study is based on data obtained in a population-based cohort-study, which was performed to evaluate the quality of health care for patients with breast cancer. PATIENTS AND METHODS: About one million inhabitants live in the study region Eastern Thuringia, 2,031 cases with invasive breast cancer without distant metastasis (MO) or inflammatory spread were registered from 1995 to 2000. Out of these 1,700 with complete documentation of covariates were included in multivariate analysis. To examine the simultaneous influence of all clinical factors and "caseload" on the likelihood to receive adjuvant radiation therapy a logistic regression model was fitted for radiation therapy after mastectomy. In order to describe the impact of each individual clinic on treatment decision as "caseload" was replaced by the clinics with more than 30 primary treatments. RESULTS: Following breast conserving therapy (BCT) 90.6% of the patients received adjuvant radiation therapy. In the univariate analysis older age was negatively associated with the use of radiation therapy among women with BCT (Table 1). Furthermore, comorbid conditions were negatively associated with the use of radiation therapy. For all other cofactors no associations were found. Subsequent to mastectomy 33.0% of the women underwent radiation therapy (Table 2). Associations between the use of radiation therapy and age, tumor category, number of positive lymph nodes, multiple tumors, histologic differentiation grade, residual tumor as well as hormone receptor status were found. In the multivariate analysis only older age (>/= 70 years) was identified as negative indicator for the utilization of radiation therapy. Among patients with mastectomy increasing tumor size was a positive predictor on radiation therapy (Table 3). In addition more than three positive lymph nodes, multiplicity, poor histologic differentiation grade (G3/4), medial localization, and younger age (35-49 years) were positive predictors for the application of radiation therapy. For R-classification, hormone receptor status and comorbidity no influence on the use of radiation therapy was observed. Among clinics adjusted for case-mix variations in the compliance of treatment recommendation both following BCT and mastectomy were found (Figure 1). CONCLUSION: Following BCT compliance with treatment recommendations regarding radiation therapy was high. Women in older age or with comorbidities received less often radiation therapy. Subsequent to mastectomy indicators for the use of radiation therapy were identified. Among clinics differences in the adherence to treatment recommendations were observed.

Adult↗

Fuzzy logic-based tumor-marker profiles improved sensitivity in the diagnosis of lung cancer.

BACKGROUND: The aim of this study was to improve the diagnostic efficiency of tumor markers in the diagnosis of lung cancer, by the mathematical evaluation of a tumor marker profile employing fuzzy logic modelling. METHODS: A panel of four tumor markers, i.e., carcinoembryonic antigen (CEA), cytokeratin 19 antibody (CYFRA 21-1), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC) and, additionally, C-reactive protein (CRP), was measured in 175 newly diagnosed lung cancer patients with different histological types and stages. Results were compared with those in 120 control subjects, including 27 with chronic obstructive pulmonary diseases (COPD), 65 with pneumoconiosis, and 11 persons with acute inflammatory lung diseases. A classificator was developed using a fuzzy-logic rule-based system. RESULTS: Application of the fuzzy-logic rule-based system to the tumor marker values of CYFRA 21-1, NSE, and CRP yielded an increase in sensitivity of approximately 20%, i.e., 92%, compared with that of the best single marker, CYFRA 21-1(sensitivity, 72%). The corresponding specificity was 95%. The fuzzy classificator significantly improved the sensitivity of the tumor marker panel in stages I and IIIa for non-small-cell lung cancer, as well as in "limited disease" status for small-cell lung cancer. Also, the diagnosis of other stages of lung cancer was enhanced. CONCLUSION: Fuzzy-logic analysis was proven to be more powerful than the measurement of single markers alone or combinations using multiple logistic regression analysis of all markers. Therefore, fuzzy logic offers a promising diagnostic tool to improve tumor marker efficiency.

Aged↗

Local understandings of adult diarrhoeal disease and its treatment in an area of high HIV-seroprevalence in Zambia.

We set out to investigate the extent to which cultural constructs might determine treatment-seeking for diarrhoea in the poorer populations of Lusaka, Zambia. This paper describes these concepts and perceptions and outlines a classification of such illnesses, together with an analysis of its implications for understanding treatment choice. Data were derived from focus group discussions, a household survey, a survey of practitioners of traditional medicine and interviews with local residents attending an urban health centre with persistent diarrhoea. The classification is based on symptoms and perceptions of aetiology. While resulting categories convey imperatives for treatment choice, it is clear that individuals with diarrhoeal illnesses seek treatment from multiple sources. This may be because any single illness may fit more than once category, or because unrelenting ill-health engenders desperate behaviour. The cultural constructs do not fully explain treatment choice and attitudes to prevention, but could be used to improve communication regarding public health and treatment strategies.

Adult↗

Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update.

In the last two decades, progress in the diagnosis of von Willebrand disease (VWD) came from the rapidly developing field of molecular techniques that allowed the first phenotype-genotype correlations. In particular, structural and functional defects of von Willebrand factor (VWF) that underlie VWD type 2 and their molecular basis not only helped to understand the pathophysiology of VWD but also the complex post-translation processing of VWF and the multiple VWF functions. In contrast to the dramatic development of molecular techniques, improvement of methods for phenotypic description, a prerequisite for phenotype-genotype comparisons, has been neglected. The gold standard to differentiate VWD type 2 from type 1 and between diverse type 2 subtypes is the electrophoretic analysis of VWF multimers, a demanding technique that itself is not easily standardized but of crucial relevance for correct classification. This article summarizes the current knowledge on phenotype-genotype correlations as well as up-to-date phenotypic and genotypic methods in the diagnosis of VWD.

Genotype↗

Comparison of prevalence for paraumbilical vein patency in patients with viral and alcoholic liver cirrhosis.

OBJECTIVES: The patent paraumbilical vein (PUV) is a venous collateral that is often found in patients with cirrhosis and portal hypertension. It can be effectively demonstrated by conventional ultrasonography (US). We conducted this prospective study to elucidate the prevalence and etiology of PUV patency for cirrhotic patients. METHODS: From August, 1997, to July, 1998, one of the authors (S.-N.L.) observed PUV patency for all cirrhotic patients during routine upper abdominal US examination. All cirrhotic patients diagnosed with portal hypertension were further analyzed. Portal hypertension was diagnosed by sonographic evidence of splenomegaly or ascites, or endoscopic varices. Cases presenting with hepatocellular carcinoma and sonographic evidence of prehepatic portal hypertension were excluded. Once a PUV patency with a diameter of > or = 3 mm was suspected based on conventional US, it was confirmed by color Doppler US. Of the 493 cirrhotic patients examined, 252 with portal hypertension and without hepatoma were enrolled in this study. RESULTS: Significant PUV patency was detected in 11.1% of the enrolled patients (28 of 252). With univariate analysis, a significantly higher prevalence was demonstrated for alcoholic patients (p < 0.0001), whereas prevalence was relatively low for those with chronic hepatitis B or C infection (p = 0.0159). A trend toward increased prevalence was noted with Child-Pugh classification (p = 0.001). Furthermore, a higher prevalence was noted in younger cirrhotic patients (p = 0.0037). Alcoholism was still a significant factor despite adjustment of Child-Pugh classification using multiple logistic regression, (OR = 3.88, 95% CI = 1.34-8.55). CONCLUSION: A significantly higher prevalence of PUV patency was demonstrated for patients with alcohol-induced liver cirrhosis in comparison to those with postviral cirrhosis.

Adult↗

Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus.

Human papillomavirus (HPV) can be detected by amplification of viral DNA. A novel PCR primer set generating a short PCR fragment (SPF PCR) was used for amplification of a fragment of only 65 bp from the L1 region and permitted ultrasensitive detection of a broad spectrum of HPV genotypes. The intra- and intertypic sequence variations of the 22-bp interprimer region of this amplimer were studied. Among 238 HPV sequences from GenBank and clinical specimens, HPV genotypes were correctly identified based on the 22-bp sequence in 232 cases (97.2%). Genotype-specific probes for HPV genotypes 6, 11, 16, 18, 31, 33 to 35, 39, 40, 42 to 45, 51 to 54, 56, 58, 59, 66, 68, 70, and 74 were selected, and a reverse hybridization line probe assay (LiPA) (the INNO-LiPA HPV prototype research assay) was developed. This LiPA permits the use of amplimers generated by the SPF as well as the MY 09/11 primers. The assay was evaluated with a total of 1, 354 clinical specimens, comprising cervical scrapes (classifications ranging from normal cytology to severe dyskaryosis) and formalin-fixed, paraffin-embedded cervical carcinoma samples. LiPA results were highly concordant with sequence analysis of the SPF amplimer, genotype-specific PCR, and sequence analysis of amplimers generated by MY 09/11 primers. The sensitivity of the SPF primers was higher than that of the GP5(+)/6(+) primers over a broad range of HPV types, especially when multiple HPV genotypes were present. In conclusion, the SPF LiPA method allows extremely sensitive detection of HPV DNA as well as reliable identification of HPV genotypes in both cervical smears and paraffin-embedded materials.

Base Sequence↗

Severity of illness models for respiratory syncytial virus-associated hospitalization.

The objective of this investigation was to examine the feasibility of multivariate severity of illness models for pediatric patients hospitalized with respiratory syncytial virus (RSV) infection. From a preexisting retrospective cohort study database, all infants and children 2 yr of age or younger with community-acquired RSV infection admitted to the University of Michigan's C. S. Mott Children's Hospital during nine epidemics were examined. The study group consisted of 802 hospitalized patients younger than 2 yr of age with community-acquired RSV infection; 182 (23%) patients had prolonged hospital length of stay defined as 7 d or greater. Multivariate logistic regression modeling of nine variables measurable during the first hospital day was strongly associated with prolonged hospitalization (p < 0.0001). Receiver operator characteristic curve analysis resulted in an area under the curve of 0.894, indicating excellent model discrimination. Goodness-of-fit testing indicated excellent model calibration for observed versus predicted outcomes (p = 0.216). We conclude that severity of illness models for RSV-associated hospitalization with excellent predictive properties in terms of classification, discrimination, and calibration are possible. Further study is required to determine if such models are generalizable across multiple centers and epidemics.

Female↗

Cornell Medical Index score observed among Japanese nursing students.

Purpose of this study was to survey subjective health problems occurring among Japanese nursing students. Data collected with the self-administered Cornell Medical Index Health Questionnaire Japanese version (JCMI) from 102 Japanese first year nursing students were analyzed. The total CMI score (section A-R) ranged from 2-108 with an average of 23.1 (SD = 15.9). The mean CMI for physical (section A-L) and psychological health complains (section M-R) were 15.7 (SD = 11.8) and 7.3 (SD = 6.1), respectively. Two-way analysis of variances with multiple comparison of means revealed significant relationships between age and psychological health complaints and both physical and overall health complaints. The older nursing students reported more physical and overall health complaints than the youngest. The nursing students who reported more complaints about psychological health also reported significantly more physical and overall health complaints. A comparison of Fukamachi's and Brodman's criteria for classification of neurotic traits is discussed. Findings from this study support the hypothesis that psychological health is somewhat reacted to physical health.

Adolescent↗

[Discriminative value for AIDS case of erythrocyte sedimentation rate, immunoglobulins IgA and IgM, and beta 2-microglobulin in combination with the CD4+ lymphocyte count].

OBJECTIVE: To establish the probability to discriminate the evolution to "AIDS case" in relation to the common laboratory parametres in the follow-up of the HIV infection. MATERIAL AND METHODS: We have studied a cohort of 118 patients (1986-95) with HIV infection, 14 of them (12%) had clinical criteria for AIDS (CDC/93) during the follow-up. Clinical evaluations and CD4+ and CD8+ lymphocytes, beta 2M, IgG, IgA, IgM and E.S.R determinations were done. Multivariate analysis (RSIGMA) was done. with the initial laboratory values, according to the clinical diagnostic (AIDS and NO AIDS) done during the follow-up. RESULTS: By multiple logistic regression those laboratory variables with more predictor value for "AIDS CASE" were selected. With the initial value of these variables (E.S.R., beta 2M, IgA, IgM and CD4+ lymphocytes) and the clinical diagnostic of AIDS done during the follow-up, we did the linear discriminatory analysis between two groups (AIDS, NO AIDS) obtaining generalized distance between both groups of 3,4609 and a probability of classification error of 4%. A very significant difference (p < 0.001) was obtaining when we compare the variables' mean of each of the clinical groups. CONCLUSION: In the HIV infection the values of ESR, beta 2M, IgA and IgM in combination with the absolute value of the CD4+ lymphocytes allows to discriminate those patients who will develop AIDS with a probability of classifications error of 4%. This has clinical interest in absence of viral load and helps to take therapeutical decisions.

Acquired Immunodeficiency Syndrome↗

Identifying genes that contribute most to good classification in microarrays.

BACKGROUND: The goal of most microarray studies is either the identification of genes that are most differentially expressed or the creation of a good classification rule. The disadvantage of the former is that it ignores the importance of gene interactions; the disadvantage of the latter is that it often does not provide a sufficient focus for further investigation because many genes may be included by chance. Our strategy is to search for classification rules that perform well with few genes and, if they are found, identify genes that occur relatively frequently under multiple random validation (random splits into training and test samples). RESULTS: We analyzed data from four published studies related to cancer. For classification we used a filter with a nearest centroid rule that is easy to implement and has been previously shown to perform well. To comprehensively measure classification performance we used receiver operating characteristic curves. In the three data sets with good classification performance, the classification rules for 5 genes were only slightly worse than for 20 or 50 genes and somewhat better than for 1 gene. In two of these data sets, one or two genes had relatively high frequencies not noticeable with rules involving 20 or 50 genes: desmin for classifying colon cancer versus normal tissue; and zyxin and secretory granule proteoglycan genes for classifying two types of leukemia. CONCLUSION: Using multiple random validation, investigators should look for classification rules that perform well with few genes and select, for further study, genes with relatively high frequencies of occurrence in these classification rules.

Colonic Neoplasms↗

Alcoholic beverage type, recall period effects and functional disability: evidence from the 1983 NHIS.

To replicate a Canada Health Survey (CHS) study that found beer drinking was associated with lower morbidity, National Health Interview Survey (NHIS) data for 19,462 persons were used to examine associations between functional disability and beverage specific ethanol consumption. A functional disability index consisting of morbidity and symptom coping events reported for 2 weeks prior to the NHIS interview was constructed. Alcohol consumption was reported for the same period as disability (coincident recall), or for the 2 weeks prior to the respondent's last drink during the past year (antecedent recall). The analysis controlled for confounders using direct standardization and multiple logistic regression. The results of this investigation were not consistent with the CHS study. Former drinkers and antecedent recall drinkers reported greater disability rates than either non-drinkers or coincident recall drinkers. Antecedent recall drinkers exhibiting a preference for beer and wine were, respectively, 40 and 80 percent more likely to be disabled than non-drinkers. Further, this study found no evidence of a protective effect among any subgroup of drinkers. The finding of a significant interaction between alcohol consumption and alcohol recall period suggests that epidemiologic studies should give greater attention to the classification of drinker groups by proximity of alcohol consumption.

Activities of Daily Living↗

Mitochondrial encephalomyopathies: clinical and molecular analysis.

The classification of mitochondrial encephalomyopathies relied upon clinical, biochemical, and histological features until the discovery of mitochondrial DNA defects in 1988. Since then, an outburst of molecular genetic information has aided our understanding of the pathogenesis and the classification of these heterogeneous disorders. Novel concepts of maternal inheritance, mitochondrial DNA (mtDNA) heteroplasmy, tissue distribution, and threshold have explained many of the clinical characteristics. The discovery of point mutations, large-scale mtDNA deletions, duplications, and autosomally inherited disorders with multiple mtDNA deletions have revealed new genetic phenomena. Despite our rapidly expanding understanding of the molecular genetic defects, many questions remain to be explored to fill the gap in our knowledge of the relationship between genotype and clinical phenotype.

DNA, Mitochondrial↗

Relationship of glycemic control to total diabetes-related costs for managed care health plan members with type 2 diabetes.

OBJECTIVE: Glycosylated hemoglobin (A1c) is a well-established measure of glycemic control, and evidence suggests that maintaining an acceptable A1c level may be associated with lower treatment costs in adults with diabetes. Understanding the impact on total treatment costs of staying at the target A1c level is of great importance to managed care organizations. The goal of this study was to determine whether type 2 diabetes patients at or below the target A1c level of 7% had lower diabetes-related costs compared with patients above an A1c level of 7%. METHODS: This study was a retrospective database analysis using eligibility data, medical and pharmacy claims data, and laboratory data from a large U.S. health care organization. Patients were included in the study if they had 2 or more claims for type 2 diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 250.x0 or 250.x2) and at least 1 A1c value (first such date defined as the index date) during the 12-month period from January 1, 2002, through December 31, 2002. Patients with 2 or more medical claims for type 1 diabetes (ICD-9-CM codes 250.x1 or 250.x3) were excluded from the study. Study patients were divided into 2 groups, those at the target A1c level (7%) and those at the above-target A1c level (>7%), and were followed for a period of 1 year after their index date. Demographic, clinical, and cost variables were extracted from the administrative database. Multiple linear regression analysis was used to compare treatment costs between patients at the target A1c level and patients above target level. RESULTS: A total of 3,121 patients (46.0%) were identified as being at the target A1c level, and 3,659 patients (54%) were identified as being above the target A1c level during the study period. After controlling for confounding factors, the predicted total diabetes-related cost for the above-target group during the 1-year follow-up period was 1,540 US dollars per patient, 32% higher than the total diabetes-related cost (1,171 US dollars) for the at-target group (P <0.001). CONCLUSION: Results of this analysis suggest that managed care members with type 2 diabetes who stayed continuously at the target A1c level of 7% or less over a 1-year follow-up period incurred lower diabetes-related costs compared with managed care members with type 2 diabetes who were continuously over the target A1c level of 7%.

Adult↗

Systematic identification, classification, and characterization of the open reading frames which encode novel helicase-related proteins in Saccharomyces cerevisiae by gene disruption and Northern analysis.

Helicase-related proteins play important roles in various cellular processes incuding DNA replication, DNA repair, RNA processing and so on. It has been well known that the amino acid sequences of these proteins contain several conserved motifs, and that the open reading frames (ORFs) which encode helicase-related proteins make up several gene families. In this study, we have identified 134 ORFs that encode helicase-like proteins in the Saccharomyces genome, based on similarity with the ORFs of authentic helicase and helicase-related proteins. Multiple alignment of the ORF sequences resulted in the 134 ORFs being classified to 11 clusters. Seven out of 21 previously uncharacterized ORFs (YDL031w, YDL070w, YDL084w, YGL150c, YKL078w, YLR276c, and YMR128w) were identified by systematic gene disruption, to be essential for vegetative growth. Three (YDR332w, YGL064c, and YOL095c) out of the remaining 14 dispensable ORFs exhibited the slow-growth phenotype at 30 degrees C and 37 degrees C. Furthermore, the expression profiles of transcripts from 43 ORFs were examined under seven different growth conditions by Northern analysis and reverse transcription-polymerase chain reaction, indicating that all of the 43 tested ORFs were transcribed. Interestingly, we found that the level of transcript from 34 helicase-like genes was markedly increased by heat shock. This suggests that helicase-like genes may be involved in the biosynthesis of nucleic acids and proteins, and that the genes can be transcriptionally activated by heat shock to compensate for the repressed synthesis of mRNA and protein.

Amino Acid Sequence↗