The nature of the language input affects brain activation during learning from a natural language.

Artificial language studies have demonstrated that learners are able to segment individual word-like units from running speech using the transitional probability information. However, this skill has rarely been examined in the context of natural languages, where stimulus parameters can be quite different. In this study, two groups of English-speaking learners were exposed to Norwegian sentences over the course of three fMRI scans. One group was provided with input in which transitional probabilities predicted the presence of target words in the sentences. This group quickly learned to identify the target words and fMRI data revealed an extensive and highly dynamic learning network. These results were markedly different from activation seen for a second group of participants. This group was provided with highly similar input that was modified so that word learning based on syllable co-occurrences was not possible. These participants showed a much more restricted network. The results demonstrate that the nature of the input strongly influenced the nature of the network that learners employ to learn the properties of words in a natural language.

Duration of antibacterial treatment for uncomplicated urinary tract infection in women.

BACKGROUND: Uncomplicated urinary tract infection (UTI) is a common disease, occurring frequently in young sexually active women. In the past, seven day antibiotic therapy was recommended while the current practice is to treat uncomplicated UTI for three days. OBJECTIVES: TO compare the efficacy and safety of three-day antibiotic therapy to multi-day therapy (five days or longer) on relief of symptoms and bacteriuria at short-term and long-term follow-up. SEARCH STRATEGY: The Cochrane Library (Issue 1, 2004), the Cochrane Renal Group's Register of trials (July 2003), EMBASE (January 1980 to August 2003), and MEDLINE (January 1966 to August 2003) were searched. We scanned references of all included studies and contacted the first or corresponding author of included trials and the pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing three-days oral antibiotic therapy with multi-day therapy (five days and longer) for uncomplicated cystitis in 18 to 65 years old non-pregnant women without signs of upper UTI. DATA COLLECTION AND ANALYSIS: Data concerning bacteriological and symptomatic failure rates, occurrence of pyelonephritis and adverse effects were extracted independently by two reviewers. Relative risk (RR) and their 95% confidence intervals (CI) were estimated. Outcomes were also extracted by intention-to-treat analysis whenever possible. MAIN RESULTS: Thirty-two trials (9605 patients) were included. For symptomatic failure rates, no difference between three-day and 5-10 day antibiotic regimen was seen short-term (RR 1.06, 95% CI 0.88 to 1.28) and long-term follow-up (RR 1.09, 95% CI 0.94 to 1.27). Comparison of the bacteriological failure rates showed that three-day therapy was less effective than 5-10 day therapy for the short-term follow-up, however this difference was observed only in the subgroup of trials that used the same antibiotic in the two treatment arms (RR 1.37, 95% CI 1.07 to 1.74, P = 0.01). This difference was more significant at long-term follow-up (RR 1.43, 95% CI 1.19 to 1.73, P = 0.0002). Adverse effects were significantly more common in the 5-10 day treatment group (RR 0.83, 95% CI 0.74 to 0.93, P = 0.0010). Results were consistent for subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS: Three days of antibiotic therapy is similar to 5-10 days in achieving symptomatic cure during uncomplicated UTI treatment, while the longer treatment is more effective in obtaining bacteriological cure. In spite of the higher rate of adverse effects, treatment for 5-10 days could be considered for treatment of women in whom eradication of bacteriuria is important.

Anti-Saccharomyces cerevisiae antibodies--a novel serologic marker for Behçet's disease.

OBJECTIVE: To evaluate the prevalence and clinical correlations of antibodies against Saccharomyces cerevisiae (ASCA) among patients with BD. METHODS: Twenty-seven BD patients were studied. Data from medical files and from patients' interviews was collected, regarding the entire spectrum of disease manifestations, and a severity score was calculated for each patient. IgA- and IgG-ASCA levels, determined by ELISA, were studied in all BD patients and in three control groups: patients with recurrent aphthous stomatitis (RAS), systemic lupus erythematosus (SLE) and healthy volunteers. RESULTS: Thirteen BD patients (48.1%) were ASCA-positive, compared to one patient in each control group (10%, p = 0.01). The mean value of IgG-ASCA in the BD patients was 20.7 +/- 12.3 units, significantly higher than in patients with RAS (10.0 +/- 5.5, p < 0.001), SLE (11.8 +/- 9.3, p < 0.03) or healthy volunteers (10.8 +/- 9.8, p < 0.02). Mean IgA-ASCA level was 16.8 +/- 8.8 units in the BD patients, significantly higher compared to healthy volunteers (11.0 +/- 5.0, p = 0.02) but similar to patients with RAS (17.0 +/- 5.3). No correlation was found between ASCA and any BD-associated clinical manifestation nor the presence of HLA-B5. No difference was found in the rate of major oral ulcers nor in the systemic disease severity score between positive- and negative-ASCA patients (27.3% vs. 30.8%, and 7.31 +/- 1.80 vs. 7.28 +/- 2.27 respectively, NS). CONCLUSION: The results of our study associate, for the first time, the presence of a distinct antibody, i.e. ASCA, with BD. ASCA were not linked to a specific clinical manifestation of the disease and probably do not pose an increased risk for a more severe disease course.

Prevalence of Behçet's disease in an Arab community in Israel.

OBJECTIVE: To evaluate the prevalence of Behçet's disease (BD) in an Israeli Arab town (Taibe). METHODS: Questionnaires about the occurrence and prevalence of aphthous ulcers were distributed randomly to the parents of children attending a paediatric centre in Taibe. The parents were asked whether they or any of their children aged between 10 and 20 years had recurrent aphthous stomatitis. Any who had had more than four aphthous episodes (each episode lasting more than seven days) during the previous year were invited for an extensive interview and examination by a rheumatologist or a paediatrician. RESULTS: A total of 4876 subjects were included in this survey, of whom six (one male, five female) were diagnosed as having BD. Of these six, two were siblings (a brother and a sister). Five had skin lesions, four had visual involvement, and all had genital ulcers and joint symptoms; one in two patients had a positive pathergy test. Five of the six carried HLA-B5 antigens. The results showed a prevalence of 12/10,000 in Taibe. CONCLUSION: The prevalence of BD found in our survey is high and concurs with that found in other Mediterranean and Asian countries.

Departmental consumption of antibiotic drugs and subsequent resistance: a quantitative link.

OBJECTIVE: To look for a quantitative model linking departmental consumption of antibiotic drugs to the subsequent isolation of resistant hospital-acquired coliform pathogens. MATERIALS AND METHODS: Included in the study were all patients with hospital-acquired bloodstream infections caused by a coliform pathogen, detected in six departments of internal medicine of one university hospital during the period 1991-1996, who had not been hospitalized in the month before the infection (n = 394). Departmental consumption of antibiotics in the year before the infection [expressed as defined daily dosages (DDD)/100 patient days], antibiotic treatment given to the individual patient before the infection, the day of hospital stay on which the infection occurred, and the department and the calendar year were all included in a logistic model to predict the isolation of a resistant pathogen. We looked at five drugs: gentamicin, amikacin, cefuroxime, ceftazidime and ciprofloxacin. RESULTS: Five logistic models were fitted for the resistance to each of the antibiotic drugs. The multivariable-adjusted odds ratios for a pathogen resistant to the specific antibiotic were 1.03 [95% confidence interval (CI) 0.70-1.50] for gentamicin, 1.80 (95% CI 1.00-3.24) for amikacin, 1.12 (95% CI 1.02-1.23) for cefuroxime, 1.45 (95% CI 1.19-1.76) for ceftazidime and 1.06 (95% CI 0.57-1.97) for ciprofloxacin, per 1 DDD/100 patient days. CONCLUSIONS: The departmental consumption of cephalosporin drugs and amikacin in six autonomous departments of medicine in the same hospital was associated with a measurable and statistically significant increase in the probability of infection caused by a resistant pathogen.

Modulation of Ki67, p53 and RARbeta expression in normal, premalignant and malignant human oral epithelial cells by chemopreventive agents.

BACKGROUND: Aberrant expression of Ki67, p53 and RARbeta are characteristic of many tumor types including those of the oral cavity. Chemopreventive agents may act by modulating their expression to more normal levels. MATERIALS AND METHODS: The effects of 21 chemopreventive agents on the expression of Ki67, p53 and RARbeta were determined using a human in vitro model of normal, premalignant and malignant oral epithelial cell lines. RESULTS: Ki67 and mutant p53 (mtp53) were overexpressed in both the premalignant and malignant cell lines, whereas expression of RARbeta was high in the normal, low in the premalignant and not detectable in the malignant cell lines. Most of the agents selectively inhibited the expression of Ki67 in the premalignant and malignant cell lines. Eight of the 21 agents increased, while four agents decreased, the levels of mtp53 protein in the premalignant cell line. In the malignant cell line, five of the agents increased, while ten agents decreased mtp53 protein levels. The agents increased RARbeta expression to near normal levels in the premalignant cell line. CONCLUSION: The data suggest that the suppression of Ki67 and mtp53 are good indicators of the effectiveness of agents in premalignant and malignant oral cells, whereas the enhancement of RARbeta is a measure of effectiveness in premalignant oral cells.

Differential response of normal, premalignant and malignant human oral epithelial cells to growth inhibition by chemopreventive agents.

Squamous cell carcinoma (SCC) of the oral cavity is a multistep process, progressing through a series of discrete, irreversible and complementary alterations in genes that control cell growth, death, and differentiation. In the premalignant state, the oral mucosa progresses through various grades of epithelial dysplasia, with the potential to convert to SCC. Chemopreventive strategies are designed to suppress, reverse, or prevent the formation of premalignant lesions and their subsequent progression to SCC. In the present study, we determined the growth inhibitory effect of 21 chemopreventive agents in a cell culture model using normal, premalignant, and malignant human oral mucosal cell lines. There were significant differences in the growth inhibitory responses of these cell lines to selected retinoids and non-retinoid analogs. Among the retinoids tested, the synthetic retinamides, as a class, showed selective growth inhibition of both premalignant and malignant cells compared to normal human oral epithelial cells in culture. Within the retinamide class, 2CPR exhibited the greatest selectivity in the growth inhibition of premalignant and malignant cells. Among the non-retinoids analyzed, DFMO was a moderate to potent inhibitor of malignant and premalignant oral cell growth, respectively, and stimulated normal oral cell growth at low concentrations. Using this in vitro approach, we have identified several potential chemopreventive agents for oral cancer as selective growth inhibitors of premalignant ahd malignant human oral mucosa cells.

Changes in levels of normal ML-1 gene transcripts associated with the conversion of human nontumorigenic to tumorigenic phenotypes.

Evaluation of malignant human tumors in a xenobiotic nude mouse system has demonstrated that not all cells in tumors exhibit the capacity to form progressively growing tumors. However, nontumorigenic cells isolated from human tumors can be converted to a tumorigenic phenotype in nude mice by treatment with chemical carcinogens or by transfection with antisense to tumor suppressor genes. A newly discovered gene, designated ML-1, appears to be associated with tumorigenesis, because an ML-1 antisense cDNA construct, transfected into nontumorigenic, anchorage-independent growth (AIG) cells, was sufficient to convert these cells into a tumorigenic phenotype. The AIG cells transfected with ML-1 antisense cDNA constructs and converted to tumorigenic cells did not exhibit expression of normal ML-1 mRNA transcripts in the converted cells when evaluated by Northern analysis, whereas premalignant and normal cells expressed ML-1 transcripts at a high level. The converted cells exhibited a loss of growth control and produced tumors in a surrogate nude mouse that were greater than 2.0 cm in less than 2 months. The ML-1 gene has a DNA sequence that is 2177 bp in size and is located on chromosome number 13 on the q arm at site 12-14. Sequence analysis and investigation of GenBank sequences indicate that this is a newly described human gene.

Keratin 19 downregulation by oral squamous cell carcinoma lines increases invasive potential.

Squamous cell carcinoma (SCC) of the head and neck is the sixth most frequent cancer worldwide. The survival rate is among the lowest of the major cancers and has not improved significantly in the past two decades. Extensive local invasion and regional lymph node metastasis are, in large part, responsible for the poor clinical outcome of these tumors. Keratin intermediate filaments are the most abundant cytoskeletal proteins in SCCs and regulate the migration of normal and transformed epithelial cells. Previous studies have shown that expression of the 40-kDa keratin K19 is dysregulated in SCCs arising from oral epithelium. Immunohistochemical experiments demonstrated that, while normal epithelium and dysplastic lesions expressed abundant K19 protein, invasive SCCs exhibited a patchy or negative staining pattern. We subsequently determined that K19 expression was consistently downregulated in seven SCC lines compared with normal epithelium. We therefore wanted to determine if K19 downregulation affected the invasive phenotype of these cells. We found that SCC lines which do not express K19 are significantly more invasive in vitro than those which retain expression of this gene. Stable expression of the K19 cDNA in K19 negative cell lines altered cell morphology and intercellular adhesiveness, and significantly decreased the number of cells able to migrate through a reconstituted basement membrane. Reduced invasiveness was not due to decreased metalloproteinase activity in the K19-expressing clones. We conclude that K19 overexpression in oral SCCs decreases their invasive potential by diminishing migratory capability.

Recurrent aphthous stomatitis in Behçet's disease: clinical features and correlation with systemic disease expression and severity.

Behçet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty-five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P < 0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness.

Metastatic conversion of chemically transformed human cells.

A linear model for human cell metastasis has been developed in vitro from chemically transformed normal human cells. The chemically transformed cells are nontumorigenic in nude mice, but can be converted to a tumorigenic phenotype by transfection with a nondirectional cDNA library or antisense cDNA to the ML-1 gene. The primary transfected cell line (TR1T) forms localized, progressively growing tumors in nude mice that do not invade into the surrounding tissue. This tumorigenic TR1T cell line could be advanced into a metastatic stage following an additional transfection (TR2M cell line) with the cDNA expression library or antisense cDNA to the ML-1 gene. Metastatic cells, selected from tumors that were attached to internal organs, exhibited an increase in invasiveness as measured in vitro using an invasion chamber. The metastatic cells also exhibited an increased expression of matrix metalloproteinase-1 (MMP-1), although MMP-1 was not part of the cDNA that was transfected into either the TR1T cells or the doubly transfected metastatic TR2M cells. These data suggest that the increase in MMP-1 expression was a secondary downstream event responding to an upstream genetic change that initiated the conversion of cells from a tumorigenic to a metastatic stage. In summary, human cell lines representing premalignant, malignant, and metastatic phenotypes have been established in culture that can be used to identify gene changes that occur as normal human cells progress to a metastatic stage during tumor development. One gene, ML-1, that is found in the expression library appears to be involved in malignant progression, because ML-1 antisense cDNA will convert chemically transformed cells to both tumorigenic and metastatic stages, and cells from both local and metastatic tumors have a reduced or complete loss of expression of the ML-1 gene.

Epstein-Barr virus growth-transformed cells are converted to malignancy following transfection of a 1.3-kb CATR1 antisense construct independent of a change in the level of c-myc expression followed by a 8;14 chromosomal translocation.

The AGLCL Epstein-Barr virus (EBV) growth-transformed cell line is incapable of inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1 antisense cDNA construct, progressively growing lymphomas could be induced in nude mice. Chromosome analysis of the parental, transfected, and tumor cells revealed that a chromosomal translocation t(8;14)(q24.1;q32) had occurred in the transfected cells and was retained in cells derived from tumors. Moreover, enhanced c-myc expression, usually associated with this translocation, was either unchanged or under-expressed. These data suggest that the malignant transformation of the EBV growth-transformed cells was independent of c-myc expression and suggest that the CATR1 gene may act synergistically with the chromosomal translocation facilitating the conversion of AGLCL cells from a growth-transformed state to a malignant phenotype.

Enhanced expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase gene in human breast tumor cells.

The expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase) gene in human breast tumors was evaluated at the level of the single cell to better understand how breast tumor cells regulate expression in response to oxidative stress. Compared to normal breast ductal cells, the level of 8-oxo-dGTPase expression in the breast tumor cells increased from non-detectable levels in normal breast to expression in 30-85% of the tumor cells in individual tumors. There was no significant association between 8-oxo-dGTPase expression and tumor grade and metastatic malignancy. The upregulation of 8-oxo-dGTPase was not directly linked to the expression of cyclins D1 and D3, estrogen receptor, p53, Ki-67 and c-erbB-2, which are genes involved in cell cycle regulation and tumor growth. The elevated expression of 8-oxo-dGTPase in human breast ductal carcinoma cells appears to be a general characteristic of breast tumors and may provide the tumor cell with a cellular defense mechanism to prevent the incorporation of 8-hydroxy-deoxyguanosine during DNA replication.

Ineffectiveness of the presence of H-ras/p53 combination of mutations in squamous cell carcinoma cells to induce a conversion of a nontumorigenic to a tumorigenic phenotype.

Human tumor cells have properties in vitro or in surrogate hosts that are distinct from those of normal cells, such as immortality, anchorage independence, and tumor formation in nude mice. However, different cells from individual tumors may exhibit some, but not all of these features. In previous years, human tumor cell lines derived from different tumor and tissue types have been studied to determine those molecular changes that are associated with the in vitro properties listed above and with tumorigenicity in nude mice. In the present study, seven cell lines derived from human tumors were characterized for p53 and ras mutations that may occur in SCC tumor phenotypes and for tumor formation in nude mice. This investigation was designed to examine whether co-occurrence of mutated ras and p53 lead to a malignant stage in the progression process. None of the seven cell lines contained mutations in the recognized "hot spots" of the p53 tumor suppressor gene, but four had a nonsense/splice mutation in codon 126 and a mutation in codon 12 of the H-ras gene. The remaining three cell lines had p53 mutations in intron 5, in codon 193, and a missense mutation in codon 126, respectively. Four of seven cell lines were nontumorigenic; two of these cell lines contained a nonsense p53-126 mutation and mutated ras; one had a missense mutation at codon 126 but no mutated ras; the the fourth had only a p53 mutation at codon 193. Two of the nontumorigenic cell lines were converted to tumorigenicity after treatment with methyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine with no apparent additional mutations in either gene. Our analysis revealed that there was a high frequency of genetic diversity and mutations in both p53 and H-ras. There was also a lack of a causal relationship in the presence of mutations in p53 and the cells' ability to exhibit a malignant potential in nude mice.

Expression of molecular biomarkers in primary breast tumors implanted into a surrogate host: increased levels of cyclins correlate with tumor progression.

BACKGROUND: The overexpression or amplification of tumor suppressor and proto-oncogenes are important factors in the progression of breast cancer. Recent attention has focused on the cyclin genes, whose involvement in signal transduction pathways regulate cell cycle progression. The amplification of the cyclins D1 and D3 genes usually leads to loss of normal growth control and is thought to play an important growth regulatory role in tumor development and progression. In this report, we investigate the association of altered cyclin expression with other prognostic indicators (histological grade, lymph node status, estrogen receptor, p53, and c-erbB-2) in the progression of human breast cancer. MATERIALS AND METHODS: Surgical tumor specimens were obtained from 16 breast tubular ductal, and invasive ductal carcinomas and grafted onto gnotobiotic nude (nu/nu) mice. The expression diversity and distribution of the localization of the protein products of the c-erbB-2, cyclins D1 and D3, p53, and estrogen receptor were characterized immunohistochemically and the results in the original tumor (T0) were compared with those in the tumors that developed in nude mice (T1) xenografts. RESULTS: The T0 tumors exhibited a diversity of cellular morphology in the tumor matrix and diversity in expression of these proteins. These specific changes were also preserved in the T1 tumors. Whereas 67% of the T1 tumors exhibited high numbers of estrogen receptorpositive nuclei, only 50% of these tumors grew when grafted onto nude mice. The histological grade (14/15 were G2 to G3) and metastatic malignancy in the lymph nodes (10/15) did not appear to be related to tumor growth in the nude mouse. There was no relationship between those tumors which exhibited high percentages of c-erbB-2- and p53-positive cells and growth in nude mice. A strong association (p < 0.001) was observed between the overexpression of cyclin D1 transcripts in the T0 tumors and the continued growth of the T1 tumors in nude mice. In the T1 tumors, both cyclins D1 and D3, estrogen receptor, and p53 were observed in 49% to 86% of the cells of the T1 tumors examined; the number of cells expressing c-erbB-2 protein varied widely in these tumors. CONCLUSIONS: The results indicate that the tumor matrix exhibits a diversity in the level of phenotypic expression of genes involved in cellular growth of breast tumors in both the T0 or T1 host environment. Changes in cyclin activity appear to correlate with the vigorous level of breast tumor growth and progression.

The effect of an angiotensin converting enzyme inhibitor on skin microvascular hyperaemia in microalbuminuric insulin-dependent diabetes mellitus.

Patients with longstanding insulin-dependent (Type 1) diabetes mellitus (IDDM) are reported to have microvascular complications in most capillary beds. The microvascular hyperaemia of the skin in normoalbuminuric and microalbuminuric IDDM patients and healthy volunteers was measured with laser Doppler flowmetry. The effect of 3 and 9 months of treatment with captopril, an angiotensin converting enzyme inhibitor, on hyperaemia in the microalbuminuric patients was studied. Mean (+/- SD) pretreatment duration of skin postocclusive reactive hyperaemia was longer in microalbuminuric than in both normoalbuminuric patients and healthy volunteers (118.2 +/- 34.4 vs 57.8 +/- 16.0 vs 63.3 +/- 18.3 sec, respectively, p < 0.00001). After 3 and 9 months of captopril treatment the prolonged hyperaemia was shortened to 78.6 +/- 45.6 s (p < 0.01) and 62.3 +/- 55.6 s (p < 0.03), respectively. Urinary albumin excretion decreased from 63.9 +/- 43.5 to 33.4 +/- 28.1 mg 24 h-1 at 3 months treatment (p < 0.002) and 43.1 +/- 38.5 mg 24 h-1 at the end of the study period (p < 0.02). A positive correlation between changes in urinary albumin excretion and the shortening of the skin postocculsive reactive hyperaemia was found. Blood pressure remained in the same range throughout. These results show that captopril affects skin blood flow, independent of its hypotensive effect. This action may reflect the influence of angiotensin converting enzyme inhibitor on vascular beds other than those of the kidneys.

Improving empirical antibiotic treatment: prospective, nonintervention testing of a decision support system.

OBJECTIVES: Develop a problem-orientated and data-based decision support system (DSS) to improve empirical antibiotic treatment, and compare the performance of the system to that of the physician. DESIGN: The DSS was tested in a prospective, noninterventional, comparative cohort study. SETTING: University hospital in Israel. SUBJECTS: Consecutive patients (n = 496) in four departments of internal medicine suspected of harboring a moderate to severe bacterial infection. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The percentage of appropriate empirical antibiotic treatments. RESULTS: Out of 496 patients included in the study, 219 had positive cultures or serological tests. The physicians prescribed inappropriate empirical antibiotic treatment in 91 of 219 patients (42%); whilst the recommendations of the system were inappropriate in 50 patients (23%) (P < 0.05). Superfluous treatment was prescribed in 15% of patients by the physician, and in 11% by the system. Out of the 91 patients given inappropriate treatment by the physician, the DSS advised treatment to which the pathogens were susceptible in 61 patients. The advantage of the DSS over the physician was most evident in multiresistant gram-negative isolates, enterococci and Staphylococcus aureus. Out of the 277 patients with negative cultures, the DSS advised narrower-spectrum antibiotic treatment than prescribed by the physicians in 27% of patients, and broader-spectrum in 13%. CONCLUSION: A problem-orientated, data-based DSS outperformed physicians in the choice of appropriate empirical antibiotic treatment, and recommended less broad-spectrum antibiotics.

Malignant conversion of human cells by antisense cDNA to a putative tumor suppressor gene.

A cell line, SCC83-01-82, derived from a human oral squamous carcinoma, was non-tumorigenic in nude mice, a characteristic of premalignant cells. Conversion of these cells to a tumorigenic phenotype with chemical mutagens did not increase mutations in hot spots or other conserved regions of p53 or H-ras genes. Investigation of the tumorigenic conversion using an expression library resulted in isolation of a previously unidentified gene, CATR1, located on the long arm of chromosome 7 at band approximately q31-32. Evidence for the involvement of this gene in conversion to tumorigenicity was demonstrated by introduction of a eukaryotic expression CATR1 construct into SCC83-01-82 cells. Transfection with the antisense construct reduced the expression of CATR1 in tumors formed by the transfected cells, suggesting that the antisense suppression of endogenous CATR1 expression appeared to be sufficient for tumorigenic conversion. These results are consistent with previous reports of cytogenetic analyses of tumors, that 7q31-32 contains a gene(s) with tumor suppressor activity; CATR1 is a candidate for this putative suppressor gene.