bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of diabetes mellitus on the spectrum of uropathogens and the antimicrobial resistance in elderly adult patients with urinary tract infection
Authors: Bonadio Mario , Costarelli Silvia , Morelli Giovanna , Tartaglia Tiziana
Published: April 2006

Background

The role of Diabetes mellitus (DM) in the etiology and in the antimicrobial resistance of uropathogens in patients with urinary tract infection has not been well clarified. For this reason we have evaluated the spectrum of uropathogens and the profile of antibiotic resistance in both diabetic and non diabetic patients with asymptomatic urinary tract infection (UTI).

Methods

Urinary isolates and their patterns of susceptibility to the antimicrobials were evaluated in 346 diabetics (229 females and 117 males) and 975 non diabetics (679 females and 296 males) who were screened for significant bacteriuria (≥105 CFU/mL urine). The mean age of diabetic and non diabetic patients was respectively 73.7 yrs ± 15 S.D. and 72.7 ± 24 (p = NS).

Results

Most of our patients had asymptomatic UTI. The most frequent causative organisms of bacteriuria in females with and without DM were respectively : E. coli 54.1% vs 58.2% (p = NS), Enterococcus spp 8.3% vs 6.5% (p = NS), Pseudomonas spp 3.9 vs 4.7% (p = NS). The most frequent organisms in diabetic and non diabetic males were respectively E. coli 32.5% vs 31.4% (p = NS), Enterococcus spp 9.4% vs 14.5% (p = NS), Pseudomonas spp 8.5% vs 17.2% (p = <0.02). A similar isolation rate of E. coli, Enterococcus spp and Pseudomonas spp was also observed in patients with indwelling bladder catheter with and without DM. No significant differences in resistance rates to ampicillin, nitrofurantoin, cotrimoxazole and ciprofloxacin of E. coli and Enteroccus spp were observed between diabetic and non diabetic patients.

Conclusion

In our series of patients with asymptomatic UTI (mostly hospital acquired), diabetes mellitus per se does not seem to influence the isolation rate of different uropathogens and their susceptibility patterns to antimicrobials.
Identification of polymorphisms and balancing selection in the male infertility candidate gene, ornithine decarboxylase antizyme 3
Authors: Christensen Greg L , Ivanov Ivaylo P , Wooding Stephen P , Atkins John F , Mielnik Anna , Schlegel Peter N , Carrell Douglas T
Published: April 2006

Background

The antizyme family is a group of small proteins that play a role in cell growth and division by regulating the biosynthesis of polyamines (putrescine, spermidine, spermine). Antizymes regulate polyamine levels primarily through binding ornithine decarboxylase (ODC), an enzyme key to polyamine production, and targeting ODC for destruction by the 26S proteosome. Ornithine decarboxylase antizyme 3 (OAZ3) is a testis-specific antizyme paralog and the only antizyme expressed in the mid to late stages of spermatogenesis.

Methods

To see if mutations in the OAZ3 gene are responsible for some cases of male infertility, we sequenced and evaluated the genomic DNA of 192 infertile men, 48 men of known paternity, and 34 African aborigines from the Mbuti tribe in the Democratic Republic of the Congo. The coding sequence of OAZ3 was further screened for polymorphisms by SSCP analysis in the infertile group and an additional 250 general population controls. Identified polymorphisms in the OAZ3 gene were further subjected to a haplotype analysis using PHASE 2.02 and Arlequin 2.0 software programs.

Results

A total of 23 polymorphisms were identified in the promoter, exons or intronic regions of OAZ3. The majority of these fell within a region of less than two kilobases. Two of the polymorphisms, -239 A/G in the promoter and 4280 C/T, a missense polymorphism in exon 5, may show evidence of association with male infertility. Haplotype analysis identified 15 different haplotypes, which can be separated into two divergent clusters.

Conclusion

Mutations in the OAZ3 gene are not a common cause of male infertility. However, the presence of the two divergent haplotypes at high frequencies in all three of our subsamples (infertile, control, African) suggests that they have been maintained in the genome by balancing selection, which was supported by a test of Tajima's D statistic. Evidence for natural selection in this region implies that these haplotypes may be associated with a trait other than infertility. This trait may be related to another function of OAZ3 or a region in tight linkage disequilibrium to the gene.
Paraoxonase gene polymorphisms and haplotype analysis in a stroke population
Authors: Pasdar Alireza , Ross-Adams Helen , Cumming Alastair , Cheung John , Whalley Lawrence , St Clair David , MacLeod Mary-Joan
Published: April 2006

Background

Paraoxonase (PON) has anti-atherogenic activity due to its protective function against low density lipoprotein (LDL) oxidation. Alteration of enzyme activity due to polymorphisms in the PON genes may influence the development of atheroma and thus affect stroke risk. Three PON genes (PON1, PON2 and PON3) have been identifiedand mapped to chromosome 7.

Methods

We looked at the distribution of paraoxonase polymorphisms and haplotype arrangement in 397 Caucasian ischaemic stroke patients and 405 controls. We investigated 6 different common single nucleotide polymorphisms (SNP) in PON genes; two substitutions in PON1 ["A/G": Gln (Q)/Arg (R)] at codon 192 and ["T/A": Leu (L)/Met (M)] at codon 55, two in PON2 at codon 311 ["G/A": Cys (C)/Ser (S)] and codon 148 ["C/G": Ala (A)/Gly (G)] and two SNPs, both "A" to "G" substitutions, in PON3 – intronic rs2074353, which we designated PON3-1 and [Ala (A)/Ala (A)] at codon 99, designated as PON3-3. Dynamic Allele Specific Hybridisation (DASH) was used as the genotyping assay. Haplotype analysis was performed using both PHASE and EHPLUS programs.

Results

Genotype and allele frequencies were similar in cases and controls. Lipid profiles were not influenced by PON genotype. Haplotype frequencies for the six loci (PON2-148, PON2-311, PON3-3, PON3-1, PON1-55 and PON1-192) were estimated. Comparison of the two programs showed a significant difference in haplotype arrangements with EHPLUS (p-value = 0.005) but not with PHASE Ver.2 (p-value = 0.12). The 112211 (1 = frequent allele, 2 = rare allele) haplotype arrangement was commoner in cases than controls (p = 0.015), and the 111121 haplotype was commoner in controls (p = 0.006).

Conclusion

Our study did not identify a role for individual paraoxonase gene polymorphisms in the pathogenesis of ischaemic stroke. Findings of haplotype differences should be confirmed in large scale studies. The importance of using a well-validated haplotype analysis program is also underlined.
Transgenic mice with mammary gland targeted expression of human cortactin do not develop (pre-malignant) breast tumors: studies in MMTV-cortactin and MMTV-cortactin/-cyclin D1 bitransgenic mice
Authors: van Rossum Agnes GSH , van Bragt Maaike PA , Schuuring-Scholtes Ellen , van der Ploeg Jan CM , van Krieken Johan HJM , Kluin Philip M , Schuuring Ed
Published: April 2006

Background

In human breast cancers, amplification of chromosome 11q13 correlates with lymph node metastasis and increased mortality. To date, two genes located within this amplicon, CCND1 and EMS1, were considered to act as oncogenes, because overexpression of both proteins, respectively cyclin D1 and cortactin, correlated well with 11q13 amplification. Cyclin D1 is involved in cell cycle regulation and the F-actin-binding protein cortactin in cytoskeletal dynamics and cell migration. To study the role of cortactin in mammary gland tumorigenesis, we examined mouse mammary tumor virus (MMTV)-cortactin transgenic mice and MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice.

Methods

MMTV-cortactin transgenic mice were generated and intercrossed with previously described MMTV-cyclin D1 transgenic mice. Immunohistochemical, Northern and Western blot analyses were performed to study the expression of human transgene cortactin during mammary gland development and in mammary tumors. For tumor incidence studies, forced-bred, multiparous mice were used to enhance transgene expression in the mammary gland. Microscopical examination was performed using haematoxylin and eosin staining.

Results

Mammary gland tumors arose stochastically (incidence 21%) with a mean age of onset at 100 weeks. This incidence, however, did not exceed that of aged-matched control FVB/N mice (38%), which unexpectedly, also developed spontaneous mammary gland tumors. We mimicked 11q13 amplification by generating MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice but did not observe any synergistic effect of cortactin on cyclin D1-induced mammary hyperplasias or carcinomas, nor development of distant metastasis.

Conclusion

From this study, we conclude that development of (pre-malignant) breast tumors in either wild type or MMTV-cyclin D1 mice was not augmented due to mammary gland targeted overexpression of human cortactin.
Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer
Authors: Ananthanarayanan Vijayalakshmi , Deaton Ryan J , Yang Ximing J , Pins Michael R , Gann Peter H
Published: April 2006

Background

Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant.

Methods

The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered "near" and "far", respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately.

Results

Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. "Near" normal glands had higher Mcm-2 indices compared to "far" glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend across compartments or evidence for field effects.

Conclusion

These results demonstrate that proliferation and apoptosis are altered not only in preneoplastic lesions but also in apparently normal looking epithelium associated with cancer. Luminal cell expression of Mcm-2 appears to be particularly promising as a marker of high-risk normal epithelium. The role of apoptotic markers such as activated caspase-3 is more complex, and might depend on the proliferation status of the tissue in question.
Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers
Authors: Copson Ellen R , White Helen E , Blaydes Jeremy P , Robinson David O , Johnson Peter W , Eccles Diana M
Published: April 2006

Background

The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.

Methods

Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus.

Results

The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80).

Conclusion

We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.
The dimensions of responsiveness of a health system: a Taiwanese perspective
Authors: Hsu Chih-Cheng , Chen Likwang , Hu Yu-Whuei , Yip Winnie , Shu Chen-Chun
Published: April 2006

Background

Responsiveness is an indicator used to measure how well a health system performs relative to non-health aspects. This study assessed whether seven dimensions proposed by the World Health Organization (WHO) to measure responsiveness (dignity, autonomy, confidentiality, prompt attention, social support, basic amenities, and choices of providers) are applicable in evaluating the health system of Taiwan.

Methods

A key informant survey and focus group research were used in this study. The translated WHO proposed questionnaire was sent to 205 nominated key informants by mail, and 132 (64.4%) were returned. We used principal component analysis to extract factors. Linear regression analysis was used to assess the relationship between the total score and the extracted factors. A qualitative content analysis was also carried out in focus group research.

Results

Principal component analysis produced five factors (respect, access, confidentiality, basic amenities, and social support) that explained 63.5% of the total variances. These five factors demonstrated acceptable internal consistency and four of them (except social support) were significantly correlated with the total responsiveness score. The focus group interviews revealed health providers' communication ability and medical ethics were also highly appraised by Taiwanese.

Conclusion

When the performance of a health system is to be evaluated, elements of responsiveness proposed by WHO may have to be tailored to fit different cultural backgrounds. Four key features illustrate the uniqueness of Taiwanese perspectives: the idea of autonomy may not be conceptualized, prompt attention and choice of providers are on the same track, social support during care is trivially correlated to the total responsiveness score, and accountability of health providers is deemed essential to a health system.
Vietnam military service history and prostate cancer
Authors: Leavy Justine , Ambrosini Gina , Fritschi Lin
Published: April 2006

Background

Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study.

Methods

Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service.

Results

Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06). An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00) or brothers (OR = 2.05; 95% CI 1.20–3.50) diagnosed with prostate cancer.

Conclusion

These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer.
The impact of fathers' physical and psychosocial work conditions on attempted and completed suicide among their children
Authors: Aleck Ostry , Stefania Maggi , James Tansey , James Dunn , Ruth Hershler , Lisa Chen , Amber Louie , Clyde Hertzman
Published: April 2006

Background

Adverse employment experiences, particularly exposure to unemployment and the threat of unemployment, have been strongly associated with several adverse mental and physical health outcomes including suicide. However, virtually no research has been conducted on the trans-generational impact of parental working conditions on attempted or completed suicide among their children.

Methods

We conducted a nested case control study based on a cohort, gathered in the western Canadian province of British Columbia, of male sawmill workers and a second cohort of their children. Physical and psychosocial work conditions to which fathers were exposed during the first 16 years of their children's lives, measured using the demand/control model, were linked to hospital suicide records (attempted and completed) among their children.

Results

Two hundred and fifty children in the cohort attempted or committed suicide between 1985 and 2001. Multivariate models, with partial control for father's mental health outcomes prior to their child's suicide demonstrate, 1) a strong association between low duration of father's employment at a study sawmill and attempted suicide for their male children, 2) elevated odds for attempted suicide among female children of fathers' employed in a sawmill job with low control and, 3) a strong association between fathers in jobs with low psychological demand and completed suicides among male children.

Conclusion

Exposure of fathers to adverse psychosocial work conditions during the first 16 years of their children's life was associated with greater odds for attempted and completed suicide among their children.
Coexistence between renal cell cancer and Hodgkin's lymphoma: A rare coincidence
Authors: Jimenez I Victor H
Published: April 2006

Background

Renal cell carcinoma is the most common kidney tumor in adults and accounts for approximately 3% of adult malignancies. An increased incidence of second malignancies has been well documented in a number of different disorders, such as head and neck tumors, and hairy cell leukemia. In addition, treatment associated second malignancies (usually leukemias and lymphomas but also solid tumors) have been described in long term survivors of Hodgkin's lymphoma (HL), Non Hodgkin's lymphoma and in various pediatric tumors.

Case presentation

We present the case of a 66 year-old woman with abdominal pain and dyspnea. We performed a thorax CT scan that showed lymph nodes enlargement and subsequently by presence of abdominal pain was performed an abdominal and pelvis CT scan that showed a right kidney tumor of 4 × 5 cms besides of abdominal lymph nodes enlargement. A radical right nephrectomy was designed and Hodgkin's lymphoma was diagnosed in the abdominal lymph nodes while renal cell tumor exhibited a renal cell cancer. Patient received EVA protocol achieving complete response.

Conclusion

We described the first case reported in the medical literature of the coexistence between Hodgkin's lymphoma and renal cell cancer. Previous reports have shown the relationship of lymphoid neoplasms with solid tumors, but they have usually described secondary forms of cancer related to chemotherapy.
Increasing incidence of skin disorders in children? A comparison between 1987 and 2001
Authors: Mohammedamin Robbert SA , van der Wouden Johannes C , Koning Sander , van der Linden Michiel W , Schellevis François G , van Suijlekom-Smit Lisette WA , Koes Bart W
Published: April 2006

Background

The increasing proportion of skin diseases encountered in general practice represents a substantial part of morbidity in children. Only limited information is available about the frequency of specific skin diseases. We aimed to compare incidence rates of skin diseases in children in general practice between 1987 and 2001.

Methods

We used data on all children aged 0–17 years derived from two consecutive surveys performed in Dutch general practice in 1987 and 2001. Both surveys concerned a longitudinal registration of GP consultations over 12 months. Each disease episode was coded according to the International Classification of Primary Care. Incidence rates of separate skin diseases were calculated by dividing all new episodes for each distinct ICPC code by the average study population at risk. Data were stratified for socio-demographic characteristics.

Results

The incidence rate of all skin diseases combined in general practice decreased between 1987 and 2001. Among infants the incidence rate increased. Girls presented more skin diseases to the GP. In the southern part of the Netherlands children consulted their GP more often for skin diseases compared to the northern part. Children of non-Western immigrants presented relatively more skin diseases to the GP. In general practice incidence rates of specific skin diseases such as impetigo, dermatophytosis and atopic dermatitis increased in 2001, whereas warts, contact dermatitis and skin injuries decreased.

Conclusion

The overall incidence rate of all skin diseases combined in general practice decreased whereas the incidence rates of bacterial, mycotic and atopic skin diseases increased.
Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli
Authors: Watts Kevin T , Lee Pyung C , Schmidt-Dannert Claudia
Published: April 2006

Background

Phenylpropanoids are the precursors to a range of important plant metabolites such as the cell wall constituent lignin and the secondary metabolites belonging to the flavonoid/stilbene class of compounds. The latter class of plant natural products has been shown to function in a wide range of biological activities. During the last few years an increasing number of health benefits have been associated with these compounds. In particular, they demonstrate potent antioxidant activity and the ability to selectively inhibit certain tyrosine kinases. Biosynthesis of many medicinally important plant secondary metabolites, including stilbenes, is frequently not very well understood and under tight spatial and temporal control, limiting their availability from plant sources. As an alternative, we sought to develop an approach for the biosynthesis of diverse stilbenes by engineered recombinant microbial cells.

Results

A pathway for stilbene biosynthesis was constructed in Escherichia coli with 4-coumaroyl CoA ligase 1 4CL1) from Arabidopsis thaliana and stilbene synthase (STS) cloned from Arachis hypogaea. E. coli cultures expressing these enzymes together converted the phenylpropionic acid precursor 4-coumaric acid, added to the growth medium, to the stilbene resveratrol (>100 mg/L). Caffeic acid, added in the same way, resulted in the production of the expected dihydroxylated stilbene, piceatannol (>10 mg/L). Ferulic acid, however, was not converted to the expected stilbene product, isorhapontigenin. Substitution of 4CL1 with a homologous enzyme, 4CL4, with a preference for ferulic acid over 4-coumaric acid, had no effect on the conversion of ferulic acid. Accumulation of tri- and tetraketide lactones from ferulic acid, regardless of the CoA-ligase expressed in E. coli, suggests that STS cannot properly accommodate and fold the tetraketide intermediate to the corresponding stilbene structure.

Conclusion

Phenylpropionic acids, such as 4-coumaric acid and caffeic acid, can be efficiently converted to stilbene compounds by recombinant E. coli cells expressing plant biosynthetic genes. Optimization of precursor conversion and cyclization of the bulky ferulic acid precursor by host metabolic engineering and protein engineering may afford the synthesis of even more structurally diverse stilbene compounds.
Female genital mutilation of a karyotypic male presenting as a female with delayed puberty
Authors: Ellaithi M , Nilsson T , Gisselsson D , Elagib A , Eltigani H , Fadl-Elmula I
Published: April 2006

Background

Female genital mutilation (FGM) is commonly practiced mainly in a belt reaching from East to West Africa north of the equator. The practice is known across socio-economic classes and among different ethnic, religious, and cultural groups. Few studies have been appropriately designed to measure the health effects of FGM. However, the outcome of FGM on intersex individuals has never been discussed before.

Case presentation

The patient first presented as a female with delayed puberty. Hormonal analysis revealed a normal serum prolactin level of 215 Mu/L, a low FSH of 0.5 Mu/L, and a low LH of 1.1 Mu/L. Type IV FGM (Pharaonic circumcision) had been performed during childhood. Chromosomal analysis showed a 46, XY karyotype and ultrasonography verified a soft tissue structure in the position of the prostate.

Conclusion

FGM pose a threat to the diagnosis and management of children with abnormal genital development in the Sudan and similar societies.
Community wide electronic distribution of summary health care utilization data
Authors: Lagoe Ronald J , Westert Gert P
Published: April 2006

Background

In recent years, the use of digital technology has supported widespread sharing of electronic health care data. Although this approach holds considerable promise, it promises to be a complicated and expensive undertaking. This study described the development and implementation of a community wide system for electronic sharing of summary health care utilization data.

Methods

The development of the community wide data system focused on the following objectives: ongoing monitoring of the health care system, evaluation of community wide individual provider initiatives, identification and development of new initiatives.

The system focused on the sharing of data related to hospital acute care, emergency medical services, long term care, and mental health. It was based on the daily distribution of reports among all health care providers related to these services.

Results

The development of the summary reports concerning health care utilization produced a system wide view of health care in Syracuse, New York on a daily basis. It was not possible to isolate the results of these reports because of the impact of specific projects and other factors. At the same time, the reports were associated with reduction of hospital inpatient stays, improvement of access to hospital emergency departments, reductions in stays for patients discharged to nursing homes, and increased access of mental health patients to hospital inpatient units.

Conclusion

The implementation of the system demonstrated that summary electronic utilization data could provide daily information that would support the improvement of health care outcomes and efficiency. This approach could be implemented in a simple, direct manner with minimal expenses.
Impact of treatment policies on patient outcomes and resource utilization in acute cholecystitis in Japanese hospitals
Authors: Sekimoto Miho , Imanaka Yuichi , Hirose Masahiro , Ishizaki Tatsuro , Murakami Genki , Fukata Yushi ,   QIP Cholecystectomy Expert Group
Published: April 2006

Background

Although currently available evidence predominantly recommends early laparoscopic cholecystectomy (LC) for the treatment of acute cholecystitis, this strategy has not been widely adopted in Japan. Herein, we describe a hospital-based study of patients with acute cholecystitis in 9 Japanese teaching hospitals in order to evaluate the impact of different institutional strategies in treating acute cholecystitis on overall patient outcomes and medical resource utilization.

Methods

From an administrative database and chart review, we identified 228 patients diagnosed with acute cholecystitis who underwent cholecystectomy between April 2001 and June 2003. In order to examine the relationship between hospitals' propensity to perform LC and patient outcomes and/or medical resource utilization, we divided the hospitals into three groups according to the observed to expected ratio of performing LC (LC propensity), and compared the postoperative complication rate, length of hospitalization (LOS), and medical charges.

Results

No hospital adopted the policy of early surgery, and the mean overall LOS among the subjects was 30.9 days. The use of laparoscopic surgery varied widely across the hospitals; the adjusted rates of LC to total cholecystectomies ranged from 9.5% to 77%. Although intra-operative complication rate was significantly higher among patients whom LC was initially attempted when compared to those whom OC was initially attempted (9.7% vs. 0%), there was no significant association between LC propensity and postoperative complication rates. Although the postoperative time to oral intake and postoperative LOS was significantly shorter in hospitals with high use of LC, the overall LOS did not differ among hospital groups with different LC propensities. Medical charges were not associated with LC propensity.

Conclusion

Under the prevailing policy of delayed surgery, in terms of the postoperative complication rate and medical resource utilization, our study did not show the superiority of LC in treating acute cholecystitis patients. The timing of surgery and discharge was mainly determined by the institutional policy in Japan, rather than by the clinical course of the patient; however, considering the substantially less postoperative pain and shorter recovery time of LC compared to OC, LC should be actively applied for the treatment of acute cholecystitis. If the policy of early surgery were universally applied, the advantage of LC over OC may be more clearly demonstrated.
Applications of cell sorting in biotechnology
Authors: Mattanovich Diethard , Borth Nicole
Published: April 2006

Due to its unique capability to analyze a large number of single cells for several parameters simultaneously, flow cytometry has changed our understanding of the behavior of cells in culture and of the population dynamics even of clonal populations. The potential of this method for biotechnological research, which is based on populations of living cells, was soon appreciated. Sorting applications, however, are still less frequent than one would expect with regard to their potential. This review highlights important contributions where flow cytometric cell sorting was used for physiological research, protein engineering, cell engineering, specifically emphasizing selection of overproducing cell lines. Finally conclusions are drawn concerning the impact of cell sorting on inverse metabolic engineering and systems biology.
Heterologous expression of Brucella abortus GroEL heat-shock protein in Lactococcus lactis
Authors: Miyoshi Anderson , Bermúdez-Humarán Luis G , Ribeiro Luciana A , Le Loir Yves , Oliveira Sérgio C , Langella Philippe , Azevedo Vasco
Published: April 2006

Background

Brucella abortusis a facultative intracellular pathogen that mainly infects cattle and humans. Current vaccines rely on live attenuated strains ofB. abortus, which can revert to their pathogenic status and thus are not totally safe for use in humans. Therefore, the development of mucosal live vaccines using the food-grade lactic acid bacterium,Lactococcus lactis, as an antigen delivery vector, is an attractive alternative and a safer vaccination strategy againstB. abortus. Here, we report the construction ofL. lactisstrains genetically modified to produceB. abortusGroEL heat-shock protein, a candidate antigen, in two cellular locations, intracellular or secreted.

Results

Only the secreted form of GroEL was stably produced inL. lactis, suggesting a detrimental effect of GroEL protein when intracellularly produced in this bacterium. Only trace amounts of mature GroEL were detected in the supernatant fraction of induced lactococcal cultures, and the GroEL precursor remained stacked in the cell fraction. Attempts to raise the secretion yields were made, but even when GroEL was fused to a synthetic propeptide, secretion of this antigen was not improved.

Conclusion

We found thatL. lactisis able to produce, and to secrete, a stable form of GroEL into the extracellular medium. Despite the low secretion efficiency of GroEL, which suggest that this antigen interacts with the cell envelope ofL. lactis, secretion seems to be the best way to achieve both production and protein yields, regardless of cellular location. TheL. lactisstrain secreting GroEL has potential forin vivoimmunization.
Coordinate regulation of fibronectin matrix assembly by the plasminogen activator system and vitronectin in human osteosarcoma cells
Authors: Vial Daniel , Monaghan-Benson Elizabeth , McKeown-Longo Paula J
Published: April 2006

Background

Plasminogen activators are known to play a key role in the remodeling of bone matrix which occurs during tumor progression, bone metastasis and bone growth. Dysfunctional remodeling of bone matrix gives rise to the osteoblastic and osteolytic lesions seen in association with metastatic cancers. The molecular mechanisms responsible for the development of these lesions are not well understood. Studies were undertaken to address the role of the plasminogen activator system in the regulation of fibronectin matrix assembly in the osteoblast-like cell line, MG-63.

Results

Treatment of MG-63 cells with P25, a peptide ligand for uPAR, resulted in an increase in assembly of fibronectin matrix which was associated with an increase in the number of activated β1 integrins on the cell surface. Overexpression of uPAR in MG-63 cells increased the effect of P25 on fibronectin matrix assembly and β1 integrin activation. P25 had no effect on uPAR null fibroblasts, confirming a role for uPAR in this process. The addition of plasminogen activator inhibitor Type I (PAI-1) to cells increased the P25-induced fibronectin polymerization, as well as the number of activated integrins. This positive regulation of PAI-1 on fibronectin assembly was independent of PAI-1's anti-proteinase activity, but acted through PAI-1 binding to the somatomedin B domain of vitronectin.

Conclusion

These results indicate that vitronectin modulates fibronectin matrix assembly in osteosarcoma cells through a novel mechanism involving cross-talk through the plasminogen activator system.
The distribution of hatching time in Anopheles gambiae
Authors: Yaro Alpha S , Dao Adama , Adamou Abdoulaye , Crawford Jacob E , Ribeiro José MC , Gwadz Robert , Traoré Sekou F , Lehmann Tovi
Published: April 2006

Background

Knowledge of the ecological differences between the molecular forms of Anopheles gambiae and their sibling species, An. arabiensis might lead to understanding their unique contribution to disease transmission and to better vector control as well as to understanding the evolutionary forces that have separated them.

Methods

The distributions of hatching time of eggs of wild An. gambiae and An. arabiensis females were compared in different water types. Early and late hatchers of the S molecular form were compared with respect to their total protein content, sex ratio, development success, developmental time and adult body size.

Results

Overall, the distribution of hatching time was strongly skewed to the right, with 89% of the eggs hatching during the second and third day post oviposition, 10% hatching during the next four days and the remaining 1% hatching over the subsequent week. Slight, but significant differences were found between species and between the molecular forms in all water types. Differences in hatching time distribution were also found among water types (in each species and molecular form), suggesting that the eggs change their hatching time in response to chemical factors in the water. Early hatchers were similar to late hatchers except that they developed faster and produced smaller adults than late hatchers.

Conclusion

Differences in hatching time and speed of development among eggs of the same batch may be adaptive if catastrophic events such as larval site desiccation are not rare and the site's quality is unpredictable. The egg is not passive and its hatching time depends on water factors. Differences in hatching time between species and molecular forms were slight, probably reflecting that conditions in their larval sites are rather similar.
Movies of cellular and sub-cellular motion by digital holographic microscopy
Authors: Mann Christopher J , Yu Lingfeng , Kim Myung K
Published: April 2006

Background

Many biological specimens, such as living cells and their intracellular components, often exhibit very little amplitude contrast, making it difficult for conventional bright field microscopes to distinguish them from their surroundings. To overcome this problem phase contrast techniques such as Zernike, Normarsky and dark-field microscopies have been developed to improve specimen visibility without chemically or physically altering them by the process of staining. These techniques have proven to be invaluable tools for studying living cells and furthering scientific understanding of fundamental cellular processes such as mitosis. However a drawback of these techniques is that direct quantitative phase imaging is not possible. Quantitative phase imaging is important because it enables determination of either the refractive index or optical thickness variations from the measured optical path length with sub-wavelength accuracy.

Digital holography is an emergent phase contrast technique that offers an excellent approach in obtaining both qualitative and quantitative phase information from the hologram. A CCD camera is used to record a hologram onto a computer and numerical methods are subsequently applied to reconstruct the hologram to enable direct access to both phase and amplitude information. Another attractive feature of digital holography is the ability to focus on multiple focal planes from a single hologram, emulating the focusing control of a conventional microscope.

Methods

A modified Mach-Zender off-axis setup in transmission is used to record and reconstruct a number of holographic amplitude and phase images of cellular and sub-cellular features.

Results

Both cellular and sub-cellular features are imaged with sub-micron, diffraction-limited resolution. Movies of holographic amplitude and phase images of living microbes and cells are created from a series of holograms and reconstructed with numerically adjustable focus, so that the moving object can be accurately tracked with a reconstruction rate of 300ms for each hologram. The holographic movies show paramecium swimming among other microbes as well as displaying some of their intracellular processes. A time lapse movie is also shown for fibroblast cells in the process of migration.

Conclusion

Digital holography and movies of digital holography are seen to be useful new tools for visualization of dynamic processes in biological microscopy. Phase imaging digital holography is a promising technique in terms of the lack of coherent noise and the precision with which the optical thickness of a sample can be profiled, which can lead to images with an axial resolution of a few nanometres.
Dominant negative retinoic acid receptor initiates tumor formation in mice
Authors: Kupumbati Tara S , Cattoretti Giorgio , Marzan Christine , Farias Eduardo F , Taneja Reshma , Mira-y-Lopez Rafael
Published: April 2006

Background

Retinoic acid suppresses cell growth and promotes cell differentiation, and pharmacological retinoic acid receptor (RAR) activation is anti-tumorigenic. This begs the question of whether chronic physiological RAR activation by endogenous retinoids is likewise anti-tumorigenic.

Results

To address this question, we generated transgenic mice in which expression of a ligand binding defective dominant negative RARα (RARαG303E) was under the control of the mouse mammary tumor virus (MMTV) promoter. The transgene was expressed in the lymphoid compartment and in the mammary epithelium. Observation of aging mice revealed that transgenic mice, unlike their wild type littermates, developed B cell lymphomas at high penetrance, with a median latency of 40 weeks. MMTV-RARαG303E lymphomas were high grade Pax-5+, surface H+L Ig negative, CD69+ and BCL6- and cytologically and phenotypically resembled human adult high grade (Burkitt's or lymphoblastic) lymphomas. We postulated that mammary tumors might arise after a long latency period as seen in other transgenic models of breast cancer. We tested this idea by transplanting transgenic epithelium into the cleared fat pads of wild type hosts, thus bypassing lymphomagenesis. At 17 months post-transplantation, a metastatic mammary adenocarcinoma developed in one of four transplanted glands whereas no tumors developed in sixteen of sixteen endogenous glands with wild type epithelium.

Conclusion

These findings suggest that physiological RAR activity may normally suppress B lymphocyte and mammary epithelial cell growth and that global RAR inactivation is sufficient to initiate a stochastic process of tumor development requiring multiple transforming events. Our work makes available to the research community a new animal resource that should prove useful as an experimental model of aggressive sporadic lymphoma in immunologically uncompromised hosts. We anticipate that it may also prove useful as a model of breast cancer.
Prognostic significance of new onset ascites in patients with pancreatic cancer
Authors: Zervos Emmanuel E , Osborne Dana , Boe Brian A , Luzardo German , Goldin Steven B , Rosemurgy Alexander S
Published: April 2006

Background

The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer.

Methods

A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined.

Results

A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III) underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm). All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm) presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after.

Conclusion

Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.
Ten year survival after excision of squamous cell cancer in Zenker's diverticulum: report of a case
Authors: Dionigi Gianlorenzo , Sessa Fausto , Rovera Francesca , Boni Luigi , Carrafiello Gianpaolo , Dionigi Renzo
Published: April 2006

Background

Zenker's diverticulum (ZD) has been increasingly recognized as a site of primary epithelial malignancy. Pitt in 1896 described the first case.

Methods

Between 1990 and 2005, 30 patients affected of esophageal diverticulum were referred to our Department.

Results

The pathological results revealed one case of squamous cell carcinoma. On follow-up 10 years after diverticulectomy alone, the patient was alive and well without evidence of recurrence.

Conclusion

Our case reported provides additional data on clinical decision when the tumor is well localized without full-thickness penetration or extension to the line of resection. In this patient, long-term survival and apparent disease control have been effected by diverticulectomy alone. A case of such long survival is very rare.
Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
Authors: Scott David L , Diez Gerold , Goldmann Wolfgang H
Published: April 2006

Background

Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein.

Results

We have developed a novel computational program that predicts a protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling, Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD spectroscopy and calorimetry experiments confirm that the interfaces predicted for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and vinculin) partially insert into lipid aggregates. The validity of these predictions is supported by an analysis of the available three-dimensional structural data. The lipid interfaces predicted by our algorithm generally contain energetically favorable secondary structures (e.g., an amphipathic alpha-helix flanked by a flexible hinge or loop region), are solvent-exposed in the intact protein, and possess favorable local or global electrostatic properties.

Conclusion

At present, there are few reliable methods to determine the region of a protein that mediates biologically important interactions with lipids or lipid aggregates. Our matrix-based algorithm predicts lipid interaction sites that are consistent with the available biochemical and structural data. To determine whether these sites are indeed correctly identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography.
Cardiovascular system in larval zebrafish responds to developmental hypoxia in a family specific manner
Authors: Moore Francisco B-G , Hosey Michelle , Bagatto Brian
Published: April 2006

Background

Genetic and environmental variation are both known to influence development. Evolution of a developmental response that is optimized to the environment (adaptive plasticity) requires the existence of genetic variation for that developmental response. In complex traits composed of integrated sets of subsidiary traits, the adaptive process may be slowed by the existence of multiple possible integrated responses. This study tests for family (sibship) specific differences in plastic response to hypoxia in an integrated set of cardiovascular traits in zebrafish.

Results

Cardiac output, which is the integrated product of several subsidiary traits, varied highly significantly between families, and families differed significantly in the degree and direction of response to developmental oxygen level. The cardiac output response to oxygen environment was entirely family specific with no significant overall trend due to oxygen level. Constituent physiological variables that contribute to cardiac output all showed significant family specific response to hypoxia. Traits that were not directly related to cardiac output, such as arterial and venous diameter, and red blood cell velocities did not respond to hypoxia in a family specific manner.

Conclusion

Zebrafish families vary in their plastic response to hypoxia. Genetic variation in plastic response to hypoxia may therefore provide the basic ingredient for adaptation to a variable environment. Considerable variation in the degree of familial response to hypoxia exists between different cardiovascular traits that may contribute to cardiac output. It is possible that the integration of several subsidiary traits into cardiac output allows the maintenance of genetic variance in cardiac response.