bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Recovery Patterns for Patients Undergoing Coronary Artery Bypass Grafting and Minimally Invasive Direct Coronary Artery Bypass in the Early Discharge Period
Authors: Zimmerman Lani , Barnason Susan , Brey Beth A. , Catlin Sandy S. , Nieveen Janet
Published: June 2007

The purpose of this pilot study was to compare the postoperative problems, evaluation and response of symptoms, and functional status (physiologic and psychosocial functioning) during the early recovery period (2, 4, and 6 weeks after surgery) in 35 individuals who underwent coronary artery bypass grafting (n=24) or minimally invasive direct coronary artery bypass (n=11). The most frequent postoperative problem reported by the coronary artery bypass grafting group was an incisional infection (either sternal or leg); 26% reported infection at 2 and 4 weeks, and 21% at 6 weeks after surgery. Respiratory problems (pleural effusion, pneumonia) were the second most frequently reported problem, reported by 10% of the subjects at 2 and 4 weeks and by 16% at 6 weeks. Other, less frequent problems were severe nervousness, rhythm problems, and pericarditis. Minimally invasive direct coronary artery bypass patients reported fewer postoperative or cardiac‐related problems, as only 5% indicated a problem with heart failure at both 2 and 4 weeks, and 36% reported being very nervous or having emotional problems at 4 weeks. Unlike postoperative problems, there were numerous similarities in postprocedural symptoms between these two groups. Fatigue, shortness of breath, and pain were the major symptoms reported postdischarge by both groups in this study. In addition, sleeping problems were also fairly prevalent in the coronary artery bypass grafting group, which is understandable, considering the fatigue ratings. Physiologic and psychosocial functioning varied minimally between the two procedures. While there were many similarities in the recovery patterns of both groups, the occurrence of postprocedural problems and symptoms of these two patient groups should be considered by clinicians to further tailor patient education.
The Use of Combination Drug Therapy in the Treatment of Hypertension
Authors: Neutel Joel M.
Published: June 2007

Data from the National Health and Nutritional Examination Survey and from the World Health Organization have clearly demonstrated that, worldwide, less than one quarter of hypertensive patients are adequately controlled by our currently accepted blood pressure (BP) goals. These patients remain at significant risk for the development of cardiovascular disease. Although, there are multiple reasons contributing to inadequate blood pressure control, the most important include: 1) patient compliance; 2) acceptance of inadequate BP control by clinicians; 3) lower BP goals; and 4) the fact that it is very difficult or impossible to achieve adequate BP control with monotherapy in the majority of patients. The use of combination therapy, either as first‐line treatment or much earlier in the course of treating hypertensive patients, may provide the solution to many of these management problems. Low‐dose combination therapy provides several advantages in that: 1) it will be more effective than monotherapy due to the additive effect on BP of complementary drugs; 2) it will provide 24‐hour efficacy with once‐a‐day dosing since most of the low‐dose combination drugs include long‐acting components; 3) it will have a higher response rate than monotherapy and will be effective in most subgroups of hypertensive patients due to the complementary nature of combination therapy; 4) it may have fewer metabolic side effects than higher dose monotherapy since metabolic side effects also tend to be dose dependent; 5) it may have fewer dose‐dependent side effects than monotherapy, as BP control is obtained at lower doses of each of the component drugs; 6) it is more convenient than monotherapy; 7) it may cost less, since low‐dose combination therapy tends to be a little more expensive than each of the components but cheaper than if each of the components were used separately. For these reasons, the use of low‐dose combination therapy as first‐line treatment or much earlier in the stepped‐care approach may play a major role in improving the dismal control rates in hypertensive patients, which may ultimately have a positive impact on the rate of development of cardiovascular disease
Factors Influencing Health‐Related Quality of Life in Cardiac Rehabilitation Patients
Authors: Jamieson Meredith , Wilcox Sara , Webster William , Blackhurst Dawn , Valois Robert F. , Durstine J. Larry
Published: June 2007

Associations of age, gender, cardiac procedure (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty), risk stratification, and number of comorbidities with health‐related quality of life (HRQL) were examined among 217 men and 84 women (mean age, 63±11 years) consecutively enrolled in a phase II cardiac rehabilitation program. Female gender and high‐risk stratification were independently associated with impaired treatment gains in most areas of HRQL. Older age and having a greater number of comorbidities were also associated with impaired gains in specific areas. HRQL was generally lower at baseline but not post‐treatment in coronary artery bypass grafting vs. percutaneous transluminal coronary angioplasty patients. Cardiac rehabilitation patients also had lower HRQL scores than an agematched, normative sample at baseline (most areas) and post‐treatment (mainly on role physical). Findings reinforce the need for cardiac rehabilitation programs to tailor assessments and risk factor modification strategies to patient characteristics associated with low levels of HRQL, especially in women and those with higher risk stratification.
Controlling Hypertension to Reduce the Risk of Stroke
Authors: Lamb Robert E. , Bradford Melissa J.
Published: June 2007

Long‐term hypertension has been implicated as one of the greatest risk factors for the cause of stroke, but yet it is a very controllable one. The risks of stroke increase with age and, as the population of the United States grows older, the number of people who will experience a stroke will greatly increase. In the past, various antihypertensive therapies have proved to lower blood pressure with a resulting decrease in stroke. Stroke can be devastating in terms of quality of life and cost of care; therefore, prevention of stroke should become a priority for all health care professionals. As newer antihypertensive classes of drugs are being studied in high‐risk cardiovascular populations, health care professionals need to educate themselves and their patients regarding new treatment options, where these options belong within treatment guidelines for hypertension, and their relevance in preventing the incidence of stroke. This review briefly summarizes the significance of controlling hypertension to reduce the risk of stroke by reviewing some of the clinical trials that support pharmacologic intervention.
Mouse strain differences in inflammatory responses of colonic mucosa induced by dextran sulfate sodium cause differential susceptibility to PhIP‐induced large bowel carcinogenesis
Authors: Nakanishi Masako , Tazawa Hiroshi , Tsuchiya Naoto , Sugimura Takashi , Tanaka Takuji , Nakagama Hitoshi
Published: June 2007

In mice, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) induces a high incidence of malignant lymphoma and leukemia, but exhibits little, if any, carcinogenic activity in the large intestine after long‐term exposure. However, recent studies have revealed that colonic adenocarcinomas can be efficiently and rapidly induced by combined treatment with PhIP and dextran sulfate sodium (DSS), a potent inducer of colitis. In the present study, the authors investigated the effects of inflammation on PhIP‐induced carcinogenesis using two mouse strains, C57BL/6J and MSM/Ms, showing distinct temporal profiles of inflammatory responses to DSS. A long‐term carcinogenesis experiment conducted with a single i.g. administration of PhIP (200 mg/kg body weight), followed by DSS treatment in drinking water for 4–6 days, revealed an increase in tumor incidence in C57BL/6J mice in accordance with the DSS intake. In contrast, neoplastic lesions were rarely observed in the MSM/Ms strain. From the short‐term exposure to DSS for 4 days, C57BL/6J mice demonstrated severe chronic colitis, accompanied by hyperplastic cryptal epithelium and extensive cellular infiltration. Splenomegaly and swelling of mesenteric lymph nodes were also evident for over 1 month as chronic symptoms of systemic immunological disturbance. However, no inflammatory lesions were detected in MSM/Ms mice. The present results provide strong evidence that prolonged chronic inflammatory responses induced by DSS are directly responsible for the observed enhancement of PhIP‐induced large bowel carcinogenicity. (Cancer Sci 2007; 98: 1157–1163)
Detection of mitochondrial DNA from domestic cattle in bison on Santa Catalina Island
Authors: Vogel A. B. , Tenggardjaja K. , Edmands S. , Halbert N. D. , Derr J. N. , Hedgecock D.
Published: June 2007

In 1924, 14 American bison (Bison bison) were introduced to Santa Catalina Island, California and sporadically supplemented thereafter with additional animals. To reduce the herd and its impact on native vegetation, over 2000 animals have been exported during the past four decades. Today, the herd is estimated to contain around 250 individuals. Genetic analysis was performed on 98 animals removed from the island in 2004. Forty‐four samples (45%) had domestic cattle mitochondrial DNA (mtDNA), 12 (12%) had previously reported bison haplotypes and 42 (43%) had a new haplotype differing by one base pair from a previously reported bison haplotype. A complement of five restriction enzymes was found to be useful in identifying bison with domestic cattle mtDNA.
Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction
Authors: Khor Y. H. , Feltis B. N. , Reid D. W. , Ward C. , Johns D. P. , Wood‐Baker R. , Walters E. H.
Published: June 2007

Background
Back‐titration of inhaled corticosteroid (ICS) dose in well‐controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild‐to‐moderate persistent (inspite of low‐moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high‐dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4–8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration.

Methods
Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphoctyes), bronchoalveolar lavage (BAL) IL‐5 and eotaxin levels and cellular profiles at the end of high‐dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid‐free asthmatics (n=42) and non‐asthmatic controls (n=28).

Results
After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4+/CD8+ T cell ratio, and decreased sICAM‐1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines.

Conclusions
These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back‐titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back‐titration of ICS therapy is monitored.
Three novel CYP21A2 mutations and their protein modelling in patients with classical 21‐hydroxylase deficiency from northeastern Iran
Authors: Baradaran‐Heravi Alireza , Vakili Rahim , Robins Tiina , Carlsson Jonas , Ghaemi Nosrat , A’rabi Azadeh , Abbaszadegan Mohammad Reza
Published: June 2007

Objective  Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive disorders frequently caused by mutations in the steroid 21‐hydroxylase gene (CYP21A2). We describe three novel CYP21A2 mutations in CAH patients.

Design and methods  Sequence analysis of the entire CYP21A2 gene followed by molecular modelling was performed in three unrelated classical CAH patients of northeastern Iranian origin. The active (CYP21A2) and pseudogene (CYP21A1P) alleles were screened for the presence of the new variations in controls.

Results  Two novel missense mutations, F404S in exon 9 and T450P in exon 10, were found in homozygous forms in two female patients with a salt‐wasting (SW) phenotype. These novel variants were screened by allele‐specific polymerase chain reaction (PCR) and excluded in 100 unrelated normal alleles. Prediction of clinical severity, based on molecular modelling and sequence conservation, correlates well with the clinical diagnosis of the patients carrying these mutations. The third novel mutation, a small 10‐bp deletion in exon 1, g.19_28del, was found in a female patient with a simple virilizing phenotype in a compound heterozygous form with the common intron 2 splice mutation (IVS2–13A/C>G). This frameshift mutation causes a premature stop codon at amino acid position 48, L48X, resulting in a nonfunctional protein. The CYP21A1P pseudogene alleles were also screened and none of these novel mutations could be detected.

Conclusions  Three novel mutations were found in the CYP21A2 gene and predicted to drastically impair enzyme activity resulting in severe classic CAH. None of these mutations occurs in the CYP21A1P pseudogene.
Diagnosis and treatment of low‐renin hypertension
Authors: Mulatero Paolo , Verhovez Andrea , Morello Fulvio , Veglio Franco
Published: June 2007

Plasma renin levels can be used to classify hypertension. A significant proportion of hypertensive individuals display a low‐renin profile and thus low‐renin hypertension (LRH) requires appropriate diagnosis and treatment. LRH includes essential, secondary and genetic forms, the most common of which are low‐renin essential hypertension and primary aldosteronism. Several studies have investigated the relationship between PRA status and clinical response to different antihypertensive therapies. The present review will discuss the differential diagnosis of LRH subtypes and the most appropriate treatment options based on the pathophysiological background of this condition.
RET proto‐oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2B
Authors: Zhou Yulin , Zhao Yongju , Cui Bin , Gu Liqun , Zhu Shaoxin , Li Jianjun , Liu Jinbo , Yin Ming , Zhao Tieyun , Yin Zhiqiang , Yu Chaoli , Chen Changyou , Wang Liming , Xiao Buyun , Hong Jie , Zhang Yifei , Tang Zhengyi , Wang Shu , Li Xiaoying , Ning Guang
Published: June 2007

Objective  Multiple endocrine neoplasia type 2 is caused by autosomal dominant gain‐of‐function mutations in the RET proto‐oncogene, which includes multiple endocrine neoplasia type 2A (MEN2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). In this paper we present the phenotype–genotype correlation of 20 unrelated Chinese families with 15 cases of MEN2A and five cases of MEN2B.

Design  Cross‐sectional study.

Patients  A total of 147 members from the 20 families were included. Among them, 119 family members were from MEN2A pedigrees (including 15 MEN2A probands) and 28 members from MEN2B pedigrees (including five MEN2B probands).

Measurements  Genomic DNA was isolated from peripheral blood leucocytes and was amplified using polymerase chain reaction (PCR). DNA analysis for RET mutations in exons 8, 10, 11, 13, 14, 15 and 16 was performed with specific primers.

Results  Thirty‐seven MEN2A and five MEN2B patients were identified as having RET mutations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and hyperparathyroidism (HPT) in the 37 MEN2A patients was 91·9, 56·8 and 10·8%, respectively; the onset of MTC in MEN2A patients was earlier than that of PCC and HPT. Five germline mutations, all located at codon 634 of exon11 in the RET proto‐oncogene, were detected in all of the 37 MEN2A patients. The highest frequency of the five germline mutations was C634Y (46·7%), followed by C634R (26·7%), C634W (13·3%), C634F (6·7%) and C634S (6·7%). No statistical significance was found between the incidence of PCC and different genotypes of codon 634 in MEN2A patients, whereas the incidence of HPT was closely associated with C634R and C634Y. The gene mutation (M918T) at exon16 of the RET proto‐oncogene was present in five MEN2B probands.

Conclusions  RET proto‐oncogene mutations were restricted to codon 634 and 918 in Chinese families with MEN2A and MEN2B. In general the genetic characteristics of these patients with MEN2A and MEN2B reflect the general pattern around the world and it remains to be determined with larger studies in China whether Chinese patients have a different genetic pattern of mutations.
Altered expression of adhesion molecules in inflammatory cervical smears
Authors: Politi E. N. , Lazaris A. C. , Kehriotis M. , Papathomas T. G. , Nikolakopoulou E. , Koutselini H.
Published: June 2007

Objective:  The aim of the present study was to evaluate the expression of pan‐cadherin and β‐catenin in cervical smears with various types of infectious agents.

Patients and Methods:  Cervical smears obtained from 53 women, aged 21–65 years, with a diagnosis of specific inflammation were examined in our study. Eighteen subjects were infected by Candida albicans, 18 by Gardnerella vaginalis, nine by Bacteroides spp. and eight by Chlamydia trachomatis. All infectious agents found in the smears were at the same time confirmed by the microbiological laboratory methods. We performed a biotin–streptavidin‐peroxidase immunocytochemical method using anti‐β‐catenin (Clone 12F7) and anti‐pan‐cadherin (pan, polyclonal) antibodies.

Results:  Aberrant expression of pan‐cadherin was found in the cytoplasmic membrane of glandular, metaplastic, superficial and intermediate squamous cells in all types of infections. With regard to β‐catenin, this was expressed in majority (90%) of glandular and metaplastic cells in all types of infections and in a small proportion (15%) of superficial and intermediate squamous cells in infections caused by C. albicans and G. vaginalis.

Conclusion:  Our data show that infectious agents may cause alterations in the expression and distribution of these adhesive molecules, which can be recognized in cervical smears. Additional studies in larger sets of patients should help clarify this issue further.
Altered endothelial gene expression associated with hereditary haemorrhagic telangiectasia
Authors: Thomas B. , Eyries M. , Montagne K. , Martin S. , Agrapart M. , Simerman‐François R. , Letarte M. , Soubrier F.
Published: June 2007

Background  Mutations in endoglin (ENG) and activin receptor‐like kinase 1 (ALK‐1 or ACVRL1) genes are the underlying basis of hereditary haemorrhagic telangiectasia (HHT) types 1 and 2, respectively. Both genes belong to the transforming growth factor‐β (TGF‐β) receptors superfamily and are expressed in endothelial cells. The current model for HHT is that ENG or ALK‐1 haplo‐insufficiency affects angiogenesis and predisposes to vascular dysplasia and arteriovenous malformations.

Materials and methods  Using microarray technology, we compared human umbilical vein endothelial cells (HUVEC) from newborns with ENG or ALK‐1 mutations to control cells to search for gene profiles associated with early stages of the disease. Real‐time polymerase chain reaction and Western blot analysis were used to validate a subset of the modulated genes and functionally related genes.

Results  Our results indicate that HHT endothelial cells in vitro display several gene expression disturbances, including genes associated with the activation phase of angiogenesis, with cell guidance and intercellular connections, and also with the TGF‐β pathway. Hierarchical clustering using modulated genes enables discrimination between affected and non‐affected samples.

Conclusion  HHT HUVECs display gene modulations which can suggest that ENG and ALK‐1 haplo‐insufficiency induces compensatory regulatory mechanisms at the expression levels.
Effects of infectious disease on plasma lipids and their diagnostic significance in critical illness
Authors: Lüthold S. , Berneis K. , Bady P. , Müller B.
Published: June 2007

Background  Plasma lipids can be affected by acute illnesses. The present study attempts to characterize the impact of infectious disease on plasma lipids in critical illness. It also aims to determine the value of plasma lipid routine measurements in the diagnosis of infection in critical illness in comparison to markers of infection and acute phase reactants.

Materials and methods  An observational study was carried out in 101 critically ill patients admitted consecutively to a medical intensive care unit in a university medical centre. Levels of total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TG), and additional variables were measured in blood samples taken on the day of admission.

Results  In critically ill patients significantly lower levels of HDL‐C and TC were found in infectious disease patients compared to non‐infectious disease patients (P < 0·001). No significant differences in levels of TG were found between infectious and non‐infectious disease patients. Using receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) value for HDL‐C and TC in the diagnosis of infection was 0·791 (P < 0·001) and 0·730 (P < 0·001), respectively. At a cutoff value for HDL‐C of ≤ 0·78 mmol L−1, a sensitivity of 71·7% and a specificity of 86·0% were recorded. The AUC value of HDL‐C was significantly (P < 0·001) inferior to procalcitonin (AUC: 0·967, P < 0·001) and non‐significantly inferior to C‐reactive protein (CRP) (AUC: 0·874, P < 0·001). HDL‐C correlated with albumin (r = 0·7, P < 0·001) and CRP (r = –0·54, P < 0·001), but not with the Acute Physiology and Chronic Health Evaluation II score. There was no significant difference between the plasma lipid concentrations in survivors and non‐survivors.

Conclusion  In critically ill infected patients, HDL‐C and TC levels are lower than in non‐infected critically ill patients. In this study the diagnostic accuracy of CRP is not better than the one of HDL‐C. The diagnostic accuracy of procalcitonin is superior to HDL‐C.
Mutations of chronic granulomatous disease in Turkish families
Authors: Köker M. Y. , Sanal Ö. , De Boer M. , Tezcan İ. , Metin A. , Ersoy F. , Roos D.
Published: June 2007

Background  Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by impairment of intracellular microbicidal activity of phagocytes. Mutations in one of four known NADPH‐oxidase components preclude generation of superoxide and related antimicrobial oxidants, leading to the phenotype of CGD. Defects in gp91‐phox, encoded by CYBB, lead to X‐linked CGD and have been reported to be responsible for approximately 70% of all CGD cases. The aim of this study was to identify the CGD mutations in a group of Turkish CGD patients and to evaluate the predominance of CGD mutations as X‐linked or autosomal recessive (AR) within the Turkish CGD families with known mutations.

Materials and methods  Two Turkish CGD families were included in the study, and mutations were identified by sequence analysis of DNA and RNA from peripheral blood in the patients. Before mutation analysis, subgroup analysis of patients was made by flow cytometry with antibodies against NADPH oxidase components and with DHR‐123 oxidase activity assay. For comparison, we included previously reported results from four other Turkish CGD families.

Results  Two different mutations were identified, one of them a novel mutation g.700G>T located in exon 7 of CYBB, and the other a hot‐spot mutation located in exon 2 of the NCF1 gene. These mutations were detected in three patients from two Turkish families.

Conclusions  Until now, we have altogether identified mutations in six Turkish CGD families. In this limited number of families our results show AR‐CGD in two‐thirds of the Turkish families investigated, in contrast to previous reports in the literature. This is probably due to the high rate of consanguineous marriages in Turkey. Consanguineous parents were found in 75% of the families with AR‐CGD patients, which favours homozygous deficiencies.
Denitrification characteristics of subtropical soils in China affected by soil parent material and land use
Authors: Xu Y. B. , Cai Z. C.
Published: June 2007

Forty‐five soil samples were collected from rice paddy land (R), tea garden land (T), forestland (F), brush land (B), and upland (U) in Jiangxi province, a subtropical region of China. These soils were derived from Quaternary red earth (Q), Tertiary red sandstone (S), and granite (G). Their denitrification capacities were determined after treatment with 200 mg NO3−‐N kg−1 soil by measuring changes in NO3−‐N content during a 28‐day anaerobic incubation under N2 gas in the headspace, at 30°C. The subtropical soils studied here were characterized by generally small denitrification capacities, ranging from no denitrification capacity to complete disappearance of added NO3−‐N within 11 days of incubation. With few exceptions, NO3−‐N reduction with incubation time followed a first‐order relationship with reaction constants of 0 – 0.271 day−1, but the data could be simulated better by a logarithmic relationship. Thus, denitrification capacity was determined by the reaction constant of the first‐order reaction, the slope of the logarithmic relationship, and the averaged NO3−‐N reduction rate in the first 7 days of anaerobic incubation (ranging from 0 to 28.5 mg kg−1day−1), and was significantly larger in the soils derived from G than from Q and S for all land uses except for rice paddy land. Soil organic carbon and nitrogen availability are the key factors that determine differences in denitrification capacity among the three soil parent materials. Rice cultivation significantly promoted denitrification capacity compared with the other four land uses and masked the effect of soil parent materials on denitrification capacity. This is most likely due to increases in organic carbon and total N content in the soil, which promoted the population and biological activities of microorganisms which are able to respire anaerobically when the rice soil is flooded. Neither the increased pH of upland soil caused by the addition of lime for upland crop production, nor the decreased pH of the tea garden soil by the acidification effect of tea plants altered soil denitrification capacity. Our results suggest that land use and management practices favour soil carbon and/or nitrogen accumulation and anaerobic microorganism activities enhance soil denitrification capacity.
Comparison of chemical fractionation methods for isolating stable soil organic carbon pools
Authors: Helfrich M. , Flessa H. , Mikutta R. , Dreves A. , Ludwig B.
Published: June 2007

Stable soil organic matter (SOM) is important for long‐term sequestration of soil organic carbon (SOC), but the usefulness of different fractionation methods to isolate stable SOM is open to question. We assessed the suitability of five chemical fractionation methods (stepwise hydrolysis, treatment with H2O2, Na2S2O8, NaOCl, and demineralization of the NaOCl‐resistant fraction (NaOCl + HF)) to isolate stable SOM from soil samples of a loamy sand and a silty loam under different land use regimes (grassland, forest and arable crops). The apparent C turnover time and mean age of SOC before and after fractionation was determined by 13C and 14C analysis. Particulate organic matter was removed by density fractionation before soils were exposed to chemical fractionation. All chemical treatments induced large SOC losses of 62–95% of the mineral‐associated SOC fraction. The amounts of H2O2‐ and Na2S2O8‐resistant SOC were independent from land use, while those of NaOCl‐ (NaOCl + HF)‐ and hydrolysis‐resistant SOC were not. All chemical treatments caused a preferential removal of young, maize‐derived SOC, with Na2S2O8 and H2O2 being most efficient. The mean 14C age of SOC was 1000–10000 years greater after chemical fractionation than that of the initial, mineral‐associated SOC and mean 14C ages increased in the order: NaOCl < NaOCl + HF ≤ stepwise hydrolysis ≪ H2O2≈ Na2S2O8. None of the methods appeared generally suitable for the determination of the inert organic matter pool of the Rothamsted Carbon Model. Nonetheless, our results indicate that all methods are able to isolate an older, more stable SOC fraction, but treatments with H2O2 and Na2S2O8 were the most efficient ones in isolating stable SOM.
Multidecadal to millennial‐scale shifts in drought conditions on the Canadian prairies over the past six millennia: implications for future drought assessment
Authors: MICHELS ASTRID , LAIRD KATHLEEN R. , WILSON SUSAN E. , THOMSON DAVID , LEAVITT PETER R. , OGLESBY ROBERT J. , CUMMING BRIAN F.
Published: June 2007

Three high‐resolution climatic reconstructions, based on diatom analyses from lake sediment cores from the Canadian prairies, show that shifts in drought conditions have prevailed on centennial to millennial time scales for at least the past six millennia. These shifts in mean aridity exhibit broad regional synchrony, with particularly pronounced shifts at all sites between ∼1700–2000 cal. yr bp and ∼3600–3900 cal. yr bp, as well as at ∼5400–5500 cal. yr bp for the two sites which extend back to at least 6000 cal. yr bp. The two Saskatchewan lakes exhibited significant coherence in both the timing and direction of these shifts, whereas inferred changes at the westernmost site in Alberta were significantly correlated to the Saskatchewan sites, but opposite in sign, and exhibited more high‐frequency variation on the scale of centuries. The mechanisms behind these abrupt shifts in aridity are poorly understood, but may be linked to changes in oceanic–atmospheric interactions that influence the mean position of the jetstream and the associated storm tracks. Natural shifts in mean climatic conditions may accelerate with increasing carbon dioxide levels intensifying the likelihood of extreme droughts in North American prairies.
Development of a stable isotope index to assess decadal‐scale vegetation change and application to woodlands of the Burdekin catchment, Australia
Authors: KRULL EVELYN , BRAY STEVEN , HARMS BEN , BAXTER NATHALIE , BOL ROLAND , FARQUHAR GRAHAM
Published: June 2007

Forty‐four study sites were established in remnant woodland in the Burdekin River catchment in tropical north‐east Queensland, Australia, to assess recent (decadal) vegetation change. The aim of this study was further to evaluate whether wide‐scale vegetation ‘thickening’ (proliferation of woody plants in formerly more open woodlands) had occurred during the last century, coinciding with significant changes in land management. Soil samples from several depth intervals were size separated into different soil organic carbon (SOC) fractions, which differed from one another by chemical composition and turnover times. Tropical (C4) grasses dominate in the Burdekin catchment, and thus δ13C analyses of SOC fractions with different turnover times can be used to assess whether the relative proportion of trees (C3) and grasses (C4) had changed over time. However, a method was required to permit standardized assessment of the δ13C data for the individual sites within the 13 Mha catchment, which varied in soil and vegetation characteristics. Thus, an index was developed using data from three detailed study sites and global literature to standardize individual isotopic data from different soil depths and SOC fractions to reflect only the changed proportion of trees (C3) to grasses (C4) over decadal timescales. When applied to the 44 individual sites distributed throughout the Burdekin catchment, 64% of the sites were shown to have experienced decadal vegetation thickening, while 29% had remained stable and the remaining 7% had thinned. Thus, the development of this index enabled regional scale assessment and comparison of decadal vegetation patterns without having to rely on prior knowledge of vegetation changes or aerial photography.
Oxidative stress biomarkers and hormonal profile in human patients undergoing varicocelectomy
Authors: Hurtado de Catalfo Graciela E. , Ranieri‐Casilla Adalberto , Marra Fernando A. , De Alaniz María J. T. , Marra Carlos A.
Published: June 2007

The aetiology of varicocele is multifactorial although hormonal imbalance and oxidative stress play a key role in the progression of illness. No conclusive evidence has been presented previously, describing the changes in these two factors and the evolution of patients after varicocelectomy. Semen characteristics and hormonal profile were analysed in 36 infertile men with unilateral left varicocele and 33 age‐paired controls (proved to be fertile men), after careful inclusion/exclusion selection criteria. Liposoluble and hydrosoluble antioxidants, oligoelements and enzyme activities of the antioxidant defence system were also determined in plasma and erythrocyte from antecubital and spermatic veins, and in spermatozoa. Data were compared between groups at different times before and after varicocelectomy. Decreased levels of liposoluble and hydrosoluble antioxidants and increased activities of the antioxidant defence system enzymes were observed in patients compared with controls. Varicocelectomy normalized this condition at different post‐surgical times. Levels of Zn and Se in seminal plasma, protein carbonyls and fragmented DNA remained elevated up to 1 month after surgery. Luteinizing and follicle stimulating hormone concentrations exhibited a biphasic behaviour while testosterone was diminished in patients but normalized soon after varicocelectomy. The results clearly demonstrate the link between the antioxidant defence system, hormonal status and semen characteristics along the post‐varicocelectomy period. We suggest that oxidative biomarkers may be appropriate in controlling the evolution of post‐varicocelectomy patients, and antioxidant supplementation may improve the clinical condition of infertile men with varicocele.
Fertility treatment in male cancer survivors
Authors: Schmidt Kirsten Louise Tryde , Carlsen Elisabeth , Andersen Anders Nyboe
Published: June 2007

The present study reviews the use of assisted reproductive technology in male cancer survivors and their partners. As antineoplastic treatment with chemotherapy or radiation therapy, has the potential of inducing impairment of spermatogenesis through damage of the germinal epithelium, many male cancer survivors experience difficulties in impregnating their partners after treatment. The impairment can be temporary or permanent. While many cancer survivors regain spermatogenesis months to years after treatment, some become infertile with a‐, oligo‐ or azoospermia. An option to secure the fertility potential of young cancer patients is to cryopreserve semen before cancer treatment for later use. A desired pregnancy may be obtained in couples where the husband has a history of cancer, using assisted reproductive technology with either fresh or cryopreserved/thawed semen. Successful outcomes have been obtained with intrauterine insemination (IUI) as well as in vitro fertilization (IVF) with or without the use of intracytoplasmic sperm injection (ICSI). In conclusion, male cancer survivors and their partners who have failed to obtain a pregnancy naturally within a reasonable time frame after end of treatment should be referred to a fertility clinic.
Characterization of human sperm N‐acetylglucosaminidase
Authors: Perez Martinez S. L. , Menendez Helman R. J. , Zitta K. S. , Brandelli A. , Miranda P. V.
Published: June 2007

N‐acetylglucosaminidase (NAG) is particularly active in mammalian spermatozoa and appears to be involved in fertilization. Although it is assumed that this enzyme is acrosomal, previous results from our laboratory suggest the presence of NAG at the sperm plasma membrane level. The present study attempted to analyse the subcellular distribution of this enzyme in human spermatozoa. Sperm were incubated under different conditions and NAG activity measured in the soluble extracts and cell pellets using a specific fluorometric substrate. A significant proportion of NAG activity was released when sperm were incubated in culture medium, suggesting a weak association with the plasma membrane. This location was confirmed by western blot analysis of plasma membrane fractions and immunofluorescence on non‐permeabilized sperm, which showed a positive signal mainly on the acrosomal domain. The distribution of NAG activity between plasma membrane and acrosome was analysed after cell disruption by freezing and thawing. Triton X‐100 stimulated sperm and epididymal NAG activity but not the enzyme obtained from other sources. In addition, biotinylated human recombinant NAG was able to bind to human sperm. Finally, after sperm incubation under capacitating conditions, NAG total activity increased and the sperm enzyme lost its ability to be stimulated by Triton X‐100. The possible connection of these results with sperm maturation, capacitation and NAG participation in primary binding to the zona pellucida, was discussed.
Drosophila spermatogenesis: insights into testicular cancer
Authors: Hime G. R. , Loveland K. L. , Abud H. E.
Published: June 2007

Geneticists have a long history of studying reproduction in the fruitfly, Drosophila melanogaster, and in recent years it has become apparent that many of the genes that regulate invertebrate reproduction have been conserved through vertebrate evolution. As with other higher eukaryotes, spermatogenesis in Drosophila is characterized by a regenerative germline stem cell population that divides asymmetrically to produce mitotic spermatogonia which will eventually differentiate into spermatocytes. Germline tumours consisting of undifferentiated germ cells have been associated with both loss‐of‐function mutations and ectopic gene expression. While the genesis of these tumours may not be identical to human germ cell tumours many of the genes that regulate stem cell proliferation and aberrant over‐proliferation in the Drosophila testis provide candidate molecules that may underlie the genetic programmes that contribute to human testicular oncogenesis.
Relationship between sperm apoptosis signalling and oocyte penetration capacity
Authors: Grunewald S. , Said T. M. , Paasch U. , Glander H.‐J. , Agarwal A.
Published: June 2007

Human sperm have been documented to display apoptosis‐like features such as externalization of phosphatidylserine (EPS), disruption of the transmembrane mitochondrial potential (MMP) and activation of caspases. Our aim was to evaluate possible association between activation of the apoptosis cascade in human sperm and its oocyte penetration capacity using the zona free hamster oocyte penetration assay (SPA). Semen specimens from 76 unselected donors were subjected to double density gradient centrifugation followed by incubation under capacitating conditions for 3 h and SPA. Apoptosis signalling was monitored by assessment of EPS, disruption of MMP and activation of caspase‐3 by flow cytometry. Semen samples with subnormal SPA values (<20% penetrated oocytes) contained significantly higher amounts of spermatozoa with EPS, disrupted MMP and activated caspase‐3 compared with those samples with normal SPA values (>20% penetrated oocytes, p < 0.01). All three apoptosis markers showed a significantly negative correlation with the percentage of penetrated oocytes (p < 0.01). Apoptosis‐related signalling appears to have a negative association with sperm–oocyte penetration. The exclusion of sperm presenting with those apoptosis‐related features during assisted reproduction may improve success rates of procedures such as intrauterine insemination and in vitro fertilization.
KIT and RAS signalling pathways in testicular germ cell tumours: new data and a review of the literature
Authors: Goddard N. C. , McIntyre A. , Summersgill B. , Gilbert D. , Kitazawa S. , Shipley J.
Published: June 2007

Testicular germ cell tumours (TGCTs) are the leading cause of cancer deaths in young male Caucasians. Identifying changes in DNA copy number can pinpoint genes involved in tumour development. We defined the smallest overlapping regions of imbalance in TGCTs using array comparative genomic hybridization analysis. Novel regions, or regions which refined those previously reported, were identified. The expression profile of genes from 12p, which is invariably gained in TGCTs, and amplicons defined at 12p11.2‐12.1 and 4q12, suggest KRAS and KIT involvement in TGCT and seminoma development, respectively. Amplification of these genes was not found in intratubular germ cell neoplasia adjacent to invasive disease showing these changes, suggesting their involvement in tumour progression. Activating mutations of RAS genes (KRAS or NRAS) and overexpression of KRAS were mutually exclusive events. These, correlations between the expression levels of KIT, KRAS and GRB7 (which encodes an adapter molecule known to interact with the KIT tyrosine kinase receptor) and other reported evidence reviewed here, are consistent with a role for activation of KIT and RAS signalling in TGCT development. In order to assess a role for KIT in seminomas, we modulated the level of KIT expression in TCam‐2, a seminoma cell line. The likely seminomatous origin of this cell line was supported by demonstrating KIT and OCT3/4 overexpression and gain of 12p material. Reducing the expression of KIT in TCam‐2 through RNA inhibition resulted in decreased cell viability. Further understanding of KIT and RAS signalling in TGCTs may lead to novel therapeutic approaches for these tumours.
In vivo administration of doxazosin in rats highly decreases serum circulating levels of testosterone through a mechanism involving the testicular renin–angiotensin system
Authors: De La Chica‐Rodríguez S. , Cortés‐Denia P. , Ramírez‐Expósito M. J. , Arias de Saavedra J. M. , Sánchez‐Agesta R. , Del Cármen Pérez M. , Martínez‐Martos J. M.
Published: June 2007

Men are at greater risk of cardiovascular and renal diseases than women. Several hypertensive rat models also exhibit gender differences in blood pressure. Although the mechanisms responsible for these gender differences are not clear, androgens have been shown to promote hypertension. Testosterone is produced by Leydig cells under the regulation of catecholamines acting through both α‐ and β‐adrenoceptors. Some investigators have postulated a putative role of angiotensin II (AngII) in modulating the action of gonadotropin in Leydig cells, inhibiting testosterone production. In the present work, we analysed the potential mechanism by which the testicular renin–angiotensin system (RAS) decreases the serum circulating levels of testosterone after the in vivo administration of the long‐acting selective α1‐adrenergic receptor antagonist doxazosin. RAS was analysed through assessment of the activity of its proteolytic regulatory enzymes. We can conclude that the testicular testosterone production, at least in rat, is regulated by catecholamines through a mechanism involving α1‐adrenergic receptors and RAS, with a putative role for AngIII. Because doxazosin is usually used as a pharmacological therapy in the treatment of hypertension and benign prostatic hyperplasia, our results could also indicate that its benefits are due, at least in part, to decreased serum circulating levels of testosterone.
DNA damage response in human testes and testicular germ cell tumours: biology and implications for therapy
Authors: Bartkova J. , Rajpert‐De Meyts E. , Skakkebæk N. E. , Lukas J. , Bartek J.
Published: June 2007

DNA damage response (DDR) is emerging as a physiological anti‐cancer barrier in early stages of cancer development, as shown for several types of solid cancers derived from somatic cells. Here we discuss our recently published and unpublished results on the exceptional paucity of such constitutive activation of the DDR machinery in human testicular germ cell tumours (TGCTs), including their common pre‐invasive stage of carcinoma in situ (CIS). Our conclusions are supported by immunohistochemical analyses of multiple markers of activated DNA damage signalling, such as the phosphorylated ATM and Chk2 checkpoint kinases and phosphorylated histone H2AX. We propose that the unique lack of DDR activation in TGCTs reflects the biology of their cell of origin, the gonocyte. Furthermore, we propose that the lack of DDR activation avoids the pressure to select for mutations in DDR genes such as p53 or ATM, and the resulting intact DDR machinery may have implications for the exceptional curability of TGCTs by DNA damaging therapies.
Non‐tumoural parenchyma in Leydig cell tumours: pathogenetic considerations
Authors: Cajaiba M. M. , Reyes‐Múgica M. , Rios J. C. S. , Nistal M.
Published: June 2007

Little is known about the pathogenesis of Leydig cell tumours (LCTs) of the testis. The observation of several associated dysgenetic features in the non‐tumoural parenchyma and in the contralateral testes of men with testicular germ cell neoplasms has served as the basis to propose that there may be a common mechanism for different male reproductive disorders. However, the possible relationship between LCTs and other testicular lesions has not been explored. Here we describe the presence of primary lesions in the non‐tumoural parenchyma of testes with LCT, from which we try to establish possible pathogenetic associations. We studied the non‐tumoural parenchyma adjacent to 16 LCT specimens. Parameters as Leydig cell hyperplasia (LCHY), qualitative evaluation of the germinal epithelium and spermatogenesis, the presence of Sertoli cell‐only tubules (SCOT), and the Sertoli cell nuclear morphology were consistently assessed in all cases. SCOT associated with Sertoli cell dysgenetic morphology was the most frequent finding, present in 50% of the cases. Another interesting finding was the presence of LCHY in four cases (25%). Abnormal spermatogenesis was found in 81.25% of the cases, and it consisted of lesions of the adluminal or basal compartments of seminiferous tubules. The occurrence of either dysgenetic Sertoli cells or LCHY adjacent to LCTs could represent primary anomalies, resulting from a common insult also involved in tumourigenesis. The abnormalities in spermatogenesis observed here are likely to represent consequences of either tumour compression or abnormal hormonal production. The significance of these associations merits further investigation regarding a common pathogenesis.
Genomic and expression profiling of human spermatocytic seminomas: pathogenetic implications
Authors: Looijenga Leendert H.J. , Stoop Hans , Hersmus Remko , Gillis Ad J. M. , Wolter Oosterhuis J.
Published: June 2007

Traditionally, germ cell tumours (GCTs) have been classified based on their histological appearance, i.e. the differentiation of lineages. Various subtypes of seminomas have been identified in a number of classification systems, including anaplastic and spermatocytic seminoma. Here we present conclusive evidence that spermatocytic seminomas are GCTs with a separate pathogenesis from seminoma, and should therefore not be considered as a variant of seminoma. Moreover, the different putative animal models, either spontaneous or induced, are discussed in the context of their value as model for human GCTs. The canine seminomas are currently considered as the most informative model for human spermatocytic seminomas.