bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating qualitative methods into occupational health research: a study of women flight attendants: Table 1
Authors: Ballard T J , Corradi L , Lauria L , Mazzanti C , Scaravelli G , Sgorbissa F , Romito P , Verdecchia A
Published: January 2004

Aims:To identify possible work related sources of psychosocial stress in order to develop pertinent questionnaire items for a cross-sectional health survey of 3000 Italian women flight attendants, and to solicit suggestions on improving survey participation.

Methods:Qualitative study in which 26 current and former women flight attendants participated: three focus groups of 6–7 participants each and six in-depth individual interviews. The session themes included positive and negative aspects of the job; relationships with colleagues, superiors, and passengers; perception of occupational risk for serious diseases; compatibility of work and family; and experiences of work related sources of stress and their effect on health. A transcript based analysis of the focus groups and interviews was used to identify emerging themes related to risk factors for mental health problems.

Results:The participants indicated that mental health was a major concern. Several work related risk factors possibly related to adverse outcomes, such as depression and anxiety, were highlighted. These included isolation and solitude, fears of being inadequate partners and mothers due to job demands, passenger relationships, and lack of protection by employers with respect to workplace exposures and violent passengers. The information gained was used to develop a mental health module for inclusion in the health survey questionnaire which included questions on history of severe depression or anxiety, suicidal ideation or attempt, substance abuse, workplace sexual harassment, social support, leisure time activities, relationship with a partner, and role as mother.

Conclusions:Employing qualitative methods to identify work related sources of psychosocial stress enabled development of pertinent questionnaire items for a cross-sectional epidemiological study of women flight attendants. Follow up qualitative research may be necessary in order to put the cross-sectional study findings into context and to explore actions or strategies for preventing work related health problems evidenced from the survey.
Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men
Authors: Perez-Gomez B , Pollán M , Gustavsson P , Plato N , Aragonés N , López-Abente G
Published: January 2004

Aims:To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers.

Methods:Male workers employed in 1970 and living in the country in 1960 were followed up from 1971 to 1989 using the Swedish Registers of Death and Cancer. A more specifically exposed subcohort included men reporting the same occupation in 1960 and 1970. For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. To diminish the influence of socioeconomic factors, intrasector analyses, comparing only jobs belonging to the same occupational sector, were performed. Risk patterns for different locations were compared.

Results:High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those found in thorax, the most frequent location. Correlation between head/neck and thorax was moderate. Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and for aircraft pilots/navigators/flight engineers in lower limbs.

Conclusions:High RRs in the trunk among occupations with UV exposure from artificial sources suggest an effect not restricted to exposed sites. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers suggests local effects of exposures. The not previously reported risk excess in this job and in fur related processes, and the RR in electrical fitters and telephone/telegraph installers deserve further investigation. Disparities between locations, as RRs in thorax and limbs, may reflect differences in aetiological mechanisms.
The inhibition of mercury absorption by dietary ethanol in humans: cross-sectional and case-control studies
Authors: Martin M D , Naleway C
Published: January 2004

Background:Since the inhibition of mercury absorption by ethanol was serendipitously discovered in 1965,1a limited number of small number studies with both animal and human subjects have reported results consistent with this finding.

Aims:To investigate this phenomenon in a large scale human study with low level Hg exposed dentists.

Methods:Data were collected for a sample of 1171dentists, and both cross sectional and case-control methods were utilised to examine the data.

Results:Abstainers (n = 345) had significantly higher urinary mercury concentrations (HgU) than drinkers (n = 826): 5.4 μg/lv4.8 μg/l. Multiple linear regression showed a significant effect of ethanol dose on HgU after adjusting for potential confounders. A case-control analysis in which cases were defined as those individuals with urinary Hg concentrations of ⩾15 μg/l (≈ top 5%), and controls as those with concentrations of <1.0 μg/l (≈ bottom 5%), showed a clear protective dose-response relation; there was a decreasing risk of being a “case” (having an HgU ⩾15 μg/l) with increasing ethanol consumption. The significance of the adjusted model is p<0.001, and the χ2test for trend across ethanol consumption categories in the adjusted model is p<0.05, confirming the dose-response relation.

Conclusion:We believe that this straightforward investigation provides the first specific confirmation in a large scale human study of the inhibitory effect of ethanol on urinary mercury concentration, and by inference, on mercury absorption.
Ag ADSORPTION ON THE W(100) PLANE
Authors: CHOI D. S. , KIM D. H. , KIM S. S.
Published: January 2004

The surface structure of Ag/W(100) has been studied using LEED and Low Energy Ion Scattering Spectroscopy (ISS). We find that Ag coverages are saturated at 0.5 ML after annealing at 800°C regardless of the initial coverages between 0.7~1.0 ML. We observe a c(2×2) image after annealing the Ag/W(100) sample at 800°C. Using the ISS technique the adsorption site of Ag on the c(2×2) surface is found to be the center of the nearest two atoms on the W(100) surface. The height of the Ag adsorption layer is 1.58 Å above the W(100) surface.
DETONATION OF MOLECULAR PRECURSORS AS A TOOL FOR THE ASSEMBLY OF NANO-SIZED MATERIALS
Authors: ZHU ZHENPING
Published: January 2004

The detonation of carbon- or nitrogen-containing explosives not only produces powerful shock waves but also provides elemental building blocks and a unique high-pressure and high-temperature physical environment for the construction of various nanostructures. This review highlights the situation and key progresses in the detonation approach towards diamond nanoparticles, graphitic carbon nanotubes, fullerene molecules, and gallium nitride nanocrystals. Further extension of the peaceful-use detonation applications and rational reactor design are also proposed.
PERPENDICULAR-TO-PLANE MAGNETORESISTANCE IN La0.7Ca0.3MnO3/LaNiO3 SUPERLATTICES: THE EFFECTS OF INTERFACIAL DISORDER AND SPIN DIFFUSION ON CHARGE TRANSPORT
Authors: PADHAN PRAHALLAD , BUDHANI R. C.
Published: January 2004

Current perpendicular-to-plane (CPP) magnetoresistance (MR) of La 0.7 Ca 0.3 MnO 3/ LaNiO 3 superlattices sandwiched between two YBa 2 Cu 3 O 7 thin film electrodes is reported. The CPP-MR in the temperature window of 20 K to 80 K is larger by a factor of 7~15 compared to current-in-plane (CIP) MR. Both CPP and CIP-magnetoresistance decrease with temperature below ~ 20 K. The MR at T<40 K is also strongly hysteretic and does not saturate even at 4 Tesla. Measurements of saturation moment and modeling of the perpendicular-to-plane resistance suggest disorder at the ferromagnetic non-magnetic layer interfaces which dominate the MR. The relative orientation of magnetization in the ferromagnetic layers seems to play only a subservient role in the creation of magnetoresistance.
Reproductive Biology of the Slender Loris (Loris lydekkerianus lydekkerianus)
Authors: Radhakrishna Sindhu , Singh Mewa
Published: January 2004

The slender loris (Loris lydekkerianus lydekkerianus), a nocturnal prosim-ian, was studied for 21 months in its natural habitat of scrub jungle in Dindigul, south India. Here we report on its reproductive biology. Identified and unidentified lorises were observed for a total of 2,656 h. Reproductive seasonality was seen, with births and oestrus observed to be highest in April–June and October–December. The mating system was promiscuous with 1 female mating successively with 3–4 males. A gestation period of 5.5 months and an inter-birth interval of 7 months were recorded. Adult females had a reproductive potential of 4 infants per year. The findings presented in this paper constitute the first information on the life history parameters of wild slender lorises.
Increased Urinary Concentration of Collagen Type II C-Telopeptide Fragments in Patients with Osteoarthritis
Authors: Jung M. , Christgau S. , Lukoschek M. , Henriksen D. , Richter W.
Published: January 2004

Objective: Osteoarthritis (OA) is characterized by a progressive degeneration of articular cartilage and loss of joint function. We hypothesized that degradation of articular cartilage results in increased fragmentation of collagen type II. Thus, the concentrations of degradation products of this major cartilage matrix protein may increase in body fluids of patients with OA. Methods: Monoclonal antibodies specific for a human collagen type II C-telopeptide (CTx-II) fragment were used in an ELISA for quantification of collagen type II fragments in urine. Clinical assessment of 88 patients with advanced OA of either hip or knee and 48 age-matched controls was performed with the Harris hip score, the Merle d’Aubigné score and a knee score. Joint space narrowing and the Kellgren and Lawrence score were assessed as radiological signs of OA. Results: The concentration of CTx-II was significantly higher in OA patients compared with controls (527 vs. 190 ng/mmol, p < 0.001) whether the patients were diagnosed with hip OA (n = 51) or knee OA (n = 37). Mean CTx-II levels were higher in hip OA than in knee OA and a slight increase in levels with age was observed in the controls, but not in OA subjects. Conclusion: Elevation of CTx-II in urine of patients with severe OA compared with a control group suggests that collagen type II derived fragments may serve as markers for OA.
Engraftment of Adult Human Lung Tissue in Nonobese Diabetic/Severe Combined Immunodeficient Mice: A Novel Lung Epithelial Regeneration Model
Authors: Yonou Hiroyuki , Yokose Tomoyuki , Yoshikawa Takeshi , Kanomata Naoki , Kamijo Tomoyuki , Hasebe Takahiro , Nagai Kanji , Ito Hiroshi , Yamasaki Akira , Hatano Tadashi , Ogawa Yoshihide , Emura Makito , Ochiai Atsushi
Published: January 2004

Objectives: Injury causes the disruption of homeostatic cell-cell interactions and epithelial regeneration is part of the threshold response. Due to the lack of a good animal model for the investigation of these mechanisms, the kinetics of cell proliferation after injury to the human respiratory tract are poorly understood. Methods: To create a better model of human bronchioloalveolar epithelial regeneration, we engrafted adult human lung tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Then the lung tissue was studied at various times up to 20 weeks after implantation. Results: The xenografts of bronchiolar epithelium showed characteristic features, including positivity for specific human antigens, and extensive regeneration was observed within 8 weeks after implantation. In addition, a few alveolar type II epithelial cells expressing prosurfactant protein C were detected in some areas. The distal alveolar spaces were filled with protein-rich material and were markedly dilated. Abundantly ciliated secretory epithelium, which was similar to normal adult bronchiolar epithelium, was observed within 16 weeks after implantation in the mice. All of the human lung tissue specimens that were implanted subcutaneously into the backs of the mice developed well and remained viable for 20 weeks. Each type of adult human lung epithelial cell showed a different mode of proliferation. Bronchiolar epithelial cells proliferated earlier, with MIB-1 labeling of up to 20% of the cells in the grafts at 8 weeks, while alveolar type II cells proliferated later, with labeling of up to 5% of graft cells at 12 weeks. Conclusion: This model seems to allow adult human lung epithelial regeneration to be investigated in vivo over the long term.
Infrequent Alteration in the p53R2 Gene in Human Transitional Cell Carcinoma of the Urinary Tract
Authors: Hayashi Hideki , Furihata Mutsuo , Kuwahara Morimasa , Kagawa Susumu , Shuin Taro , Ohtsuki Yuji
Published: January 2004

Objective: Functional defects in DNA repair have been shown to be associated with genomic instability followed by cancer. Recently, p53R2 [p53-inducible ribonucleotide reductase (RR) small subunit 2 homologous] was identified as a novel RR gene which is directly regulated by p53 protein in the G1 and G2 phases of the cell cycle supplying nucleotides to repair damaged DNA. Methods: We performed genetic analyses of p53R2 to determine whether p53R2 alterations play significant roles in urothelial tumorigenesis. Genomic DNA from 108 primary transitional cell carcinomas (TCCs; 81 of the urinary bladder and 27 of the renal pelvis or ureter) was analyzed for mutation in the p53R2 gene by direct sequencing. We focused on three domains of the p53R2 gene: one RR small subunit signature involving codons 120–146 (region 1) and two putative nuclear localization signal sequences, involving codons 149–155 (region 2) and codons 163–169 (region 3). In addition, a p53-binding site of 20 nucleotides in intron 1 of p53R2 was also analyzed. Results: One renal pelvic TCC (0.9%: 1/108) had a single-base substitution in p53R2 with a G to T transversion resulting in the amino acid substitution Glu136 → Asp. This base substitution was localized within the domain of exon 4 encoding the RR small subunit signature, and causes an amino acid substitution in one of the most highly conserved regions of p53R2, in which human R2 and yeast RNR2 and RNR4 proteins are highly homologous. Conclusion: This finding provides the in vivo evidence for the infrequent involvement of alterations in p53R2 inhuman urothelial TCCs.
Vascular Gene Expression in Atherosclerotic Plaque-Prone Regions Analyzed by Representational Difference Analysis
Authors: Boräng Stina , Andersson Tove , Thelin Anders , Odeberg Jacob , Lundeberg Joakim
Published: January 2004

Objectives: Atherosclerotic plaques are known to develop and progress where the endothelium is subjected to turbulent blood flow. We have applied cDNA representational difference analysis (RDA) to study vascular gene expression in mouse aorta in a model for atherosclerosis. Methods:Gene expression profiles were investigated in plaque-prone and plaque-resistant localizations in the ascending aorta and arch in 8-week-old ApoE–/– and LDLR–/– mice. Total RNA was extracted and two rounds of subtraction were performed; the difference products were characterized in detail by shotgun cloning and analysis of more than 2,700 gene sequences. Results: The identified differentially expressed gene sequences include both genes with known involvement in vascular gene expression and genes previously not implicated in vascular processes. For example, CD36 and caveolin, previously reported for their participation in the progression of atherosclerosis, were found to have an increased expression in vessel localizations thought to be especially susceptible to plaque formation. Conclusions: This report provides new in vivo information of expressed genes that can be useful for further investigations of the molecular mechanisms in focal localization of atherosclerosis.
Multiple Signal Pathways Are Involved in the Mitogenic Effect of 5(S)-HETE in Human Pancreatic Cancer
Authors: Ding Xian-Zhong , Tong Wei-Gang , Adrian Thomas E.
Published: January 2004

Pancreatic carcinoma is characterized by poor prognosis and lack of response to conventional therapy. The reasons for this are not fully understood. We have reported that inhibition of 5-lipoxygenase abolished proliferation and induced apoptosis in pancreatic cancer cells while the 5-lipoxygenase metabolite, 5(S)-hydroxyeicosatetraenoic acid [5(S)-HETE] stimulated pancreatic cancer cell proliferation. The current study was designed to investigate the underlying mechanisms for 5(S)-HETE-stimulated proliferation of pancreatic cells. Two human pancreatic cancer cell lines, PANC-1 and HPAF, were used. Cell proliferation was monitored by thymidine incorporation and cell counting. Phosphorylation of P42/44MAPK (mitogen activated protein kinase, ERK), MEK (MAPK/ERK kinase), P38 kinase, JNK/SAPK (c-Jun N-terminal kinase/ stress-activated protein kinase), AKT and tyrosine residues of intracellular proteins was measured by Western blot using their corresponding phospho-specific antibodies. The results showed that (1) 5(S)-HETE markedly stimulated pancreatic cancer cell proliferation in a time- and concentration-dependent manner; (2) 5(S)-HETE induced tyrosine phosphorylation of multiple intracellular proteins while the tyrosine kinase inhibitor, genestein, blocked 5(S)-HETE-stimulated cell proliferation; (3) 5(S)-HETE significantly stimulated both MEK and P42/44MAPK phosphorylation and the MEK inhibitors, PD098059 and U0126, inhibited 5(S)-HETE-stimulated proliferation in these two cell lines; (4) 5(S)-HETE also stimulated P38 kinase phosphorylation but the P38 inhibitor, SB203580, did not effect 5(S)-HETE-stimulated cell proliferation; (5) 5(S)-HETE markedly stimulated AKT phosphorylation while the phosphatidylinositide-3 (PI3)-kinase inhibitor, wortmannin, blocked 5(S)-HETE-stimulated cell proliferation; (6) phosphorylation of JNK/SAPK was not induced by 5(S)-HETE, and (7) the general protein kinase C (PKC) inhibitor, GF109203X, did not affect 5(S)-HETE-stimulated cancer cell proliferation. These findings suggest that intracellular tyrosine kinases, MEK/ERK and PI3 kinase/AKT pathways are involved in 5(S)-HETE-stimulated pancreatic cancer cell proliferation but P38 kinase, JNK/SAPK and PKC are not involved in this mitogenic effect.
Rituximab for Treatment of Advanced Extranodal Marginal Zone B Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Raderer Markus , Jäger Gerald , Brugger Stefan , Püspök Andreas , Fiebiger Wolfgang , Drach Johannes , Wotherspoon Andrew , Chott Andreas
Published: January 2004

Background: Extranodal marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) is a relatively common type of lymphoma. Owing to its B cell lineage, it appears to be a potential target for treatment with the CD20 antibody rituximab. We present an analysis of our experience with rituximab for treatment of patients with advanced MALT lymphoma. Patients and Methods: A retrospective analysis of patients with histologically verified MALT lymphoma undergoing treatment with rituximab was done. After reassessment of histological samples for the presence of MALT lymphoma, patients were evaluated as regards date of diagnosis, prior therapy for MALT lymphoma, sites of involvement upon treatment with rituximab, clinical response in terms of complete remission (CR), partial response (PR), stable disease (SD) and progressive disease as well as symptomatic response, duration of response and survival. Results: A total of 9 patients with advanced MALT lymphoma undergoing therapy with single-agent rituximab were identified. All patients received treatment at a dose of 375 mg/m2 once weekly ×4. One patient each had relapsed after chemotherapy and radiation, respectively, while none of the other 7 patients had received prior cytotoxic treatment or radiation. Three patients achieved a CR, 2 patients had PR for 6 and 14 months, while the remaining patients had SD between 8 and 18+ months. One patient died of progressive disease in spite of the initiation of chemotherapy and 1 patient succumbed to a cardiovascular event while having been in ongoing PR for 11 months. The other 7 patients are currently alive with disease 10–27 months after initiation of therapy. Follow-up biopsies for histological assessment were available in 5 patients with gastric lymphoma. In 1 patient with SD, however, persistence of CD20-positive cells within lymphoepithelial lesions was noted in spite of almost complete depletion of B lymphocytes from the normal gastric mucosa, suggesting either recirculation of MALT lymphoma cells to these lesions or defining lymphoepithelial lesions as a sanctuary site from rituximab penetration. Conclusion: Rituximab had only moderate activity in terms of inducing objective responses in our unselected and heterogeneous cohort of patients with disseminated MALT lymphoma. Long-term disease stabilization, however, along with a symptomatic benefit was seen in all patients. Our data nevertheless indicate that rituximab might not optimally penetrate into the gastric mucosa in all patients.
Usefulness of 99mTc-Tetrofosmin Scintigraphy in Different Variants of Kaposi’s Sarcoma
Authors: Spanu A. , Madeddu Gr. , Cottoni F. , Manca A. , Migaleddu V. , Chessa F. , Masala M.V. , Cossu A. , Falchi A. , Mura M.S. , Madeddu G.
Published: January 2004

We investigated 99mTc-tetrofosmin scintigraphy in 27 patients with Kaposi’s sarcoma: 20 had classic (CK), 5 AIDS-associated (AK) and 2 transplantation-associated (TK) variants. Twenty-three patients had clinically evident cutaneous and/or mucosal lesions, 9 of them with associated sarcomatous lymphadenopathy; 2 TK patients had only lymph nodes or other extracutaneous Kaposi sites. Both planar and SPECT 99mTc-tetrofosmin scintigraphies were performed in all cases and neck pinhole (P)-SPECT in selected patients. 99mTc-tetrofosmin uptake was observed in 88% of patients with clinically evident cutaneous and/or extracutaneous Kaposi lesions. Scintigraphy gave additional information on cutaneous lesion extent, particularly SPECT regarding deep invasion and subclinical sites in some cases. However, scintigraphy was less sensitive in the detection of small, isolated and scattered lesions. SPECT/P-SPECT were positive in 8/8 patients with sarcomatous lymph nodes, planar imaging in 5/8, ultrasonography in 7/8, while all procedures were negative in 6 other patients with reactive or HIV infection lymph nodes. SPECT demonstrated lymphadenopathy remission in 1 TK patient after immunosuppressive therapy modification and, like planar imaging, ascertained an associated lymphoma with 67Ga-citrate combined. 99mTc-tetrofosmin scintigraphy, especially SPECT, can be useful both in the detection and staging of Kaposi sarcoma lesions as a complementary tool to clinical and other conventional diagnostic methods.
Role of Mammography, Ultrasound and Large Core Biopsy in the Diagnostic Evaluation of Papillary Breast Lesions
Authors: Puglisi Fabio , Zuiani Chiara , Bazzocchi Massimo , Valent Francesca , Aprile Giuseppe , Pertoldi Barbara , Minisini Alessandro Marco , Cedolini Carla , Londero Viviana , Piga Andrea , Di Loreto Carla
Published: January 2004

Background: It is well recognized that distinguishing benign from malignant papillary lesions of the breast may pose challenging diagnostic problems. To prospectively evaluate the potential role of mammography, ultrasound and image-guided core biopsy in the diagnosis of papillary lesions of the breast. Methods: 1,442 women consecutively underwent 14-gauge core biopsy and in 51 cases (3.5%) a diagnosis of papillary lesion was formulated. Both radiologists and pathologists independently expressed their degree of suspicion of malignancy (not suspicious, low, moderate, high) on the basis of radiological and core biopsy findings, respectively. Surgical excision of the lesion was used as gold standard and diagnostic agreement was assessed by the kappa statistic. Results: At surgery, 19 of the 49 (38.7%) resected cases had a diagnosis of malignancy. A poor agreement was found between mammography and core biopsy results in the categorization of suspicion of malignancy (k = 0.03). Similar data were obtained between ultrasound and core biopsy (k = 0.07). A poor agreement was also observed between radiological and surgical results (k < 0.20). In contrast, a good agreement was found between core biopsy and surgical samples (k > 0.70). However, 5 (26%) out of the 19 malignant cases at surgery were judged as benign or probably benign on core biopsy. Depending on how the categories of suspicion on core biopsy were set up, the range of sensitivity was 74–89%, whereas specificity ranged from 91 to 97%. Conclusions: Image-guided large core biopsy allows for a correct diagnosis in the majority of papillary lesions. However, its sensitivity is not good enough for surgical excision to be avoided.
Impact of Interval Debulking Surgery on Clinical Outcome in Primary Unresectable FIGO Stage IIIc Ovarian Cancer Patients
Authors: Fanfani Francesco , Ferrandina Gabriella , Corrado Giacomo , Fagotti Anna , Zakut Haim Vito , Mancuso Salvatore , Scambia Giovanni
Published: January 2004

Objectives: To report the results of neoadjuvant chemotherapy (NACT) and the impact of interval debulking surgery (IDS) on clinical outcomes of patients considered unresectable at primary surgery. Methods: Retrospective analysis was carried out on 73 consecutive stage IIIc ovarian cancer patients treated with platinum-based NACT followed by IDS. Their clinical outcomes were compared with those of 111 consecutive stage IIIc ovarian cancer patients treated with primary cytoreduction followed by platinum-based adjuvant chemotherapy. Results: Patients who underwent successful IDS had a more favorable prognosis than those who did not in terms of time to progression (TTP) (p = 0.00001), and overall survival (OS) (p = 0.0001). On the other hand, in the group of patients that underwent successful IDS, no differences in survival outcomes were observed between patients with no residual disease and patients with macroscopic residual disease <2 cm after IDS (p = n.s.). Conclusions: NACT followed by successful IDS can achieve good results in terms of survival outcomes in a high percentage of chemoresponsive IIIc ovarian cancer patients classified as unresectable at primary surgery. These results are in fact inferior to those achievable with optimal primary cytoreduction; however, they were quite similar to those seen with suboptimal primary cytoreduction.
Changes in Apoptosis and Mitotic Index, p53 and Ki67 Expression in Various Types of Oral Leukoplakia
Authors: Kövesi György , Szende Béla
Published: January 2004

Introduction: Leukoplakia is the most frequent pre-blastomatous alteration in the oral cavity. Its potential for malignant transformation is unpredictable. The aim of the present study was to provide data about the processes and molecular genetic background of this disease. Materials and Methods: Leukoplakias of 15 patients and oral squamous cell carcinomas of 3 patients treated at the Department of Periodontology and Oral Surgery, Semmelweis University, were studied by histological and immunohistochemical methods. The samples were fixed in 4% formalin and embedded in paraffin. Hematoxylin and eosin staining, TUNEL reaction (Apop-Detect kit), and immunohistochemical reactions for Ki67 and p53 were applied. The severity of dysplasia, the mitotic and apoptotic indices and expression as well as distribution of Ki67 and p53 were examined and compared to the clinical appearance of leukoplakia. Results: The mitotic and apoptotic indices and Ki67 expression increased significantly in parallel with the severity of dysplasia and also with the clinical stage (homogenous, nodular, erythroleukoplakia). The positivity and intracellular localization of (mutant) p53 varied according to the clinical form of leukoplakia. Homogenous and nodular forms showed cytoplasmic staining, while erythroleukoplakia and carcinoma cases were characterized by nuclear positivity. Conclusions: The increased apoptotic and Ki67 indices may indicate an unfavorable prognosis for leukoplakia. The expression of Ki67 and p53 in various forms of leukoplakia point to the increasing instability of the genome in parallel with the severity of leukoplakia.
Low Collagenase-1 (MMP-1) and MT1-MMP Expression Levels Are Favourable Survival Markers in Advanced Colorectal Carcinoma
Authors: Bendardaf R. , Lamlum H. , Vihinen P. , Ristamäki R. , Laine J. , Pyrhönen S.
Published: January 2004

Objective: Extracellular matrix degradation is required for invasive growth and metastasis formation in colorectal carcinoma; therefore, we examined matrix metalloproteinases expression (MMP-1, MMP-13 and MT1-MMP) and apoptosis in tumours from 49 patients with advanced colorectal disease. Methods: MMP expression was determined immunohistochemically and apoptotic index (AI) was ascertained using the TUNEL assay. Results: Low levels of MT1-MMP, MMP-1 and AI were found to be favourable markers significantly associated with longer survival. MT1-MMP expression levels below the median (≤14.0% of tumour cells) were associated with better overall survival (median 26.2 vs. 15.6 months, p = 0.02) and MMP-1 expression levels below the median (≤28.7% of tumour cells) correlated with longer survival following metastasis (median 21.5 vs. 13.3 months, p = 0.05). MT1-MMP, MMP-1 and AI were all found to have significant independent effects on survival. Interestingly, MMP-1 expression levels above the median were associated with distal disease of the colon (p = 0.02). Conclusions: These findings reveal that MT1-MMP and MMP-1 expression levels and AI are useful prognostic indicators in advanced colorectal carcinoma and suggest that markers of MMP expression might be used in identifying patients who would benefit from new treatment modalities involving MMP inhibitors.
The Supplementary Diagnostic Power of Selected Immunohistochemical, Molecular Genetic and Infective Parameters in Epithelial Hyperplastic Laryngeal Lesions
Authors: Kleist Britta , Junghans Dirk , Lorenz Gerd , Bankau Alexander , Poetsch Micaela
Published: January 2004

Objectives: MIB-1 and p53 protein expression, loss of heterozygosity (LOH), microsatellite instability (MSI) of di- and mononucleotide repeats, and HPV status were tested for their potential to characterize different stages of epithelial hyperplastic laryngeal lesions (EHLL). Methods: Thirty-two EHLL were reclassified according to the Ljubljana classification into simple (SH), abnormal (AbH), atypical hyperplasia (AtH) and carcinoma in situ, and investigated by immunohistochemical methods, PCR and direct sequencing analysis. Results: MIB-1 increased with progressive grades of EHLL, whereas p53 protein expression was distinctive only between SH and AbH. LOH showed increasing frequency with grades of the lesions, but the distribution of altered loci (9p, 9q, 10q, 11q, 17p) was not qualified to differentiate between the stages. MSI was detected in SH, AbH and AtH without clear correlation to histopathological grading. HPV infection occurred mostly in SH and AbH (both: 66.7%). Conclusion: MIB-1 labeling and allelic loss could assist histopathological diagnosis in the entire spectrum of EHLL, whereas the MSI results point to a genetic instability of the laryngeal mucosa in general and are therefore not helpful in the distinction of different stages of EHLL. However, future molecular genetic analyses should consider more late events of laryngeal carcinogenesis to improve their diagnostic potential. Furthermore, our results indicate that nonrisky and risky EHLL could probably be caused by different exogenous factors.
Seprase, a Membrane-Type Serine Protease, Has Different Expression Patterns in Intestinal- and Diffuse-Type Gastric Cancer
Authors: Okada Kyoko , Chen Wen-Tien , Iwasa Satoshi , Jin Xin , Yamane Tetsu , Ooi Akishi , Mitsumata Masako
Published: January 2004

Objective: Seprase is an integral membrane serine proteinase with gelatinase activity that may be involved in cancer invasion and metastasis. However, the pathophysiologic significance of its expression in gastric cancer tissue has not been fully elucidated. Methods: Seprase expression and distribution in gastric cancer specimens obtained from 133 patients were examined by immunohistochemistry and immunoblotting. Results: Immunohistochemistry showed that in intestinal-type cancer, which includes well and moderately differentiated adenocarcinoma, seprase immunoreactivity was mainly recognized in the moderately differentiated cells and not in the well differentiated cells. In the diffuse type, which includes poorly differentiated adenocarcinoma and signet ring cell carcinoma, seprase immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The reactive pattern in the cells was different between moderately differentiated adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell membrane also apparently reacted in the former, while only the cytoplasm reacted diffusely in the latter. Seprase immunoreactivity was also recognized in endothelial cells and stromal cells especially adjacent to tumor nests. The immunoreactivity of the stromal cells was more abundant in the intestinal type than in the diffuse type, and these stromal expressions of seprase in the intestinal type correlated with the liver (13/13 = 100% of cases with metastases) or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting showed that the levels of seprase protein were higher in intestinal-type cancer than in diffuse-type cancer. Conclusion: These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer.
Imaging of High-Risk Plaque
Authors: Nemirovsky Dmitry
Published: January 2004

‘High-risk’ or ‘vulnerable’ plaques in the coronary arteries have characteristics that make them more prone to disruption and subsequent thrombosis – the mechanisms of most acute coronary syndromes (ACS). There are a number of imaging modalities that are capable of visualizing these features. This article discusses invasive modalities for identifying ‘high-risk’ plaque such as intravascular ultrasound, coronary angioscopy, optical coherence tomography, near-infrared spectroscopy and coronary thermography. It also discusses the use of noninvasive modalities such as computed tomography MRI and ultrasound. When these imaging modalities are combined with standard cardiac risk factors and more novel markers of systemic inflammation and thrombogenicity we can improve our ability to identify the ‘high-risk’ patient.
Stem Cells for the Heart, Are We There Yet?
Authors: Timmermans F. , De Sutter J. , Gillebert T.C.
Published: January 2004

Although several repair mechanisms have been described in the human heart, all fall too short to prevent clinical heart disease in most acute or chronic pathological cardiac conditions. Moreover, despite many breakthroughs in cardiovascular medicine, the complications of a myocardial infarction such as chronic heart failure remains a serious worldwide problem. Bone marrow stem cells could provide for a promising strategy to restore myocardial infarctions and prevent postinfarct congestive heart failure, because there is growing body of evidence that bone marrow stem cells, such as mesenchymal stem cells, can generate new cardiomyocytes in animals and humans. In this review, we will discuss important issues on stem cell therapy for cardiac regeneration after myocardial infarction, which might be of paramount importance when considering future human trials.
Sudden Cardiac Death in Athletes
Authors: Lorvidhaya Peem , Stephen Huang Shoei K.
Published: January 2004

Sudden cardiac death in athletes, although relatively uncommon, is a well-recognized condition generally associated with some congenital abnormalities. It, however, continues to be of vast interest to the public as athletes are seen as a distinct group of individuals who are especially able to tolerate more intense physical activities than the general population. Obviously, intense activities predispose susceptible athletes to sudden cardiac death, hence the importance of pre-participation screening tests. As the cost of healthcare continues to be on the rise, there will be increasing difficulty justifying a nation-wide method of screening cost-effectively. This article is intended to describe the possible underlying causes of sudden cardiac death discovered thus far, as well as methods for detection, pre-participation guidelines, and emerging therapy.
The ‘Open-Artery Hypothesis’: New Clinical and Pathophysiologic Insights
Authors: Abbate Antonio , Biondi-Zoccai Giuseppe G.L. , Baldi Alfonso , Trani Carlo , Biasucci Luigi M. , Vetrovec George W.
Published: January 2004

The open-artery hypothesis states that myocardial reperfusion, even if late for myocardial salvage, provides benefits and prevents adverse cardiac remodeling. While observational data in humans regarding the deleterious impact of a permanent infarct-related artery occlusion and the benefits of spontaneous reperfusion are quite consistent, the reports regarding late revascularization are inconclusive in order to prove such a hypothesis. The observational studies tend to have selection biases, while randomized trials to date are too small to be conclusive. Moreover, the pathophysiological mechanisms underlying presumed benefits of reperfusion are still unclear. However, although the open-artery hypothesis remains unproven, the current evidence suggesting benefits calls for additional studies. Limitations of ischemic left ventricular dilatation and myopathy could markedly reduce cardiovascular morbidity and mortality after acute myocardial infarction.
Functional Capacity Impairment in Patients with Coronary Artery Disease: Prevalence, Risk Factors and Prognosis
Authors: Tenenbaum Alexander , Motro Michael , Fisman Enrique Z. , Leor Jonathan , Boyko Valentina , Mandelzweig Lori , Behar Solomon
Published: January 2004

Background: Some patients developing heart failure and functional capacity impairment have no history of myocardial infarction (MI), and stable angina pectoris is their principal clinical manifestation of coronary artery disease (CAD). The present study was aimed to evaluate the outcome of CAD-related functional capacity impairment in patients with and without a history of MI over a 7.7-year follow-up. Methods: The study sample comprised 14,283 coronary patients aged 45–74 years, screened for participation in the Bezafibrate Infarction Prevention study. The presence of NYHA functional class II was defined as mild functional capacity impairment and the presence of NYHA functional class III–IV was defined as advanced functional capacity impairment. Results: The patients were divided in two groups: (1) those with a history of MI, 10,307 patients, who formed three subgroups: NYHA I 7,551 patients (73.3%); NYHA II 2,176 patients (21.1%); NYHA III + IV 580 patients (5.6%), and (2) those without a history of MI, 3,976 patients, who also formed three subgroups: NYHA I 2,744 patients (69.0%); NYHA 981 patients (24.7%); NYHA III + IV 251 patients (6.3%). Multivariate analysis identified a history of MI as a consistent predictor of increased all-cause and cardiac mortality for patients with NYHA I, II and III + IV subgroups with escalating significance for patients with advanced functional capacity impairment: hazard ratios of 1.55 (95% CI 1.36–1.75), 1.56 (95% CI 1.30–1.86) and 1.72 (95% CI 1.24–2.40) for all-cause and 1.93 (95% CI 1.60–2.33), 1.73 (95% 1.35–2.20) and 3.22 (95% CI 1.87–5.54) for cardiac mortality, respectively. Conclusions: The prevalence of low functional capacity is similar among coronary patients with and without a history of MI, but their long-term survival differs substantially in favor of the latter. Therefore, two different types of CAD-related advanced functional capacity impairments (post-MI and non-post-MI) can be distinguished.
Visualizing T Cell Migration in vivo
Authors: Iparraguirre Amaya , Weninger Wolfgang
Published: January 2004

Ever since the realization that T lymphocytes are key players in the defense against pathogens and tumors, a major aim of immunologists has been to understand the relationship between the functional and migratory properties of antigen-specific T cells. The current paradigm proposes that T cells follow organ-specific trafficking pathways to exit from blood into the extravascular compartment. T cell homing is regulated at the level of adhesion molecules and chemokine receptors, whose expression is linked tightly to the differentiation state of the cell. Naïve T lymphocytes follow relatively uniform recirculation routes through secondary lymphoid organs, the molecular cues of which are fairly well understood. As effector and memory T cells must be capable of reaching virtually any site in the body, their migratory behavior is considerably more heterogeneous. During the past few years, innovative approaches for tracking T cells in vivo have emerged. Here, we review recent technical developments in experimental methods for the visualization of T cells both at the population and single cell level in vivo, and discuss what these methods have taught us about T cell trafficking.
Immunotherapy of Malignant Diseases
Authors: Ko Eric C. , Wang Xinhui , Ferrone Soldano
Published: January 2004

In recent years, there has been growing interest in the application of immunotherapy as an alternative to chemotherapy and radiotherapy for the treatment of malignant diseases. This interest is due to a variety of factors, including revival of the immunosurveillance theory, availability of well-defined and structurally characterized human tumor-associated antigens (TAAs), progress in our understanding of the molecular pathways required for induction and maintenance of an immune response, and advances in methodologies to generate TAA-specific cytotoxic T lymphocytes (CTLs) and monoclonal antibodies (mAbs) as immunological probes. However, contrary to the positive results obtained with TAA-specific immunotherapy in animal model systems, the clinical response in patients has been disappointing. Frequently, the immune responses do not correlate with the clinical responses. Analysis of the underlying mechanisms of this dichotomy have identified the low immunogenicity of TAAs, the lack of immunological markers to predict clinical outcomes, and the ability of tumors to escape immune recognition and destruction as challenges to the development and application of immunotherapy. In this paper, we have reviewed the mechanisms underlying immune unresponsiveness to TAAs and strategies to overcome this unresponsiveness in the humoral and cellular immune responses, highlighting findings from different antigenic systems to prove the validity of these strategies. Additionally, we have addressed limitations to TAA-targeting immunotherapy as a result of the genetic instability of tumor cells, and have discussed strategies to overcome this limitation by targeting immunotherapy to molecules implicated in tumor-associated angiogenesis. Lastly, we have concluded by indicating the need to refine the implementation of clinical trials of immunotherapy, and to emphasize combination therapies to counteract the multiple tumor escape mechanisms.
Increased Levels of IL-2 and IL-4 in Stimulated Adenoidal Lymphocytes of Atopic Children
Authors: Papatziamos Georgios , van Hage-Hamsten Marianne , Halden Gunilla , Lundahl Joachim , Hemlin Claes
Published: January 2004

Background: The adenoid is involved in the defence against airway pathogens and its surface is also exposed to airborne allergens. The knowledge about reactions taking place in the lymphatic tissue of this organ is, however, limited. To elucidate the influence of atopy we investigated the cellular and cytokine profile of in vitro-stimulated adenoid lymphocytes. Methods: Adenoid tissue cells from 13 atopic and 8 non-atopic children were cultured and stimulated with ionomycin and 4β-phorbol 12-myristate 13-acetate. Supernatants were collected after 4 and 20 h of stimulation and interleukin-2 (IL-2), IL-4 and interferon-γ (IFN-γ) were analysed by ELISA. Flow cytometry was used to quantify the leukocyte markers CD3, CD19, CD25 and HLA-DR. Results: Increased levels of IL-2 and IL-4 but not IFN-γ were detected in the supernatants of adenoid cell cultures from atopic children after 20 h of stimulation (p < 0.05) and a significant correlation with a positive regression between IL-2 and IL-4 was found. Atopy was also associated with a greater increase in the percentage of CD19-positive B cells after stimulation (p < 0.05). Conclusions: A difference in the reactivity of adenoidal lymphoid cells in children was observed between atopic and non-atopic subjects. Atopy was associated with an increased production of IL-2 and IL-4 as well as a more pronounced increase of B cells.
A Novel Mouse Model of Experimental Asthma
Authors: Sarpong Sampson B. , Zhang Liu-Yi , Kleeberger Steven R.
Published: January 2004

Background: Animal models that mimic the pulmonary features observed in human asthma are important tools to study the mechanism(s) of allergen-induced asthma. Cockroach and dust mite allergens are two common allergens found in the ‘inner city’ environment. In this study, we examined the interaction between recombinant cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain (A/J). The tested hypothesis was that there are enhanced effects of exposure to r Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice. Methods: Five groups of mice (male, 6–8 weeks) were examined: vehicle (saline) controls; adjuvant (alum) controls; r Bla g 2 immunized (0.01–10 µg/mouse), r Der f 1 immunized (0.01–10 µg/mouse), and combined immunization with r Der f 1 (0.05 µg/mouse) and r Bla g 2 (0.0 5 µg/mouse). Mice were immunized at days 0 and 7, challenged by oro-tracheal inhalation with r Der f 1 and/or r Bla g 2 allergen at day 14, and were studied and sacrificed on day 17. Airway hyperreactivity was measured by peak airway pressure and airway pressure time index (APTI). Differential cell analysis and total proteins in bronchoalveolar lavage returns were used to assess airway inflammation and epithelial injury. Results: Dose-related statistically significant increases in peak pressure, APTI, total cells, eosinophils, epithelial cells, but not total proteins, were induced by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose-related increases in airway total cells, eosinophils, epithelial cells and total proteins were observed in r Der f 1 immunized mice. Compared to either allergen alone, enhanced airway inflammation and epithelial damage, but not airway reactivity, were detected in the combined group. Conclusion: This novel mouse model will allow investigation of the immunopathogenesis of human asthma and should provide insight into the common form of ‘inner city asthma’.