bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory evaluation of two bioenergetics models applied to yellow perch: identification of a major source of systematic error
Authors: Bajer P. G. , Whitledge G. W. , Hayward R. S. , Zweifel R. D.
Published: March 2003

Laboratory growth and food consumption data for two size classes of age 2 year yellow perch Perca flavescens, each fed on two distinct feeding schedules at 21° C, were used to evaluate the abilities of the Wisconsin (WI) and Karas–Thoresson (KT) bioenergetics models to predict fish growth and cumulative consumption. Neither model exhibited consistently better performance for predicting fish body masses across all four fish size and feeding regime combinations. Results indicated deficiencies in estimates of resting routine metabolism by both models. Both the WI and KT models exhibited errors for predicting growth rates, which were strongly correlated with food consumption rate. Consumption‐dependent prediction errors may be common in bioenergetics models and are probably the result of deficiencies in parameter values or assumptions within the models for calculating energy costs of specific dynamic action, feeding activity metabolism or egestion and excretion. Inter‐model differences in growth and consumption predictions were primarily the result of differences in egestion and excretion costs calculated by the two models. The results highlighted the potential importance of parameters describing egestion and excretion costs to the accuracy of bioenergetics model predictions, even though bioenergetics models are generally regarded as being insensitive to these parameters. The findings strongly emphasize the utility and necessity of performing laboratory evaluations of all bioenergetics models for assurance of model accuracy and for facilitation of model refinement.
Increased endothelin in infants of pre‐eclamptic mothers
Authors: Narin Nazmi , Narin Figen , Tutus Ahmet , Tayyar Mehmet
Published: March 2003

Abstract
Objective
: Endothelin (ET), a vasoactive mediator, like others which originate from the endothelium or circulating cells, may participate in myocardial injury. In full‐term neonates of mild pre‐eclamptic mothers (NMPM), it identifies minor myocardial damage missed by other biochemical markers. The present study was designed to determine the diagnostic value of ET concentrations in NMPM.

Methods
: Seventeen NMPM were studied (10 boys and seven girls), and 17 healthy full‐term (nine boys and eight girls) were selected for a control group. Birthweights in NMPM and control group were 2950 g (2.300−3.850) and 3.350 g (2.650−4.000), respectively. The ET measured by the radioimmunoassay method, Troponin T (TnT) were measured by enzyme‐linked immunosorbent assay method and creatine kinase (CK‐MB) determined in chemical 1 analysis.

Results
: Serum ET and TnT concentrations in NMPM (3.32 pg/mL vs 0.74 ng/mL) were significantly higher than the control group (0.82 pg/mL vs 0.10 ng/mL) (P < 0.01 and < 0.001).

Conclusion
: Our study demonstrated high levels of ET, cardiac TnT in NMPM, presumably associated with myocardial damage in NMPM.
Intrauterine treatment for an acardiac twin with alcohol injection into the umbilical artery
Authors: Tongsong Theera , Wanapirak Chanane , Sirichotiyakul Supatra , Chanprapaph Pharuhas
Published: March 2003

An acardiac twin is a unique complication of monochorionic twinning, in which a normal pump twin perfuses the acardiac twin. The mortality rate of the pump twin is greater than 50%. Herein we present the successful treatment of an acardiac twin with alcoholization as follows. An acardiac twin was diagnosed at 24 weeks gestation. Circulation interruption of the acardiac twin was successfully achieved by injection of absolute alcohol (5 mL) into the intra‐abdominal umbilical artery. Serial ultrasound after the procedure revealed normal growth of the pump twin, whereas the acardiac twin was shrinking. Spontaneous premature delivery at 34 weeks gestation resulted in a normal surviving female baby weighing 2410 g and an acardiac female fetus weighing 300 g. This experience suggests that this simple technique may be an alternative treatment for an acardiac twin.
Effect of maternal oral hydration on amniotic fluid index in women with pregnancy‐induced hypertension
Authors: Malhotra Bhawna , Deka Deepika
Published: March 2003

Objective: To evaluate the effect of maternal oral hydration on amniotic fluid index (AFI) in women with pregnancy‐induced hypertension.

Methods: Five women with pregnancy‐induced hypertension and five normotensive gravidae at 32–37 weeks gestation with normal AFI (8–18 cm) were hydrated by oral intake of 2 L of water over 1 h. Both groups were similar in age, parity and gestation. Repeat AFI was measured in all women after 3 h. The differences between pre‐ and post‐hydration AFI in the two groups were analyzed with Student's t‐test for statistical significance.

Results: Maternal oral hydration resulted in a significant increase in AFI in both hypertensive and normotensive gravidae (1.7 cm and 3.48 cm, respectively). However, the extent of increase was significantly lower in the hypertensive group (P = 0.03).

Conclusion: Pregnancy‐induced hypertension adversely affects the increase in amniotic fluid volume with maternal hydration. This observation is of clinical relevance in the management of oligohydramnios associated with pregnancy‐induced hypertension.
Adenovirus‐mediated tissue‐specific cytosine deaminase gene therapy for human hepatocellular carcinoma with different AFP expression levels
Authors: Huang Xin , Zhang Weiping , Wakimoto Hiroaki , Hamada Hirofumi , Cao Xuetao
Published: March 2003

To evaluate whether in vitro and in vivo transferring of Escherichia coli cytosine deaminase gene to a solid tumor will confer the sensitivity to the prodrug 5‐fluorocytosine (5FC) on these cells, we constructed two replication‐defective adenovirus vector in which the cytosine deaminase gene was driven by CAG promoter (Adex1CACD) and AFP gene 5′‐flanking region (Adex1AFPCD), respectively. By transferring these two vectors to SMMC7721AFP(−) and HepG2 human hepatocellular carcinoma (HCC) cells in vitro, we found that Adex1CACD vector could effectively suppress SMMC7721AFP(−) and HepG2 cells growing in the presence of 5FC even if the infected cell is less to 20%, while Adex1AFPCD vector only conferred HepG2 cells sensitivity to 5FC. When Adex1CACD was directly injected into established subcutaneous SMMC7721AFP(−) tumors in nude mice receiving 5FC, the tumor growth was inhibited significantly, which was consistent with those in vitro results. Furthermore, the Adex1AFPCD plus 5FC suppressed SMMC7721AFP(+) tumor growth in vivo, but not SMMC7721AFP(−) tumor. The results suggested that the CAG promoter‐controlled CD gene could effectively mediate the growth inhibition in different kinds of HCC combined with administration of 5FC, and the AFP promoter‐controlled CD gene could only suppress the HCCs expressing high levels of AFP. Therefore, adenovirus‐mediated tumor‐specific gene transfer may be a potential strategy for local control of tumor growth.
Src protein kinase pp60c‐src influences adhesion stabilization of HT‐29 colon carcinoma cells to extracellular matrix components under dynamic conditions of laminar flow
Authors: Haier Jörg , Gallick Garry E. , Nicolson Garth L.
Published: March 2003

Tumor cell adhesion to extracellular matrix (ECM) and its stabilization are important determinants in metastasis formation, and they are mediated, in part, by integrins and regulated by a variety of protein kinases. Protein tyrosine kinase pp60c‐src is found in adhesion‐dependent focal adhesion plaques where it may regulate different integrin‐mediated signaling cascades. Using human HT‐29 colon carcinoma cells stably transfected with pp60c‐src–specific antisense oligonucleotides (HT‐29AS15), we investigated the role of pp60c‐src in integrin‐mediated adhesion and its stabilization to ECM components collagen I or IV under static and laminar fluid flow conditions. Under static adhesion conditions transfection of pp60c‐src antisense oligonucleotides did not modify adhesive properties. Phosphorylation of focal adhesion kinase (FAK) and paxillin induced by static adhesion to collagen I or IV were similar in HT‐29P and HT‐29AS15 cells. However, using hydrodynamic conditions in a laminar flow chamber we found a slight reduction in early adhesion events and an even greater difference in adhesion stabilization rates (ASRs). The transfected cells showed a significant reduction in their ability to withstand shear forces and stabilize adhesive bounds. These changes correlated with the cellular expression levels of pp60c‐src. Our results suggest that pp60c‐src may be involved in stabilization of dynamic HT‐29 cell adhesion to ECM components, and this kinase appears to be part of a mechanosensory protein complex during integrin‐mediated cell adhesion.
Early signalling events in the Avr9/Cf‐9‐dependent plant defence response
Authors: Romeis Tina , Tang Saijun , Hammond‐Kosack Kim , Piedras Pedro , Blatt Mike , Jones Jonathan D. G.
Published: March 2003

Resistance of tomato to the leaf mould fungus Cladosporium fulvum is controlled by the interaction between a plant‐encoded resistance gene (Cf‐9) and pathogen‐encoded avirulence (Avr9) gene. Our objective is to understand the underlying molecular mechanisms that transmit the Cf‐9/Avr9‐dependent pathogen perception event and activate the plant defence response. Our approach toward the understanding of Cf‐function is based on the analysis of early Cf‐9/Avr9‐mediated responses and signalling events. Because Cf‐9 transgenically expressed in tobacco retains its specificity and activity to the Avr9 elicitor, signalling experiments were conducted in the heterologous system using these transgenic lines or derived Cf9 tobacco cell cultures.

Among the earliest responses to the Avr9/Cf‐9 elicitation event were rapid changes in ion‐fluxes, the synthesis of active oxygen species (AOS), probably catalysed by a plant NADPH‐oxidase, and the transient activation of two MAP kinases. These kinases were identified as WIPK (wounding‐induced protein kinase) and SIPK (salicylic‐acid induced kinase) from tobacco. Studies with pharmacological inhibitors suggested that the MAP kinases are located in an independent signalling pathway from the Avr9/Cf‐9‐dependent synthesis of AOS. SIPK and WIPK were involved in pathogen‐related elicitation processes as well as in abiotic stress responses. This indicates that the plant defence is triggered via a signalling network that shares components with pathways originating from abiotic environmental stress stimuli.
Infection of Arabidopsis thaliana leaves with Albugo candida (white blister rust) causes a reprogramming of host metabolism
Authors: Chou Hsueh‐Mei , Bundock Nicholas , Rolfe Stephen A. , Scholes Julie D.
Published: March 2003

Albugo candida (Pers.) (O.) Kunze is a biotrophic pathogen which infects the crucifer Arabidopsis thaliana (L.) Heynh forming discrete areas of infection. Eight days after inoculation of leaves, white blisters became visible on the under surface of the leaf although no symptoms were apparent on the upper surface. By day 14, the region of leaf invaded by fungal mycelium had become chlorotic. Recently it has been hypothesized that an accumulation of soluble carbohydrates, following an increase in invertase activity, may trigger sugar signal transduction pathways leading to the repression of photosynthetic gene expression and to the induction of defence proteins. This hypothesis was investigated by quantifying localized changes in carbohydrate and photosynthetic metabolism and the expression of genes encoding photosynthetic and defence proteins. Quantitative imaging of chlorophyll fluorescence revealed that the rate of photosynthesis declined progressively in the invaded regions of the leaf. However, in uninfected regions of the infected leaf the rate of photosynthesis was similar to that measured in the control leaf until late on during the infection cycle when it declined. Images of nonphotochemical fluorescence quenching (NPQ) suggested that the capacity of the Calvin cycle had been reduced in infected regions and that there was a complex metabolic heterogeneity within the infected leaf. A. candida also caused localized changes in the carbohydrate metabolism of the leaf; soluble carbohydrates accumulated in the infected region whereas the amount of starch declined. The reverse was seen in uninfected regions of the infected leaf; carbohydrates did not accumulate until late on during infection and the amount of starch increased as the infection progressed. There was an increase in the activity of invertases which was confined to regions of the leaf invaded by the fungal mycelium. The increase in apoplastic invertase activity was of host origin, as mRNA levels of the ATβFRUCT1 gene (measured by semiquantitative RT‐PCR) increased 40‐fold in the infected region. The increase in soluble invertase activity resulted from the appearance of a new isoform in the invaded region of the leaf. Current evidence suggests that this was of fungal origin. Northern blot analysis of cab and rbcS showed that photosynthetic gene expression was repressed in the infected leaf from 6 days after inoculation (DAI) when compared to control leaves. In contrast, there was no detectable induction of defence proteins in the infected leaf. These data are discussed in the context of the sugar‐sensing hypothesis presented above.
Differential expression of two Blumeria graminis chitin synthase genes
Authors: Zhang Ziguo , Hall Alison , Perfect Emma , Gurr Sarah J.
Published: March 2003

Two Blumeria graminis chitin synthase genes, designated BgChs1 and BgChs2 were cloned and characterized following the synthesis and use of degenerate PCR primers designed to the conserved regions of fungal chitin synthase (Chs) genes. Their sequences revealed high similarity with the Chs genes previously cloned from other fungi and placed BgChs1 and BgChs2 with the classes I and V, respectively. Each gene was present as a single copy within the barley powdery mildew genome. Semi‐quantitative RT‐PCR assays revealed BgChs1 to be up‐regulated at both the primary germ tube (PGT) and appressorial germ tube (AGT) stages of differentiation whilst the BgChs2 transcript was up‐regulated at the PGT stage. The B. graminisβ‐tubulin gene was used as a control for all RT‐PCR reactions. The BgChs1 transcript was some 30 fold less abundant than the β‐tubulin transcript and BgChs2 was some 30 fold rarer than the BgChs1 transcript. The effects of the chitin substrate analogues nikkomycin Z and polyoxin D on conidial morphogenesis were assessed. These nucleoside peptide inhibitors did not affect germination but both polyoxin D and nikkomycin Z treatment led to a large population of abnormally swollen ‘balloon‐shaped’ AGTs, whilst by 12 h after inoculation polyoxin treatment caused the swollen germ tubes to burst.
Cloning and characterization of a glutathione S‐transferase homologue from the plant pathogenic fungus Botrytis cinerea‡
Authors: Prins Theo W. , Wagemakers Lia , Schouten Alexander , Van Kan Jan A. L.
Published: March 2003

A gene was cloned from Botrytis cinerea that encodes a protein homologous to glutathione S‐transferase (GST). The gene, denominated Bcgst1, is present in a single copy and represents the first example of such a gene from a filamentous fungus. The biochemical function of GSTs is to conjugate toxic compounds to glutathione, thereby detoxifying the compound. In many other organisms, GST plays a role in chemical stress tolerance. We anticipated that GST functions for B. cinerea as a potential virulence factor, enabling the fungus to tolerate fungitoxic plant defence compounds. The expression of Bcgst1 mRNA under various presumably stressful conditions was investigated. Bcgst1 mRNA is expressed at a basal level in liquid cultures and is induced upon addition of hydrogen peroxide to the medium. The level of Bcgst1 mRNA expression during infection of tomato leaves parallels the level of actin mRNA. The role of the Bcgst1 gene in the virulence of Botrytis cinerea was evaluated by constructing gene disruption mutants. Three independent disruption mutants were obtained. The virulence of two mutants on tomato leaves was evaluated. Neither of the mutants showed a decrease in virulence, indicating that the Bcgst1 gene is not essential for virulence on tomato leaves under the conditions tested.
The distribution and expression of a biotrophy‐related gene,CIH1, within the genusColletotrichum
Authors: Perfect Sarah E. , Pixton Katherine L. , O’Connell Richard J. , Green Jonathan R.
Published: March 2003

During the biotrophic phase of the infection process of the hemibiotrophic anthracnose fungusColletotrichum lindemuthianum, an intracellular hypha develops within epidermal cells of its host,Phaseolus vulgaris. This is followed by the formation of secondary hyphae during the necrotrophic phase. Previous work using a monoclonal antibody, UB25, has identified a glycoprotein that is specific to the interfacial matrix that forms between the wall of the intracellular hypha and the invaginated host plasma membrane. The gene encoding the protein identified by UB25 was cloned by immunoscreening and designatedCIH1. The predicted amino acid sequence revealed a proline‐rich glycoprotein, and biochemical evidence suggested that it formed a cross‐linked structure at the biotrophic interface. AlthoughCIH1is a fungal gene, its product has several similarities to plant cell wall proteins. In this paper, we have surveyed the distribution and expression ofCIH1within the genusColletotrichum, encompassing both necrotrophic and hemibiotrophic species. The results show that homologues of theCIH1gene are present in all theColletotrichumspecies tested. Northern blot studies of the time course of the infection processin plantahave shown thatCIH1is expressed by bothC. lindemuthianumin bean andC. trifoliiin alfalfa during the biotrophic phase of fungal development. Immunofluorescence labelling of infected epidermal strips with UB25 revealed that the intracellular hyphae formed byC. destructivumas it infects alfalfa were specifically labelled in a similar way to those formed byC. lindemuthianumin bean. Northern and Western analysis showed thatCIH1was also expressed byC. lindemuthianum in vitro, though not constitutively. Overall, the evidence supports a role forCIH1in biotrophy within the genusColletotrichum.
Up‐regulation of the ascorbate‐dependent antioxidative system in barley leaves during powdery mildew infection
Authors: Burhenne Kim , Gregersen Per L.
Published: March 2003

The ascorbate‐dependent antioxidative system was studied in leaves of barley infected with the barley powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh). Increased ascorbate peroxidase (APX) activity was detected upon infection, especially in the compatible interaction. APX activity was determined in epidermal and total leaf tissues. A relatively higher increase in APX activity was found in the epidermis compared to total leaf 72 h after inoculation in the compatible interaction, but the increase was not restricted to the epidermis. Activity assays in native gels and Northern blot hybridization indicated that the increase in APX activity was caused by a cytosolic APX isoform. ‘Inverse Northern blot’ hybridization results with the cDNA of a cytosolic APX supported the relatively higher increase in epidermal APX activity compared to total leaf activity. In the compatible interaction, monodehydroascorbate reductase (MDHAR) activity increased in temporal and spatial patterns similar to that of APX activity. In contrast to this, dehydroascorbate reductase and glutathione reductase activities either decreased or were unaffected by Bgh infection. The increase in APX and MDHAR activities in the compatible interaction continued until severe infection of the leaves. Thus, an up‐regulation of the antioxidative system of the host cells could play a role for maintenance of the biotrophic relationship between Bgh and the barley leaf by preventing proliferating oxidative processes, which would otherwise be harmful to the living plant cell on which the biotrophic powdery mildew fungus depends.
Methionine synthase, a gene required for methionine synthesis, is expressed in planta by Cladosporium fulvum
Authors: Solomon Peter S. , Nielsen Peter Stein , Clark Anthony J. , Oliver Richard P.
Published: March 2003

The nutritional requirements of phytopathogenic fungi growing in planta has to date been largely ignored. We have begun to address this problem by investigating the methionine requirement for the biotrophic pathogen of tomato Cladosporium fulvum during infection. The Met6 gene from Cladosporium fulvum encoding a cobalamin‐independent 5‐methyltetrahydropteroyltriglutamate‐homocysteinemethyltransferase, was cloned by functional yeast complementation. The open reading frame was found to be 2304 bp, containing no introns and encoding a protein of 87 kDa. In vitro Northern analysis demonstrated high levels of Met6 expression in the absence of externally supplied methionine. However in the presence of methionine or in the absence of carbon, expression of Met6 decreased significantly. Analysis of Met6 expression in planta revealed a strong increase during infection suggesting the requirement for methionine synthesis in planta by Cladosporium fulvum. This study demonstrates that Cladosporium fulvum is starving for methionine during infection and thus implies the essentiality of primary biosynthetic pathways to the infecting fungus.
Characterization of Phytophthora infestans genes regulated during the interaction with potato
Authors: Beyer Katinka , Jiménez Sonia Jiménez , Randall Thomas A. , Lam Stephen , Binder Andres , Boller Thomas , Collinge Margaret A.
Published: March 2003

Suppression Subtractive Hybridization (SSH) was used to search for genes of Phytophthora infestans that are induced during the infection of potato. To avoid having to distinguish the genes of the pathogen from the plant genes involved in defence responses and to isolate the genes involved in the early stages of interaction, mycelium of P. infestans was induced by contact with the host plant and then separated from the plant tissue. A differential cDNA library was generated by SSH that compared such induced mycelium with mycelium incubated in water. The expression of about 100 cDNA fragments from this differential cDNA library was analysed by hybridization of the arrayed PCR products with mRNA from control and induced mycelium. Twenty per cent of them showed increased transcript levels in mycelium within the first 24 h after exposure to a potato leaf. For six of these cDNA clones the elevated expression in response to the potato leaf could be proven by RNA gel blot analysis. Five of these cDNA clones have predicted amino acid sequence homologies to entries in the databases, including an amino acid transporter, a sucrose transporter, a spliceosome‐associated factor, an ABC transporter, and a cell division control protein. We showed that the genes corresponding to these six cDNA clones are differentially regulated during their life. Reliable gene expression analysis of Phytophthora in infected leaf tissue is not possible until c. 48 h post‐infection, but for two of the genes we identified, induction during in planta growth was detectable by RNA gel blot analysis. Therefore the SSH library that we have created provides a basis for the identification of P. infestans genes that are up‐regulated during the interaction with the plant, which could be important for pathogenicity.
Making the case to fund networked access to electronic information services
Authors: COX JOHN
Published: March 2003

The establishment of a local area network can greatly widen access to an organization's electronic information services, create improved conditions for staffing the delivery of these services and improve training and user support. Such a project is, however, expensive to fund. This article describes the approach taken at the Royal Free Hospital School of Medicine to secure funds for networking MEDLINE on hard disk and other information services. The importance of close collaboration between library and computer departments in planning and promoting a project of this nature is emphasized.
Preparing for PREP: the impact of changes in continuing education for nurses on library provision of journals and current‐awareness services: a case study
Authors: CRANE SOPHIE , URQUHART CHRISTINE
Published: March 2003

A survey of 5% of the trained nursing staff in Plymouth was carried out in late 1992/early 1993 to obtain information on professional development preferences, the value of journals read and methods used to obtain access to journals. Results from the structured interview suggested that most of the Plymouth staff would exceed the minimum number of study days (5 days over 3 years) proposed by the UKCC for PREP. Attending a study day was the most popular method of updating clinical knowledge, and the most popular combination of learning styles was a study day, backed up by further reading. Reading of journals was selective, most staff reading only the articles of interest to them personally. Journals with a strong clinical/technical orientation were valued. Few units were planning new journal subscriptions. The concept of an SDI service was popular, though subjects selected were often general, and frequently multidisciplinary. Recommendations concerned the provision of a library back‐up service for study days, preparation of a self‐access open learning package, and review of specialized information services.
Editorial—Evidence‐based practice: new opportunities for librarians
Authors: HAINES MARGARET
Published: March 2003

A new paradigm for medical practice is emerging. Evidence‐based medicine de‐emphasizes intuition, unsystematic clinical experience, and pathophysiological rationale as sufficient grounds for clinical decision making and stresses the examination of evidence from clinical research. Evidence‐based medicine requires new skills of the physician, including efficient literature searching and the application of formal rules of evidence evaluating the clinical literature.1
From intelligence to evidence‐based healthcare: a purchasing odyssey
Authors: BOOTH ANDREW , HEY SUE
Published: March 2003

Since the appearance of the NHS Executive's guidance document, Purchasing Intelligence (1991), efforts have been concentrated on the development of ‘purchasing intelligence facilities’ staffed, in the main, by health librarians. However, the concept of ‘intelligence’ has a wider dimension that impacts upon the whole culture of an organization. The authors examine purchasing organizations against popular theories of organizational development. The characteristics of Handy's Task culture, with Athena as its patron, may be observed in many authorities. Using the results of two surveys, conducted in March 1995, they identify some key information management issues involving structure, tasks, technology and people. Skills in information ‘transformation’ must be acquired by all staff in purchasing authorities. The intelligence officer must become a modern‐day Odysseus if the intelligence facility is to ‘survive and thrive’.
A Delphi survey of research priorities and identified areas for collaborative research in health sector library and information services UK
Authors: Dwyer Maureen
Published: March 2003

The survey aims were to determine research priorities in the Health Library and Information Services sector in the United Kingdom as to their perceived value for the professional and impact on user needs and to identify areas suitable for collaborative research.

A 34‐member panel consisting of the Chairs of professional groups, journal editors, educationalists, key organizations and representatives from the Health Libraries Group, Libraries for Nursing and University Health Science Libraries professional groups, participated in a three‐round postal questionnaire survey using the Delphi Technique.

Consensus was achieved for a final set of 20 research priorities. The priorities and their category groups are discussed in the context of (i) the current R&D scene, and (ii) the health information environment. Six developmental recommendations are provided.
Medical information provision in Seychelles: development, current state and future focus
Authors: Stokes Peter John
Published: March 2003

Medical information in Seychelles is provided by a library and documentation unit within the Ministry of Health. This unit has been in operation for 10 years and during this time has expanded in the number and type of services provided. This short report describes the current situation at the library and the vision for the next 10 years.
Congenital acinar dysplasia: a rare cause of pulmonary hypoplasia
Authors: Davidson  , Batman  , Fagan
Published: March 2003

Aims:

To describe a third case of congenital pulmonary acinar dysplasia, comparing its clinicopathological features with those of the two previous cases and with cystic adenomatoid malformations.

Methods and results:

An externally normal female infant was born to a 25‐year‐old after a normal pregnancy. Ventilation was not established. At autopsy the hypoplastic lungs showed bronchial development but no acinar development, resembling the pseudoglandular phase of 16 weeks gestation. As in the previous cases the infant was female, born at term with unaffected older sibling(s); however, no intrapulmonary haematopoietic tissue was identified in the present case. Cystic adenomatoid malformations also resemble microscopically the pseudoglandular phase but are focal pulmonary hyperplasias rather than generalized pulmonary hypoplasias.

Conclusion:

Congenital acinar dysplasia is a rare, apparently sporadic lethal developmental defect resulting in pulmonary hypoplasia due to failure of lung development beyond the pseudoglandular phase seen at 16 weeks gestation.
Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study of 15 cases
Authors: Li  , Kitano  , Chen  , Itoh  , Kawashima  , Sugihara  , Nozoe  , Mimura
Published: March 2003

Aims:

Intraosseous jaw cysts with a solely orthokeratinized lining epithelium have been suggested to differ from the typical odontogenic keratocysts (OKC) by exhibiting a less aggressive behaviour. We report 15 cases of such cyst type under the term of ‘orthokeratinized odontogenic cyst (OOC)’ and compared their clinical, histological and immunocytochemical features with that of OKC.

Methods and results:

The cysts of the present series were all solitary lesions, occurred mostly in young male patients, and showed a predilection for the posterior mandible areas. Follow‐up of 14 patients, nine of whom were treated by simple enucleation, revealed no recurrence over a period of 3.5–12 years after surgery. None of the patients had any association with the naevoid basal cell carcinoma syndrome. Furthermore, histological and immunocytochemical comparison between OOC and OKC revealed marked differences in their morphology and epithelial expression. The lining epithelium of OOC lacked the typical features of OKC and appeared to show a lower proliferative activity.

Conclusion:

These findings suggest that OOC is clinicopathologically separate from other types of odontogenic cysts and may thus constitute a distinct clinical entity.
Primary intestinal gamma‐delta T‐cell lymphoma with evidence of Epstein–Barr virus
Authors: Lavergne  , Brochériou  , Delfau  , Copie‐Bergman  , Houdart  , Gaulard
Published: March 2003

Aims:

Primary intestinal T‐cell lymphomas account for about 5% of all primary gastrointestinal lymphomas and are mostly associated with coeliac disease. They usually express the CD3‐associated T‐cell receptor α/β heterodimer and HML1, and some are related with Epstein–Barr virus (EBV). As far as we know, the present report describes the first case of primary gamma‐delta (γδ) EBV‐associated intestinal T‐cell lymphoma without enteropathy. Only hepatosplenic, nasal and cutaneous γδ T‐cell lymphomas have previously been described.

Methods and results:

Our case concerned a 43‐year‐old man with no history of coeliac disease, who presented with multifocal small bowel involvement showing high grade T‐cell lymphoma with medium sized and large pleomorphic cells and a small pleomorphic T‐cell component. Angioinvasion and angiocentricity were occasionally present. Immunohistochemical studies of lymphoma cells showed a T‐cell γδ phenotype (CD3+, CD2+, TCRδ1+, Vδ2+ and βF1–) without expression of CD4, CD8, CD5, or HML1. Most tumour cells were positive for the cytotoxic granular proteins TiA1 and granzyme B. Rearrangement of the TCRγ chain gene was demonstrated by polymerase chain reaction and in‐situ hybridization with EBER probes revealed strong nuclear positivity in virtually all neoplastic cells.

Conclusion:

We described the first case of primary intestinal γδ T‐cell lymphoma without enteropathy in which EBV might fulfil a pathogenic role.
Metallothionein expression in carcinoma of the gallbladder
Authors: Shukla V K , Aryya N C , Pitale A , Pandey M , Dixit V K , Reddy C D , Gautam A
Published: March 2003

Aims

Metallothioneins (MT) are sulphur‐rich, low molecular‐weight, intracellular metal‐binding proteins with a possible role in carcinogenesis of some human tumours. Metallothionein expression in gallbladder cancer has not been studied previously.

Methods and results

Immunohistochemical expression of metallothionein was studied in 42 gallbladders (27 cases of carcinoma of the gallbladder, eight chronic cholecystitis and seven cases of normal gallbladder). Metallothionein expression was significantly higher in cases with carcinoma of the gallbladder (70.37%) as compared to chronic cholecystitis (25%) and normal gallbladders (0%). There was a trend suggestive of increasing MT expression with increasing histological dedifferentiation of carcinoma of the gallbladder.

Conclusions

The increased expression of MT in cases of carcinoma of the gallbladder may represent an increased exposure to heavy metals, which are known carcinogens, and may have a role in gallbladder carcinogenesis. Metallothionein over‐expression in carcinoma of the gallbladder may be relevant to the poor prognosis and chemoresistance seen in these cases.
Post‐mortem examination after cardiac surgery
Authors: Lee A H S , Gallagher P J
Published: March 2003

Following a recent enquiry into surgery at a paediatric cardiac centre in England, there will be substantial changes in the way that the success and failure of surgical procedures will be monitored and investigated. Post‐mortem examinations on patients dying after cardiac surgery are likely to be performed and reported in more detail. This review describes the protocol that we have developed and summarizes recent clinical and pathological studies that have increased our understanding of postoperative pathophysiology. Close attention should be paid to the history, particularly the operation note. Cardiac failure is the commonest cause of death. We believe this is a clinicopathological diagnosis and provide definitions of preoperative and perioperative cardiac failure. Haemorrhage, stroke, pulmonary emboli and infection are other important causes of death. Methods of dissection are suggested for bypass grafts and valve replacements. Two recent studies show that the post‐mortem examination provides answers to most clinical questions and reveals an unexpected cause of death in 10–15% of patients. There are limitations however: an incomplete or indeterminate cause of death is found in 14–25% of patients, most commonly sudden clinically unexplained death or clinically unexplained cardiac failure soon after surgery.
High metallothionein expression is associated with features predictive of aggressive behaviour in endometrial carcinoma
Authors: McCluggage  , Maxwell  , Hamilton  , Jasani
Published: March 2003

Aims

Metallothioneins (MTs) are a group of ubiquitous low molecular weight proteins with a high affinity for heavy metal ions. The aim of the present study was to investigate MT expression in a series of endometrial carcinomas. We wished to determine whether MT expression in endometrial carcinoma was related to established prognostic factors such as tumour grade, stage and histological type. We also wanted to establish if high MT expression in curettings of endometrial carcinoma was predictive of high expression in the subsequent hysterectomy specimen.

Methods and results

Sixty‐three cases of endometrial carcinoma were included in the study. These comprised 57 endometrioid adenocarcinomas (15 grade 1, 25 grade 2, 17 grade 3), three papillary serous adenocarcinomas, two mucinous adenocarcinomas and one clear cell adenocarcinoma. Forty‐five tumours were stage I, 10 were stage II and eight were stage III. In 28 cases, diagnostic endometrial curettings, performed prior to hysterectomy, were available for study. Immunohistochemical staining was performed using the anti‐MT monoclonal antibody E9. The intensity and distribution of MT staining were assessed using a semiquantitative method. This resulted in an intensity distribution (ID) score out of a maximum of 300. The mean ID score of grade 1 and 2 endometrioid adenocarcinomas was 67 and 63, respectively, while for grade 3 tumours the mean ID score was 114. This was statistically significant (P = 0.05). The three papillary serous adenocarcinomas had high ID scores with a mean of 208. The mean ID score of stage I tumours was 69. This was lower than those of stage II and III tumours which had mean ID scores of 116 and 128, respectively. However, these differences were not statistically significant (P = 0.288). A significant correlation was observed between MT ID scores in endometrial curettings and in the subsequent hysterectomy (P = 0.013).

Conclusions

MT isoforms can be demonstrated in most endometrial adenocarcinomas. High MT ID scores are associated with high grade and high stage endometrial adenocarcinomas and with the aggressive papillary serous adenocarcinoma. Whether this is of value as an independent prognostic factor has yet to be established.
Errors in histopathology reporting: detection and avoidance
Authors: Ramsay A D
Published: March 2003

The histopathological diagnosis is the bedrock of modern oncology, and plays a major role in the treatment of many other types of disease. Errors in these reports can critically affect patient care and may become the subject of media concern. This article considers how audit in histopathology can provide information about errors and inconsistencies in the diagnosis of surgical specimens. The use of audit to generate information about the background level of errors in pathology reports is reviewed, along with findings about the nature of these errors and the types of specimens more commonly affected. Generic audit strategies that can be used to minimize the risk of errors in reports are discussed, together with the use of audit to evaluate diagnostic criteria and pathological scoring or grading systems. The role of audit in determining the informational content of reports is included, and there is consideration of the relationship between sample size and error rates. The limited extent to which audit can be used to assess the performance of individual pathologists is also covered.
Predicting the future: a critical appraisal of cancer prognosis studies
Authors: Hall  , Going
Published: March 2003

Many studies have attempted to define useful prognostic and predictive factors in cancer but few have achieved acceptance in clinical practice because of methodological weaknesses. These include failure to test clearly formulated hypotheses, inadequate sample size, inappropriate multiple significance testing, arbitrary definition of patient groups, inadequately reproducible assays, and failure to verify prognostic factors with data independent of the data which suggested the original hypothesis. This unsatisfactory situation will persist until critical attention is routinely paid to study design and prospective validation of supposed prognostic and predictive factors, without which classical approaches will be suboptimally exploited and the flood of data from new molecular technologies will not be used effectively. We propose that prognostic factors should be evaluated in three phases: I, assay definition; II, retrospective testing; III, prospective testing, ideally as a designed part of clinical trials.
Hepatosplenic γδ T‐cell lymphoma: relation to Epstein–Barr virus and activated cytotoxic molecules
Authors: Ohshima  , Haraoka  , Harada  , Kamimura  , Suzumiya  , Kanda  , Kawasaki  , Sugihara  , Kikuchi
Published: March 2003

Aims

Hepatosplenic γδ T‐cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenia. Epstein–Barr virus (EBV) infection and activated cytotoxic molecules (granzyme and perforin) are uncommon in hepatosplenic γδ CTL. EBV infection and activated cytotoxic molecules are occasionally detected in non‐hepatosplenic γδ TCL. We describe the clinicopathological features of three Japanese cases who were not immunodeficient.

Methods and results

All cases showed γδ T‐cell type (CD2+, CD3+, T‐cell receptor (TCR)δ‐1+, βF1−). Two cases expressed natural killer (NK) cell‐associated antigens (CD8–, CD16+, CD56+; CD8−, CD16−, CD56+), and one expressed CD8 (CD8+, CD16−, CD56−). All cases expressed cytotoxicity‐associated molecules (perforin, granzyme B, TIA‐1 and Fas ligand). However, perforin and Fas ligand were not detected in one case. In‐situ hybridization analysis with EBER probes revealed strong nuclear positivity in all neoplastic cells. In addition, two cases showed clonal bands of the EBV terminal repeat (TR) gene. Cytologically, instead of the presence of monomorphic medium‐sized cells, our three cases showed pleomorphic medium‐sized and large cells.

Conclusions

Our γδ TCL cases were clinicopathologically considered to be compatible with hepatosplenic γδ T‐cell lymphoma. However, with regard to EBV association, activated cytotoxic profile and cytological features they resembled non‐hepatosplenic γδ TCL. EBV may play a role in this disease by inducing cellular activation.
Overexpression of 27‐kDa heat shock protein relates to poor histological differentiation in human oesophageal squamous cell carcinoma
Authors: Lambot  , Peny  , Fayt  , Haot  , Noël
Published: March 2003

Aims

Various stress conditions such as heat, chemical and mechanical stresses are known to play a major role in oesophageal squamous cell carcinoma development. Our goal was to evaluate whether changes in stress‐induced 27‐kDa heat shock protein (HSP27) expression could be demonstrated during oesophageal carcinogenesis.

Methods and results

HSP27 expression was studied using immunohistochemistry on formalin‐fixed, paraffin‐embedded tissue sections from 21 oesophageal squamous cell carcinomas occurring in smokers and/or alcohol abusers. Oesophagus from healthy patients (controls) (five), chemical (eight) and infectious oesophagitis (six) were also included in the study. In normal oesophagus, the protein is present only in the upper epithelial layers. In contrast, in chemical or infectious oesophagitis its expression is strong and occurs in all the epithelial layers including the basal layer. In non‐tumoral oesophageal mucosa from smoking and/or drinking patients adjacent to invasive carcinoma, the distribution of the protein is patchy and irregular. In malignant areas, HSP27 protein expression increases drastically from dysplastic lesions to invasive carcinoma, being highest in the less differentiated areas.

Conclusions

In human oesophagus, HSP27 expression is induced by various stresses but alcohol and tobacco generate focal perturbations in the stress response. Tumour immunoreactivity for this protein increases with the anaplasia of the tumour, as in some other tumours in which it is considered to play a role in drug resistance. To our knowledge, these data have not been previously described for oesophageal squamous cell carcinoma.
Expression of steroid hormone receptors, their regulated proteins, and bcl‐2 protein in myofibroblastoma of the breast
Authors: Magro G , Bisceglia M , Michal M
Published: March 2003

Aims

To investigate the possible role of steroid hormones in the pathogenesis of myofibroblastoma (MFB) of the breast, we analysed the immunohistochemical expression of oestrogen, progesterone, androgen receptors, their regulated proteins and bcl‐2 protein in a series of this rare tumour.

Methods and results

Paraffin‐embedded sections from seven cases of MFB of the breast (five male; two female) were immunohistochemically tested for the expression of oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), oestrogen‐regulated pS2 protein, androgen‐regulated prostate‐specific antigen (PSA) and bcl‐2 protein. Rare cases of benign spindle cell tumours or tumour‐like lesions of the breast (primitive fibromatosis, inflammatory pseudotumour, muscular hamartoma) which enter into the differential diagnosis with MFB, were also investigated and compared with MFB. All cases of MFB showed a diffuse (70–90% of neoplastic cells) and strong nuclear labelling with ER and PR, whereas AR was expressed only in three cases (two men and one woman) in about 60–70% of cells. Conversely, no immunostaining was detected for the pS2 protein and PSA. bcl‐2 protein immunoreactivity was found in all cases of MFB, although with a variable degree of expression. No expression for steroid hormone receptors, their regulated‐proteins and bcl‐2 protein was observed in the rare benign spindle cell lesions of the breast included in this study.

Conclusion

The in‐situ detection of ER, PR and AR suggests that steroid hormones and their receptors are implicated in the pathogenesis of breast MFB. The consistent demonstration of bcl‐2 protein, associated with a positive ER/PR status, provides evidence that bcl‐2 may be an oestrogen‐regulated protein also in MFB and that probably plays a role in the tumorigenesis. Finally, we postulate that the ER/PR and bcl‐2 positive immunoprofile of MFB of the breast, in contrast to the negative profile of other rare primitive benign spindle cell lesions of the breast herein studied, might be exploited as an ancillary diagnostic aid in differential diagnosis of doubtful cases.
CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but not prognosis
Authors: Sneath R J , Mangham D C
Published: March 2003

Aims

: We immunohistochemically determined the expression of CD44 standard and splice variant isoforms in a series of synovial sarcomas and sought correlations with histological subtype and clinical parameters including outcome.

Methods  and results:

From 39 patients, a total of 56 formalin‐fixed and paraffin‐embedded tumour samples (including initial, recurrent and metastatic tumours) were used to immunohistochemically evaluate the expression of epitopes encoded by CD44s and the CD44 splice variants CD44v3–v10. Significance of proposed prognostic indicators was evaluated in relation to the survival, time to local recurrence and time to metastases using log‐rank analysis. Sixty‐four percent of synovial sarcomas expressed CD44s and 46% expressed CD44v3–v10 (var). Synovial sarcomas with epithelial or epithelioid areas preferentially expressed CD44s in these areas when compared with the spindle cell element. There were no correlations with clinical parameters or outcome.

Conclusions: 

The expression of CD44 was not found to correlate with survival, local recurrence or metastatic ability. In synovial sarcoma, CD44 and variant isoform expression appears to be associated with the degree of epithelial differentiation. CD44 expression in synovial sarcoma shows interesting similarities to CD44 expression in embryological epitheliogenesis.