bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic differentiation of a European caddisfly: past and present gene flow among fragmented larval habitats
Authors: Wilcock Helen R. , Hildrew Alan G. , Nichols Richard A.
Published: March 2003

We describe the genetic structure of a freshwater insect species and interpret it in terms of present‐day population dynamics and possible postglacial colonization history. The sampling regime represented a large area of the species range in northwest Europe, particularly focusing on Britain, a region relatively neglected in molecular population genetic studies. Plectrocnemia conspersa generally showed low levels of genetic variation across the sampled populations (Nei’s D = 0.0138) and subdivision was unrelated to the pattern of the drainage network. However, the results do suggest that populations across the region are not at equilibrium and that British populations still show effects of the recolonization of the species following the last glacial maximum. Levels of genetic diversity were lower in Britain than in mainland Europe. Two‐dimensional scaling showed genetic differentiation between major regions and the pattern of genetic diversity indicates a more recent origin of populations in the north and west of the area compared with the south and east. We argue that, despite the highly fragmented larval habitat, dispersal over tens of kilometres is frequent. Over longer distances, however, P. conspersa does still show evidence of founder effects and postglacial range expansion into Britain.
Frequent cytoplasmic exchanges between oak species that are not closely related: Quercus suber and Q. ilex in Morocco
Authors: Belahbib N. , Pemonge M.‐H. , Ouassou A. , Sbay H. , Kremer A. , Petit R. J.
Published: March 2003

Chloroplast (cp) and mitochondrial (mt) DNA variation were studied in 97 populations of cork oak (Quercus suber) in Morocco; in 31 of these populations, holm oak (Quercus ilex), a clearly distinct species, also occurred and was compared with Q. suber. Three cpDNA and one mtDNA primer pairs were used in the survey, each in combination with one restriction enzyme. Six haplotypes belonging to two very divergent lineages were detected; one lineage predominates in each species, and is probably ancestral, as inferred from comparisons with other oak species. In the mixed‐species populations, cytoplasmic genomes were frequently shared across species, as indicated by an introgression ratio of 0.63. This index is a new measure of the propensity of species to share locally genetic markers, varying from zero (complete differentiation) to one (no differentiation). By contrast, more closely related deciduous oak species (Q. robur, Q. petraea and Q. pubescens) have introgression ratios varying from 0.82 to 0.97. The introgression events appear to have been more frequent in the direction Q. ilex (female) × Q. suber (male), a finding which seems attributable to the flowering phenology of these two species. This asymmetry may have favoured immigration of Q. suber beyond its main range, in regions already colonized by Q. ilex. There, rare hybridization and further introgression through long distance pollen flow have established populations that are morphologically indistinguishable from Q. suber but that have cytoplasmic genomes originating from the local Q. ilex populations.
Multiple causation of phylogeographical pattern as revealed by nested clade analysis of the bamboo viper (Trimeresurus stejnegeri) within Taiwan
Authors: Creer S. , Malhotra A. , Thorpe R. S. , Chou W.‐H.
Published: March 2003

In order to assess the utility of nested clade analysis, both standard phylogenetic algorithms and nested clade analysis were performed on a geographically widespread survey of mitochondrial DNA haplotypes of the bamboo viper, Trimeresurus stejnegeri, within Taiwan. Gross tree topologies were congruent for all analyses and indicated the presence of two geographically overlapping clades within Taiwan. The smaller lineage was restricted to the north and east coasts, whereas the larger lineage occupied all but the northern range of the species within Taiwan including the Pacific offshore populations of Green and Orchid Islands. The phylogeographical pattern supports the existence of at least one colonization event from the continent since the initial isolation of Taiwan from the mainland in the Pliocene. However, determining the exact number of colonization events was not possible due to the simultaneous vicariant forces of hypothesized continental landbridge connections and the occurrence of dramatic in situ orogenesis throughout the Pleistocene. Nested clade analysis provided multiple temporal and spatial population historical inferences that are not possible with standard analyses and therefore should become widely applied to future phylogeographical studies.
Prevailing triple infection withWolbachiainCallosobruchus chinensis(Coleoptera: Bruchidae)
Authors: Kondo Natsuko , Ijichi Nobuyuki , Shimada Masakazu , Fukatsu Takema
Published: March 2003

Prevailing triple infection with three distinctWolbachiastrains was identified in Japanese populations of the adzuki bean beetle,Callosobruchus chinensis. When a polymerase chain reaction (PCR) assay was conducted using universal primers forftsZandwsp,Wolbachiawas detected in all the individuals examined, 288 males and 334 females from nine Japanese populations. PCR–restriction fragment length polymorphism (RFLP) analysis of clonedwspgene fragments from single insects revealed that three types ofwspsequences coexist in the insects. Molecular phylogenetic analysis of thewspsequences unequivocally demonstrated thatC. chinensisharbours three phylogenetically distinctWolbachia, tentatively designated as wBruCon, wBruOri and wBruAus, respectively. Diagnostic PCR analysis using specific primers demonstrated that, of 175 males and 235 females from nine local populations, infection frequencies with wBruCon, wBruOri and wBruAus were 100%, 96.3% and 97.0%, respectively. As for the infection status of individuals, triple infection (93.7%) dominated over double infection (6.1%) and single infection (0.2%). The amounts of wBruCon, wBruOri and wBruAus in field‐collected adult insects were analysed by using a quantitative PCR technique in terms ofwspgene copies per individual insect. Irrespective of original populations, wBruCon and wBruOri (107–108wspcopies/insect) were consistently greater in amount than wBruAus (106–107wspcopies/insect), suggesting that the population sizes of the threeWolbachiastrains are controlled, although the mechanism is unknown. Mating experiments suggested that the threeWolbachiacause cytoplasmic incompatibility at different levels of intensity.
Is digestive capacity limiting growth at low temperatures in roach?
Authors: Hardewig I. , Van Dijk P. L. M.
Published: March 2003

In roach Rutilus rutilus growth ceases below a temperature threshold of 12° C. This cessation of growth is accompanied by a reduction in feeding. Do roach decrease feeding in the cold because of reduced energy demand, caused by the decelerating effect of low temperature on metabolism and growth, or is feeding directly limited by low temperatures, leading to reduced growth rates? It was found that at low temperatures the intake and digestion of food may be limited by reduced activities of digestive enzymes. Trypsin, amylase and γ‐glutamyl transferase showed a negative compensation with respect to temperature, resulting in very low activities at acclimation temperatures of ≤12° C. Trypsin activity, falling from 400·5 ± 131·2 U g−1 fresh mass of the gut at 27° C to 12·5 U g−1 fresh mass at 4° C, displayed the strongest linear correlation with growth rates, suggesting that trypsin activities may set a limit to growth in the low temperature range. If protein digestion is limiting at low temperatures, this should be reflected in reduced concentrations of amino acid in the white muscle. The size of the total amino acid pool was not affected by temperature acclimation and ranged between 19·2 ± 6·2 and 25·2 ± 3·6 µmol g−1 fresh mass of the white muscle. A decrease, however, was found of several amino acids, mainly of threonine and glutamine, in the low temperature range. Low concentrations of the essential amino acid threonine (0·14 ± 0·03 µmol g−1 fresh mass at 12° C and 0·12 ± 0·05 µmol g−1 fresh mass at 4° C) were probably due to nutritional or digestional limitations and may therefore have resulted from reduced trypsin activity in the cold. The non‐essential amino acid glutamine, however, can be endogenously synthesized and its low level observed at 4° C (0·16 ± 0·09 µmol g−1 fresh mass) was not necessarily a result of low trypsin activities. It is more likely that low temperatures impair glutamine synthesis. The possibility that glutamine concentrations may be down regulated under conditions when anabolic processes are not advantageous is discussed.
The reproductive biology of the crystal goby with a comparison to that of the transparent goby
Authors: Caputo V. , Mesa M. L. , Candi G. , Cerioni P. N.
Published: March 2003

A histological analysis of the gonad of the pelagic crystal goby Crystallogobius linearis, from the coastal central area of the Adriatic Sea, showed it to be a truly semelparous species; after the first spawning the mature gonads of both males and females appeared to have lost the capability for further spawning. Mature females had very low fecundity (200–700 mature oocytes) and small egg size (0·2–0·55 mm) similarly to other progenetic species. This reproductive strategy is compared with that of Aphia minuta, and a possible cause for the post‐reproductive mortality of the two gobies is suggested and discussed.
Benign mucinous cystadenoma with stromal luteinization during pregnancy: A hormonally responsive tumor and a rare cause of fetal intrauterine growth restriction
Authors: Qublan Hussein S. , Al‐Ghoweri Ahmad S. , Al‐Kaisi Nabih S. , Abu‐khait Sami A.
Published: March 2003

A 32‐year‐old woman, gravida 4, para 3, had a benign right ovarian mucinous cystadenoma. It was diagnosed 1 month before conception, measured 9 × 7 cm, and reached 33 × 24 × 20 cm at 38 weeks gestation. Cesarean delivery of a 2250 g normal female infant took place, and the removal of a 6300 g right ovarian cystic mass was also performed. Microscopic and immunohistochemical studies of the cyst wall revealed stromal luteinization and a strong reaction with antiserum to testosterone, estrogen and progesterone.
Relationship between endometrial estrogen and progesterone receptors, and sonographic endometrial appearance in the preovulatory phase
Authors: Kim Chung‐hoon , Chae Hee‐Dong , Huh Jooryung , Kang Byung‐Moon , Chang Yoon Seok , Nam Joo‐Hyun
Published: March 2003

Objectives:
 The purpose of the present study is to evaluate the relationship between endometrial concentrations of estrogen receptor (ER) and progesterone receptor (PR), and sonographic endometrial findings in the preovulatory phase of menstrual cycle.

Study Design:
 In 45 cycles of 45 infertile women with tubal factor only, transvaginal sonographic assessments and biopsy for immunohistochemical staining of the endometrium were made in the preovulatory phase of unstimulated, normal menstrual cycle. Immunohistochemical localization of ER and PR was scored according to intensity of staining and proportion of cells specifically stained in glandular epithelium and stroma, and the results were analyzed according to the sonographic endometrial thickness (<6 mm, 6–10 mm, or >10 mm) and pattern. Endometrial patterns were classified as A, centrally hyperechogenic triple‐line pattem or non‐A, not triple‐line.

Results:
 There were no significant differences in the endometrial thickness, serum estradiol level and serum progesterone level between A and non‐A groups. The receptor scores of epithelial and stromal ER and epithelial PR were comparable in A and non‐A groups. However, the receptor score of stromal PR was significantly higher in A group, with 4.8 ± 1.4 compared with 2.7 ± 1.7 in non‐A group (P < 0.001). There were no differences in the receptor scores of epithelial ER, epithelial PR, stromal ER and stromal PR among the 3 groups according to the endometrial thickness.

Conclusions:
 This study suggests that high PR expression in endometrial stroma could be related to the sonographic triple‐line or multilayered pattern of endometrium in the preovulatory period.
Absconding of patients from an independent UK psychiatric hospital: a 3‐year retrospective analysis of events and characteristics of absconders
Authors: Dickens G. L. , Campbell J.
Published: March 2003

The need for accurate local information on the scale, nature and outcome of absconding or Absence Without Leave (AWOL) from an independent UK psychiatric hospital led to this 3‐year (1997–1999) retrospective analysis of of AWOL data. One hundred and forty‐eight AWOL incidents involving 88 patients were identified. Absconders were found to be significantly younger, more likely to be detained upon admission and more likely to be unmarried than a control group (n = 1378) of non‐absconders. There were no significant differences for sex, length of admission or ethnicity. Descriptive data on the circumstances surrounding AWOL events are given, with at least 24 (16.2%) incidents having serious adverse outcomes. Baseline absconding rates are presented for the specialist clinical divisions within the hospital. There is a need for more detailed studies of absconding by patients within the Adolescent Mental Health Service subgroup where the absconding rate was relatively high and engagement in risk activity whilst AWOL relatively frequent.
P‐glycoprotein expression by cancer cells affects cell cytotoxicity and cell‐cycle perturbations induced by six chemotherapeutic drugs
Authors: Galmarini Carlos M.
Published: March 2003

Background: P‐glycoprotein (P‐gp)–mediated chemoresistance plays an important role in drug resistance.

Methods: We investigated if P‐gp expression by cancer cells affects cell cytotoxicity and cell‐cycle perturbations induced by six commonly used chemotherapeutic agents (doxorubicin, daunorubicin, mitoxantrone, vinblastine, paclitaxel, and colchicine). For this purpose, we used KB cell lines as a model and flow cytometric cell viability and drug‐induced cell‐cycle perturbation–based methods. We continuously cultured KB cell lines, in the presence of various anticancer agents and measured the cell‐cycle kinetics and percentage of cell viability by flow cytometry at different time intervals.

Results: The highly resistant cell line KB V‐1 was significantly less susceptible to drug cytotoxicity than the sensitive cell line KB 3‐1. KB V‐1 cells cultured with different chemotherapy agents continued cell‐cycle progression without any significant perturbation of cell compartment distribution. Addition of verapamil, by inhibiting P‐gp, reversed resistance thereby increasing drug cytotoxicity and allowing the appearance of drug induced cell‐cycle perturbations.

Conclusions: We conclude that P‐gp interferes with cell cytotoxicity and cell‐cycle perturbations induced by anticancer agents. Flow cytometry can be used to conveniently detect P‐gp–mediated chemoresistance by cancer cells as it allows the analysis of cell cytotoxicity and cell‐cycle modifications after exposure to specific chemotherapeutic and reversal agents.
Views and Experiences of People with Intellectual Disabilities and Their Families. (2) The Family Perspective
Authors: Grant Gordon , Ramcharan Paul
Published: March 2003

The aim of the present paper is to distil findings from research into the views and experiences of families of people with intellectual disabilities (IDs). It draws from the authors' report on the views and experiences of users and carers, theDoH Research Initiative on Learning Disability: Proposal for a Research Review on the Views and Experiences of Users and Carers, which was commissioned by the Department of Health, and was intended to inform some of the thinking behindValuing Peopleand the associated research programme. The present paper traces the development and scope of research on family carers in relation to the personal and psychological experience of care as well as in relation to receipt of services. Theoretical and methodological gaps in the literature are outlined. Social systems theory is proposed as a means of addressing the requirements of a future research agenda about family care.
Unravelling R gene‐mediated disease resistance pathways in Arabidopsis
Authors: Parker Jane E. , Feys Bart J. , Van Der Biezen Erik A. , Noël Laurent , Aarts Nicole , Austin Mark J. , Botella Miguel A. , Frost Louise N. , Daniels Michael J. , Jones Jonathan D. G.
Published: March 2003

Molecular genetic approaches were adopted in the model crucifer, Arabidopsis thaliana, to unravel components of RPP5‐ and RPP1‐mediated disease resistance to the oomycete pathogen, Peronospora parasitica. The products of RPP5 and three genes comprising the RPP1 complex locus belong to a major subclass of nucleotide‐binding/leucine‐rich repeat (NB‐LRR) resistance (R) protein that has amino‐terminal homology to the cytoplasmic domains of Drosophila and mammalian Toll and interleukin‐1 family receptors (the so called ‘TIR’ domain). Similarities in the domain architecture of these proteins and animal regulators of programmed cell death have also been observed. Mutational screens revealed a number of genes that are required for RPP5‐conditioned resistance. Among these are EDS1 and PAD4. Both EDS1 and PAD4 precede the function of salicylic acid‐mediated plant responses. The EDS1 and PAD4 genes were cloned and found to encode proteins with similarity to the catalytic site of eukaryotic lipases, suggesting that they may function by hydrolysing a lipid‐based substrate.
Brome mosaic virus, good for an RNA virologist’s basic needs
Authors: Kao C. Cheng , Sivakumaran K.
Published: March 2003

Taxonomic relationship: Type member of the Bromovirus genus, family Bromoviridae. A member of the alphavirus‐like supergroup of positive‐sense single‐stranded RNA viruses.

Physical properties: Virions are nonenveloped icosahedrals made up of 180 coat protein subunits (
Fig. 1). The particles are 26 nm in diameter and contain 22% nucleic acid and 78% protein. The BMV genome is composed of three positive‐sense, capped RNAs: RNA1 (3.2 kb), RNA2 (2.9 kb), RNA3 (2.1 kb) (
Fig. 2).

Electron micrograph of brome mosaic virus. The average diameter of each particle is 26 nm.

image

Schematic of BMV RNAs, and the initiation sites for viral RNA synthesis. (A) The RNAs are capped with a 7‐methyl‐guanylate at the 5′ end and possess a tRNA‐like structure at the 3′ end. The initiation sites of minus‐strand RNA synthesis from the penultimate cytidylate are indicated with an arrow. The protein coding sequences are indicated in boxes. The position of the domain in protein 1a that is highly conserved in capping‐associated proteins is denoted with verticle stripes. The region denoted with horizontal stripes contains helicase‐like motifs. The grey region in 2a contains the central RdRp‐like sequences. (B) Minus‐strand RNA3 is used to promote synthesis of genomic RNA3 and subgenomic RNA4 (orf, open reading frame).

image

Viral proteins: RNA1 encodes protein 1a, containing capping and putative RNA helicase activities. RNA2 encodes protein 2a, a putative RNA‐dependent RNA polymerase. RNA3 codes for two proteins: 3a, which is required for cell‐to‐cell movement, and the capsid protein. The capsid is translated from a subgenomic RNA, RNA4 (1.2 kb).

Hosts: Monocots in the Poacea family, including Bromus inermis, Zea mays and Hordeum vulgare, in which BMV causes brown streaks. BMV can also infect the dicots Nicotiana benthamiana and several Chenopodium species. In N. benthamiana, the infection is asymptomatic while infection of Chenopodium can cause either necrotic or chlorotic lesions.

Useful website:
http://www4.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/10030001.htm
In situ PCR detection of phytoplasma DNA in embryos from coconut palms with lethal yellowing disease
Authors: Cordova Ivan , Jones Phil , Harrison Nigel A. , Oropeza Carlos
Published: March 2003

DNA of the lethal yellowing (LY) phytoplasma was detected in 13 of 72 embryos from fruits of four diseased Atlantic tall coconut palms by polymerase chain reaction (PCR) assays employing phytoplasma universal rRNA primer pair P1/P7, nested LY group‐specific rRNA primer pair 503f/LY16Sr or LY phytoplasma‐specific nonribosomal primer pair LYF1/R1. Phytoplasma distribution in sectioned tissues from six PCR positive embryos was determined by in situ PCR and digoxigenin‐11‐deoxy‐UTP (Dig) labelling of amplification products. Dig‐labeled DNA products detected by colourimetric assay were clearly evident on sections from the same three embryos investigated in detail by in situ PCRs employing primer pairs P1/P7 or LYF1/R1. Deposition of blue–green stain on sections as a result of each assay was restricted to areas of the embryos corresponding to the plumule and cells ensheathing it. By comparison, similarly treated embryo sections derived from fruits of a symptomless Atlantic tall coconut palm were consistently devoid of any stain. Presence of phytoplasma DNA in embryo tissues suggests the possible potential for seed transmission which remains to be demonstrated.
Characterization of homologues of the apple proliferation immunodominant membrane protein gene from three related phytoplasmas
Authors: Morton Anne , Davies David L. , Blomquist Cheryl L. , Barbara Derek J.
Published: March 2003

Homologues of the immunodominant membrane protein gene from apple proliferation (AP) phytoplasma have been cloned and sequenced for three further members of the AP subclade, namely European stone fruit yellows, peach yellow leaf roll and a European isolate of pear decline (PD). The putative translation products of all three were similar in size to that of AP and all had a transmembrane region towards the N‐terminus and a large C‐terminal hydrophilic domain, probably held on the outside of the cell membrane in vivo. Sequence similarities for the putative proteins were compared with interrelationships of the phytoplasmas as measured by rRNA gene sequence similarity. The proteins from AP and PD were more similar (57% identical in the major hydrophilic domain) than those for any other pair (31–34%), but these two phytoplasmas were not more closely related by rRNA gene sequences than other pairs. The possibility that the relative similarities of these proteins is related to the host is discussed. It is suggested that the similarity of the AP and PD proteins may reflect the fact that these two proteins have narrow plant host ranges in two closely related genera in the tribe Maloideae (family Rosaceae), whilst the other two have broader host ranges, mainly in the tribe Prunoideae.
‘Healthline’: a new service from the College of Health
Authors: RIGGE MARIANNE
Published: March 2003

One of the crucial roles of the College of Health is to disseminate health education and information to the public. An investigation into Tel‐Med, a US service through which some 350 tapes on a variety of health and medical topics are instantly available via the ordinary telephone service, is described. The experience of the College of Health in launching a similar service in Britain called Healthline is reported and discussed.
Biomedical libraries and information services in Great Britain*
Authors: TABOR R. B.
Published: March 2003

An overview of the development and current state of biomedical library and information service provision in Great Britain is given. Emphasis is laid on the role of National Health Service (NHS) Regional Library Systems in England and Wales and current trends in the Wessex Regional Library and Information Service (WRLIS) are described.
Responding to the reforms—are we meeting the need?
Authors: RODDHAM MIKE
Published: March 2003

Changes in postgraduate medical education funding have had a major impact on the management of NHS library services. This paper looks at the nature of these services, by reviewing the literature on the information‐gathering needs and practices of different groups of health‐care professionals, and by relating the findings to the types of information service currently available. It is concluded that library and information professionals need to develop services that are more accurately attuned to the needs of their users, and various ways of approaching this objective are suggested.
Autopsy findings in 27 children with haemophagocytic lymphohistiocytosis
Authors: Öst  , Nilsson‐Ardnor  , Henter
Published: March 2003

Aims:

Primary haemophagocytic lymphohistiocytosis (HLH) is a fatal childhood disorder. The diagnosis is difficult to establish, clinically as well as histopathologically, and it is markedly underdiagnosed. Because of these difficulties, we wanted to elucidate the histopathological findings in population‐based patient material.

Methods and results:

The post‐mortem findings in 27 children with primary HLH diagnosed in Sweden between 1971 and 1986 was reviewed. Twelve of these patients had an affected sibling and three additional children had parental consanguinity. Some of the children showed generalized disease, whereas in others only one or a few organs were affected. The major histological alteration was an accumulation of primarily lymphocytes, but also of histiocytes, some of which exhibited evidence of haemophagocytosis. The haemophagocytic activity may be difficult to detect if there are pronounced post‐mortem changes, particularly in the spleen, and it is therefore preferable to perform the autopsy as soon as possible after death in order to minimize autolysis. Haemophagocytosis was most commonly observed in the spleen (17/24), the lymph nodes (17/23) and the bone marrow (9/23), indicating that a negative bone marrow examination does not rule out this diagnosis. Three additional patients had discrete signs of haemophagocytosis in the bone marrow. In the spleen, the lymph nodes and the bone marrow, lymphocytic depletion, pronounced in some cases, could be observed, even without prior treatment with steroids or cytostatics. In the liver, most of the patients demonstrated an infiltration of lymphocytes into the portal tracts similar to that seen in chronic persistent hepatitis (22/27), a finding which is uncommon in infancy and therefore suggestive of the diagnosis HLH. Other organs involved included the thymus, lungs, intestine, pancreas, kidney, heart and striated muscle.

Conclusions:

The diagnosis of HLH must be based on clinical, histological and additional laboratory findings. A negative bone marrow examination is common. Previous treatment with steroids and/or cytostatic drugs may attenuate or even eliminate the typical histological findings. Liver findings similar to those in chronic persistent hepatitis are common.
CD44 variant expression in inflammatory colonic mucosa is not disease specific but associated with increased crypt cell proliferation
Authors: Fromont Hankard  , Cezard  , Aigrain  , Navarro  , Peuchmaur
Published: March 2003

Aims:

A recent study reported increased epithelial expression of CD44 variants in ulcerative colitis (UC) compared with Crohn's disease (CD). However, the use of CD44 expression for diagnostic purposes in inflammatory bowel disease has been controversial, and the meaning of the appearance of CD44 variants in epithelial colonic cells remains unknown. We investigated the relationship between CD44 isoform expression and crypt cell proliferation in paediatric colitis.

Methods and results:

The expression of CD44v3, CD44v6, and MIB1 (proliferation marker) was studied by immunohistochemistry on surgical colonic samples of UC (n = 13), CD (n = 10), colostomy resections with non‐specific mucosal inflammation (NSMI) (n = 3), and normal controls (n = 5). The proliferation index (% of MIB1 positive cells) was assessed in both v6 positive and v6 negative crypts. Epithelial expression of CD44v3 and v6, negative in normal controls, was variable and focal in colitis. No preferential expression of CD44 variants was found in UC. The proliferation index was dramatically increased in v6 positive crypts compared with v6 negative crypts in UC, CD and NSMI.

Conclusions:

These data suggest that CD44 variant staining is not a useful marker for distinguishing paediatric UC from CD, and that CD44v6 expression in the inflamed colonic mucosa is not disease specific but is related to crypt cell proliferation.
Clear cell carcinoma of the pancreas: an adenocarcinoma with ductal phenotype
Authors: Lüttges  , Vogel  , Menke  , Henne‐Bruns  , Kremer  , Klöppel
Published: March 2003

Aims

Primary clear cell carcinoma of the pancreas resembling metastatic renal carcinoma has only rarely been described. To date it has been poorly characterized as a distinct tumour entity.

Methods and results

We report a case of clear cell carcinoma in a 53‐year‐old man involving the head of the pancreas and which had a small intraductal papillary component. The clear cell portion comprised about 90% of the tumour mass. It showed predominantly a solid growth pattern with a few scattered tubular structures. Immunocytochemically the tumour cells stained positively for cytokeratins 7, 8, 18 and 19, whereas the reaction for vimentin and neuroendocrine markers was negative. K‐ras analysis revealed a point mutation at codon 12 with mutation of GGT to GAT.

Conclusion

The intraductal tumour component of this clear cell carcinoma as well as the cytokeratin pattern and the K‐ras mutation suggest that this rare type of pancreatic cancer has a ductal phenotype.
Histological demarcation of lateral borders: an unsupportable criterion for distinguishing malignant melanoma from Spitz naevus and compound naevus
Authors: Okun M R
Published: March 2003

Aims

The objective of this study was to determine the validity of sharpness of lateral margins (an important component of the pattern analysis method) as a criterion for the histological distinction of naevi from malignant melanoma.

Methods and results

The sharpness of lateral borders in a series of histologically unequivocal malignant melanomas, Spitz naevi and compound naevi, chosen at random from dermatopathology slide archives, was determined. The incidence of poor demarcation of lateral borders in malignant melanomas was about equal to that of Spitz naevi and was significantly less than in compound naevi. The sharpness of lateral borders frequently varies with level of sectioning.

Conclusions

The proposal that malignant melanomas have a significantly greater incidence of poor demarcation of lateral borders than benign melanocytic neoplasms (Spitz naevi and compound naevi) was shown to be without validity on cited empirical grounds as well as theoretical grounds (the lack of constancy of pattern from a 3‐dimensional standpoint).
Differentiation of desquamative interstitial pneumonia (DIP) from pulmonary adenocarcinoma by immunocytochemistry
Authors: Mutton A E , Hasleton P S , Curry A , Bishop P W , Egan J , Carroll K B , Hanley S
Published: March 2003

Aim

After a misdiagnosis of pulmonary adenocarcinoma as desquamative interstitial pneumonia (DIP), we investigated whether immunohistochemical markers could differentiate these conditions.

Methods and results

Three cases of DIP and one pulmonary adenocarcinoma masquerading as DIP were studied by light and electron microscopy. All cases were mucin‐negative. The cases of DIP were CD68 positive but cytokeratin‐negative. The adenocarcinoma was cytokeratin‐positive (AE1/3 and CAM5.2), as well as showing some CD68‐positive cells. Markers for carcinoma (CEA, Ber‐EP4, and Leu M1) were negative in all cases. Ultrastructurally the adenocarcinoma appeared to be derived from Type II pneumocytes.

Conclusion

Before a diagnosis of DIP is made, cytokeratin markers should be used.
Gains and losses of CD44 expression during breast carcinogenesis and tumour progression
Authors: Bànkfalvi À , Terpe H‐J , Breukelmann D , Bier B , Rempe D , Pschadka G , Krech R , Böcker W
Published: March 2003

Aims

This study was performed to investigate whether the CD44 immunophenotype of breast lesions correlates with the clinical evolution and prognosis of breast cancer.

Methods and results

One‐hundred and fifty‐two routinely processed normal, benign and malignant breast tissue samples were investigated by the following monoclonal antibodies: CD44 s (F10–44–2), CD44v3 (3G5), CD44v4 (11.10), CD44v5 (VFF‐8), CD44v6 (VFF‐18), CD44v7 (VFF‐9), CD44v9 (11–24) after wet autoclave pretreatment for antigen retrieval. We found that: (1) in normal breast tissues luminal epithelial cells lacked detectable CD44 in contrast to basal cells, which constitutionally expressed CD44 s, v3, v5 v6 and v9 isoforms; (2) in the intraductal compartment of benign hyperplastic lesions, there was scattered or focal staining for CD44 s, v5, v6, v7 and v9 isoforms; (3) in neoplastic lesions restricted neo‐expression of CD44v3 and v4 was detected; and (4) the CD44 immunophenotype of invasive breast carcinomas was influenced largely by differentiation grade, steroid receptor status of the tumours and significantly correlated with metastatic involvement of the axillary lymph nodes.

Conclusions

Qualitative and quantitative changes of CD44 expression are implicated in early stages of breast carcinogenesis. The restricted neo‐expression of certain CD44 isoforms in breast neoplasias suggests that CD44 might be a potential target for future antibody‐based tumour therapy.
Ovarian hepatoid yolk sac tumours: morphological, immunohistochemical and ultrastructural features
Authors: Devouassoux‐Shisheboran  , Schammel  , Tavassoli
Published: March 2003

Aim

The clinicopathological, immunohistochemical and ultrastructural features of two ovarian hepatoid yolk sac tumours (H‐YST) from our files are reviewed.

Methods and results

Using avidin–biotin–peroxidase complex technique, the immunoprofile of these tumours was compared to that of a classic yolk sac tumour and to that previously reported for hepatocellular carcinomas. The clinicopathological and morphological features of our cases are similar to the seven previously reported ovarian cases. This rare germ cell tumour occurs in young females (mean age = 17.6 years) and presents most commonly with abdominal pain and a large ovarian mass (average size = 140 mm). Histologically, the tumours display a striking resemblance to hepatocellular carcinoma. The absence of an associated typical pattern of yolk sac tumour or other germ cell neoplasm may make it difficult to recognize the germ cell origin of this lesion. Our cases demonstrated positive staining for alpha‐fetoprotein and alpha‐1‐antitrypsin. In addition, there was immunoreactivity with polyclonal carcinoembryonic antigen (CEA) antiserum in a canalicular pattern, focal staining for inhibin, oestrogen and progesterone receptors and absence of immunoreactivity for CK7 that contrasts with the immunophenotype of a usual yolk sac tumour.

Conclusions

Ovarian H‐YST and hepatocellular carcinoma share a similar immunoprofile. Ovarian H‐YST is a highly aggressive tumour, most patients exhibit recurrence or die of disease within 2 years of diagnosis.
A novel immunohistochemical detection system using mirror image complementary antibodies (MICA)
Authors: Mangham D C , Isaacson P G
Published: March 2003

Aims

To describe and illustrate a novel and highly sensitive peroxidase‐based immunohistochemical detection system which employs mutually attractive, mirror image complementary antibodies (MICA).

Methods and results

To demonstrate the sensitivity of the MICA system alongside the avidin–biotin complex (ABC) method, we selected a range of mouse monoclonal and rabbit polyclonal primary antibodies against antigens that are generally regarded as relatively difficult or impossible to detect on formalin‐fixed, paraffin‐embedded lymphoid tissue. Compared with the ABC method, the MICA immunodetection method enabled us to dilute primary antibodies up to 200‐fold with equivalent or superior immunostaining results and, usually, considerably shortened primary antibody incubation times.

Conclusions

We have described and illustrated a novel immunohistochemical detection system and demonstrated greatly increased sensitivity over the commonly used ABC system. An additional advantage of the MICA system is that it is avidin‐free and so avoids non‐specific staining due to endogenous tissue biotin.
Pleomorphic adenomas of the parotid express different mesenchymal phenotypes: demonstration of matrix gene expression products characteristic of the fibroblastic and chondrocytic cell lineages
Authors: Neureiter  , Böhmer  , Kirchner  , Aigner
Published: March 2003

Aims

Pleomorphic adenomas of the salivary glands are characterized by their high tissue diversity. Many studies have explored the derivation and differentiation of the neoplastic cells. We investigated the composition of the collagenous extracellular tumour matrix and could show a specific biochemical composition pattern in the different tumour areas.

Methods and results

In epithelially differentiated acinar and ductal areas there was positive staining for basement membrane collagen type IV and no, or only scarce, staining for collagen types I, II, III, or VI. Solid areas mostly lacked any extracellular matrix. In areas with fibrous tissue‐like appearance, the fibroblast‐typical interstitial collagen types I, III and VI were seen. Chondroid areas showed abundantly the characteristic cartilage components, collagen type II and, pericellularly, type VI collagen.

Conclusions

Our data show the presence of fibroblastic and chondrocytic cell differentiation in pleomorphic adenomas. Thus, they confirm that these neoplasms display, besides epithelial cell types, also real mesenchymal cell and tissue types. Differences in the abundance and the biochemical composition of the extracellular tumour matrix account largely for the morphological heterogeneity of pleomorphic adenomas of the salivary glands.
Atypical lobular hyperplasia and lobular carcinoma in situ: surgical and molecular pathology
Authors: Lishman  , Lakhani
Published: March 2003

Lobular carcinoma in situ and atypical lobular hyperplasia were first described over 50 years ago. Despite this long incubation period, the biological nature of the lesions remains controversial. They are generally regarded as ‘risk indicators’ of invasive cancer rather than true precursor lesions. When first described, the ‘carcinoma in situ’ designation implied radical treatment in the form of a mastectomy. Subsequent observation has shown that the lesions are often multifocal and bilateral. The risk to the woman of developing invasive cancer after a diagnosis of lobular carcinoma in situ is small. Hence, the lesion has increasingly been regarded as a ‘hyperplastic’ proliferation, which although predicting for subsequent risk of invasive cancer, does not in itself need treatment. In this review, we challenge this view and explore the developments in the understanding of this controversial entity.
Primary alveolar soft part sarcoma of bone
Authors: Park  , Unni  , Kim  , Han  , Yang  , Wenger  , Sim  , Lucas  , Ryan  , Nadim  , Nojima  , M Fletcher
Published: March 2003

Aims

Alveolar soft part sarcoma is a distinct, rare soft tissue tumour occurring primarily within the skeletal muscles or musculofascial planes in young adults. Primary involvement of bone is extremely rare. We report on six patients with alveolar soft part sarcoma occurring primarily in bone.

Methods and results

Thorough clinical and radiographic examinations were done to rule out any other primary site. The patients were four women and two men aged 17–35 years (mean, 24.5 years). The primary site of the tumour was the femur in three patients, the ilium in one and the fibula in two. In one of the patients with fibular involvement, the tibia was also involved by direct extension. Of the long bone lesions, three were centred in the metaphysis and one in the diaphysis. Radiographically, all of the lesions demonstrated an osteolytic pattern of bone destruction with ill‐defined margins and a wide zone of transition between the lesion and adjacent normal bone. Microscopically, all tumours showed the typical histological pattern of alveolar soft part sarcoma. Diastase‐resistant, periodic acid–Schiff‐positive crystalline structures were identified within the cytoplasm and confirmed ultrastructurally. Immunohistochemically, a keratin stain was negative in all cases; there was positive staining for MyoD1 in the cytoplasm but not the nuclei. Distant metastasis developed in four patients; one died.

Conclusion

Alveolar soft part sarcoma arising in bone is extraordinarily rare but should be considered in the differential diagnosis of metastatic hypernephroma in a young patient.
Thyroid transcription factor‐1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B
Authors: Kaufmann  , Dietel
Published: March 2003

Aims

Antibodies against the thyroid transcription factor‐1 (TTF‐1) and the surfactant proteins A and B (SPA, SPB) were compared as paraffin‐reactive immunohistochemical markers for non‐small cell carcinomas of pulmonary origin.

Methods and results

We studied 138 carcinomas of pulmonary origin (98 adenocarcinomas, 20 non‐neuroendocrine large cell carcinomas, 20 squamous cell carcinomas) and a total of 276 extrapulmonary carcinomas of various primary origins. Using the monoclonal antibody 8G7G3/1, TTF‐1 was detectable in 75% of non‐mucinous pulmonary adenocarcinomas and in 40% of large cell carcinomas but in only 10% of mucinous adenocarcinomas and not in squamous cell carcinomas. In contrast, both SPA and SPB were positive in only 45% of pulmonary adenocarcinomas and in 10% and in 5% of the large cell carcinomas, respectively. TTF‐1 had a specificity of 0.98 for pulmonary carcinomas as 5/7 thyroid carcinomas were the only TTF‐1‐positive extrapulmonary tumours. Anti‐SPB and anti‐SPA had specificities of 1.00 and 0.97, respectively.

Conclusions

The monoclonal antibody 8G7G3/1 against TTF‐1 should be the first choice as a component of an antibody panel aiming to prove or to exclude the pulmonary origin of non‐mucinous adenocarcinomas and non‐neuroendocrine poorly differentiated carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site.
Epstein–Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV‐positive and negative tumours
Authors: Chapel  , Fabiani  , Davi  , Raphael  , Tepper  , Champault  , Guettier
Published: March 2003

Aims

The presence of Epstein–Barr virus (EBV) was studied in 56 gastric carcinomas from Western patients by in‐situ hybridization for EBV‐encoded RNAs (EBER). EBV‐positive and negative carcinomas were compared for various pathological parameters including p53 overexpression.

Methods and results

EBERs transcripts were detected in seven cases overall: four cases of 52 conventional carcinomas (7.7%) and three cases of four gastric carcinomas with lymphoid stroma (75%). EBER positivity was diffuse in five cases and restricted to a localized area of the tumour in two cases of conventional carcinoma. A monoclonal EBV genomic pattern was demonstrated in the case tested by Southern blot analysis. By immunohistochemical analysis, neither EBV latent or lytic cycle proteins nor C3d/EBV receptor were expressed by neoplastic cells. EBER positivity was significantly correlated with prominent lymphoid reaction (P = 0.0002) which was associated with numerous PS100‐positive dendritic cells and with HLA‐DR expression by tumour cells (P = 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV‐negative cases and was absent in EBV‐positive cases except in one case with focal EBER‐positivity.

Conclusions

Focal staining for EBER is an unusual finding in the setting of gastric carcinoma and these results suggest that there might be two types of EBV‐associated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen‐presenting ability by HLA‐DR‐positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV‐associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV‐negative cases.
Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases
Authors: Denley  , Pinder  , Tan  , Sim  , Brown  , Barker  , Gearty  , Elston  , Ellis
Published: March 2003

Aims

This study presents a series of five cases in which metaplastic carcinoma, predominantly low‐grade adenosquamous carcinoma, of the breast is seen arising within a background of a complex sclerosing lesion. This association has been recognized previously but has not been documented in detail. This study describes the characteristics of the components present in each case and discusses the existing literature. This observation adds further evidence to support an association between some types of invasive breast carcinoma and sclerosing lesions of the breast.

Methods and results

Four of these cases were received as referral cases for opinion. The fifth was received as part of the routine surgical workload within our own institution. Two patients presented following mammographic screening and three symptomatically; their mean age was 62 years (range 49–68). The mean lesion size was 16 mm (range 7–24). All five lesions showed features of a complex sclerosing lesion/radial scar in the form of central sclerosis with elastosis and radiating benign entrapped tubules. One had associated benign papillary structures and two had focal benign squamous mletaplasia. Four cases showed coexisting but distinct areas of low‐grade adenosquamous carcinoma with glandular and squamous epithelial differentiation in a spindle cell background. One case had associated undifferentiated spindle cell carcinoma. Detailed immunophenotypic characteristics of two cases are presented.

Conclusions

This series illustrates a postulated but previously unconfirmed association between an unusual form of metaplastic breast carcinoma (adenosquamous carcinoma) and complex sclerosing lesions. The mechanisms of induction of breast carcinoma are poorly understood but these observations further emphasize the potential for sclerosing lesion of the breast to be associated with, and possibly give rise to, invasive carcinoma of different types. The precise nature of the interaction between the pathological processes remains unclear.