bluuebunny/crossref_metadata_2025 huggingface dataset:
Human platelets express hemochromatosis protein (HFE) and transferrin receptor 2
Authors: Hannuksela Jokke , Parkkila Seppo , Waheed Abdul , Britton Robert S. , Fleming Robert E. , Bacon Bruce R. , Sly William S.
Published: December 2004

Abstract: Objectives: While body iron status may influence platelets, little information is available about platelet expression of proteins regulating iron homeostasis. HFE, the protein defective in hereditary hemochromatosis, and transferrin receptor 2 (TfR2) are two novel protein candidates that could be involved in mechanisms of iron transport across the platelet plasma membrane.

Methods: The expression and localization of HFE, TfR1 and TfR2 proteins in human platelets were examined using Western blotting and immunocytochemistry.

Results: Human platelets expressed HFE and TfR2, whereas no signal for TfR1 was found. The positive reactions for HFE and TfR2 were mainly confined to the platelet plasma membrane.

Conclusions: Expression of HFE and TfR2 proteins in human platelets may indicate that the mutations in the corresponding genes could influence platelet count, size and/or activation. The presence of TfR2 and absence of TfR1 suggests that HFE may serve a different function in platelets compared with the other HFE‐positive cell types, e.g. enterocytes, macrophages and syncytiotrophoblasts.
Differentiation of follicular dendritic sarcoma cells into functional myeloid‐dendritic cell‐like elements
Authors: Porta Matteo Della , Rigolin Gian Matteo , Bugli Anna Maria , Bardi Antonella , Bragotti Letizia Zenone , Bigoni Renato , Cuneo Antonio , Castoldi Gianluigi
Published: December 2004

Abstract: In a rare case of follicluar dendritic cell sarcoma, malignant cells were isolated and cultured in the presence of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin 4 (IL‐4) and tumor necrosis factor alpha (TNF‐α). After 14 d, 15% of neoplastic cells differentiated into myeloid‐dendritic cell‐like elements as demonstrated by immunological and functional characteristics.

These cells showed the same cytogenetic abnormality of the malignant clone (fluorescence in situ hybridisation analysis performed on CD1a+ cells) and were able to induce allogenic T‐cell proliferation in the mixed leucocyte reaction.

These data may indicate that antigen presenting capacity could be a functional state inducible in cellular elements which are believed not to be of hemopoietic origin.

Further studies are warranted to confirm these findings and to clarify the possibility to use these cells to generate specific anti‐tumoral immune responses.
Emergence of Philadelphia positive chronic myeloid leukaemia during treatment with hydroxyurea for Philadelphia negative essential thrombocythaemia
Authors: Wahlin Anders , Golovleva Irina
Published: December 2004

A 58‐yr‐old male patient with essential thrombocythaemia (ET) developed chronic myeloid leukaemia (CML) after continuous uneventful treatment with hydroxyurea for 18 yr. G‐banding analyses of bone marrow cells had repeatedly demonstrated normal male karyotype before this event, but t(9;22)(q34;q11) was demonstrated after the event. An unrelated allogeneic stem cell transplantation was performed. Blood and bone marrow morphology, and the karyotype were normalised and the patient is in good health 1 yr post‐transplant. There are no previous reports in the literature about the emergence of CML during treatment with hydroxyurea.
Salvage treatment with etoposide (VP‐16), ifosfamide and cytarabine (Ara‐C) for patients with recurrent primary central nervous system lymphoma
Authors: Arellano‐Rodrigo Eduardo , López‐Guillermo Armando , Bessell Eric M. , Nomdedeu Benet , Montserrat Emili , Graus Francesc
Published: December 2004

Abstract:  Background: Survival of patients with primary central nervous system lymphoma (PCNSL) has improved with methotrexate‐based combination regimens and radiotherapy (RT). However, the prognosis of patients who fail or relapse after initial response is poor. Very little data is available on salvage treatment at recurrence.

Patients and methods: Sixteen immunocompetent patients (13 males/three females, median age 54 yr) with refractory (one patient) or recurrent (15 patients) PCNSL, homogeneously treated at diagnosis with the cyclophorphamide, doxorubicin, Vimcritime, dexamethasome/carmuntime, Uimcritime, cytarabine and methotrexate (CHOD/BVAM) and RT regimen, received etoposide (VP‐16), ifosfamide and cytarabine (Ara‐C) (VIA) chemotherapy as a salvage treatment. VIA included etoposide 100 mg/m2/d days 1–3, ifosfamide 1000 mg/m2/d days 1–5, and cytarabine 2000 mg/m2/12 h day 1. The therapy was repeated every 28 d for a total of planned six cycles.

Results: Median time between first complete response (CR) and relapse was 19 months (range: 6–46 months). Thirteen patients (81%) had a performance status ≤2, six had multifocal PCNSL and six (of eight tested) positive cerebrospinal fluid cytology. The median number of courses per patient was four (range: 1–6). Five patients completed the whole VIA therapy. Six patients (37%) achieved CR. After a median follow‐up of 15 months for surviving patients, two have relapsed, with a median failure‐free survival of 5 months. Twelve patients have died from progression of PCNSL, with a 12‐month overall survival of 41% [95% confidence interval (CI): 16–66]. The major toxicity was World Health Organization grade 2–4 neutropenia (69% of patients) and thrombocytopenia (50%). Five patients had grade 3–4 infectious complications. Finally, one patient developed a severe but reversible ifosfamide encephalopathy.

Conclusion: The data presented show that the chemotherapy VIA is an effective salvage regimen for patients with recurrent PCNSL.
Enzyme replacement therapy reduces Gaucher cell burden but may accelerate osteopenia in patients with type I disease – a histological study
Authors: Rudzki Zbigniew , Okoń Krzysztof , Machaczka Maciej , Rucińska Małgorzata , Papla Bolesław , Skotnicki Aleksander B.
Published: December 2004

Enzyme replacement treatment (ERT) is effective in controlling the clinical and biochemical manifestation of type I Gaucher disease. Little is known on the evolution of bone marrow histology caused by ERT. We compared the pretreatment trephine bone marrow biopsies in five patients (F32, F41, F50, M55, and M46) with the control biopsies performed after 26–32 months of imiglucerase treatment. The planimetric estimates revealed significant decrease in Gaucher cell burden in all the patients. The post‐ERT values ranged from 24% to 65% of the initial total volumes occupied by the Gaucher cells. This resulted mainly from disappearance of Gaucher cells, and to a lesser extent from their shrinkage. Normal hemopoiesis was markedly increased in four of five patients, fat tissue in all the five patients. Surprisingly, the estimated volumes of trabecular bone in the control biopsies were significantly smaller than in the pre‐ERT trephines (0.61%, 0.64%, 0.64%, 0.97%, and 0.22% of the initial volumes, P = 0.043). The bone loss correlated rather with the degree of reconstitution of normal hemopoiesis than with the decrease in the Gaucher cell burden. The histological response did not correlate strictly with initial clinical parameters and the genotype, with different reactions to ERT in two sibs (cases 3 and 4). Particularly, ERT alleviated bone manifestations in all four patients with previous bone pains or fractures. ERT may accelerate progress of osteopenia in men and premenopausal women. The clinical significance of this phenomenon remains to be established. Its mechanism may be linked to increased osteolytic activity exerted directly or indirectly by regenerating hemopoietic cells.
Treatment of pure red cell aplasia and autoimmune haemolytic anaemia in chronic lymphocytic leukaemia with Campath‐1H
Authors: Rodon Philippe , Breton Philippe , Courouble Gery
Published: December 2004

Abstract: A patient with chronic lymphocytic leukaemia (CLL) progressive on fludarabine therapy and life‐threatening anaemia related to immune haemolysis and pure red cell aplasia was treated with Campath‐1H. The patient had sustained complete remission of both CLL and anaemia, but died of recurrent sepsis and cachexia 10 months after completion of the treatment. Campath‐1H (alemtuzumab), a humanised anti‐CD52 monoclonal antibody, is a potent therapeutic agent against advanced CLL and immune cytopenias. It could be indicated in the treatment of severe immune complications of CLL unresponsive to corticosteroids. Prolonged immunosuppression is a serious side‐effect leading to severe infectious complication.
Replantation with intentional rotation of a complete vertically fractured root using adhesive resin cement
Authors: Kudou Yoshiyuki , Kubota Minoru
Published: December 2004

Abstract  – This case describes intentional replantation with rotation of a complete vertically fractured root using adhesive resin cement. The fractured root was fixed with adhesive resin cement extra‐orally. The tooth was replanted into the socket with rotation in order to avoid contact with the area where the periodontal ligament of the root surface was lost and the area where the alveola bone was lost along the fracture line. At follow‐up 18 months later, the tooth was asymptomatic and radiographically showed an increase in the density of the alveolar bone, and the periodontal pockets were improved.
Effect of internal bleaching agents on dentinal permeability of non‐vital teeth: quantitative assessment
Authors: Carrasco Laise Daniela , Fröner Izabel Cristina , Corona Silmara Aparecida Milori , Pécora Jesus Djalma
Published: December 2004

Abstract – The aim of thisin vitrostudy was to assess quantitatively dentin permeability of pulpless teeth after intracoronal bleaching therapy with three different agents. Twenty‐four maxillary central incisors were randomly assigned to four groups according to the bleaching agent used: I – non‐bleached control; II – 37% carbamide peroxide; III – sodium perborate/20% hydrogen peroxide paste; IV – 27% carbamide peroxide. After standard access and root‐canal preparation the access opening, biomechanical preparation and root‐canal filling, a cervical glass ionomer plug was prepared and intracoronal bleaching procedures were carried out in a standardized fashion. The access cavities were opened and the teeth were externally sealed and immersed in a 10% copper sulfate aqueous solution for 30 min, in vacuum for the first 5 min. Then, samples were removed, dried with absorbing paper and immersed in a 1% rubianic acid alcohol solution, for the same above‐mentioned period in solution and in vacuum. Copper ion penetration was indicated by the rubianic acid staining. Mean values and SD for the experimental groups were: I – 7.88% (±1.33), II – 16.94% (±5.72); III – 11.45% (±3.90) and IV – 8.98% (±4.19). Data were submitted to one‐wayanova. The results showed that the 37% carbamide peroxide provided the highest increase in dentin permeability, followed by sodium perborate with 20% hydrogen peroxide. The 27% carbamide peroxide provided the lowest results and showed statistical similarity to the control group. On basis of these findings, it may be concluded that, among the tested intracoronal bleaching agents, 37% carbamide peroxide presented an optimized overall performance in increasing dentinal permeability.
Bone regeneration after surgical repositioning of impacted mandibular second molars: a case report
Authors: Shipper Guy , Thomadakis George
Published: December 2004

Abstract  – A case is presented where the mesially impacted mandibular second molar teeth were surgically uprighted in an 11‐year‐old female patient. Bone regeneration is shown in the areas occupied by the impacted second molars with maturation of bone and cortication of the crest of the alveolar bone. The probing depths are also normal with no residual bony defects. This healing was achieved with no bone grafting procedure, emphasizing two important factors: to prevent/minimize any trauma to the tissues at the site of elevation and uprighting of the tooth (i.e. maintaining viable periodontal ligament cells and minimal cementum damage); and to obtain primary closure whilst allowing the tissue in the mesial defect to reorganize against the scaffold of bone. However, the procedure on the one side was complicated with necrosis and infection of the pulp space with external inflammatory root resorption. Endodontic therapy of this tooth proved to be successful with periradicular healing radiographically and re‐establishment of the lamina dura. At the 3‐year follow‐up, the endodontically treated tooth showed no clinical and radiographic signs of pathology. The left second mandibular molar had no pulpal or periodontal postsurgical complications, which may be attributed to apparently more open apices allowing for pulp revascularization after manipulation at the time of surgery. This report illustrates unassisted wound healing that occurs in the area of uprighting with complete reconstitution of periodontal anatomy without additional regenerative procedures to augment bone.
The effect of topical minocycline on replacement resorption of replanted monkeys' teeth
Authors: Ma Khin Ma , Sae‐Lim Varawan
Published: December 2004

Abstract  – Tetracycline has been reported to possess antiresorptive properties in addition to antimicrobial actions. Systemic administration of tetracycline showed variable results in the control of replacement resorption after replantation with good results in half of the cases, and almost no healing in the rest. The purpose of this study was to evaluate histologically the effect of topically applied minocycline on replacement resorption of replanted monkeys' teeth. Thirty‐two roots from seven monkeys were endodontically treated aseptically to prevent inflammatory resorption of pulpal origin, a common sequela after avulsion injury. Teeth were then extracted as atraumatically as possible. Teeth in the negative control group (10 roots) were replanted almost immediately, while teeth in the positive control group (12 roots) were allowed to bench‐dry for 1 h prior to replantation, both without further treatment. Teeth in the experimental group (10 roots) were bench‐dried for 1 h, rinsed with saline, and then immersed in 1 ml of 50 mg ml−1 minocycline hydrochloride for 5 min before replantation. No splinting was used. After 12 weeks, the animals were sacrificed and histological sections were prepared and evaluated according to a morphometric analysis modified from that described by Andreasen (1987) as complete healing, inflammatory resorption, and replacement resorption. Kruskal–Wallis test showed significant differences among the three groups in all the three healing categories. Further analysis with Mann–Whitney U‐test showed teeth in the negative control group to have significantly higher complete healing and significant lower unfavorable healing, comprising of replacement resorption and inflammatory root resorption than the positive control group and the minocycline group. Topical application of minocycline to the root surface appeared to result in slightly higher occurrence of complete healing (32.46%) compared to the delayed replantation group with no minocycline treatment (positive control) (16.58%), but the difference was not statistically significant (P = 0.09).
Genetic epidemiology of amyotrophic lateral sclerosis
Authors: Majoor‐Krakauer D , Willems PJ , Hofman A
Published: December 2004

Amyotrophic lateral sclerosis (ALS) is a late onset, rapidly progressive and ultimately fatal neurological disorder, caused by the loss of motor neurons in the brain and spinal cord. Familial aggregation of ALS, with an age‐dependent but high penetrance, is a major risk factor for ALS. Familial ALS (FALS) is clinically and genetically heterogeneous. Three genes and linkage to four additional gene loci have been identified so far and may either predominantly lead to ALS (ALSI‐ALS6) or cause multisystem neurodegeneration with ALS as an occasional symptom (tauopathies, ALS‐dementia complex). This review presents a tentative classification of the “major” ALS genes and ALS “susceptibility” genes, that may act as susceptibility factors for neurodegeneration in interaction with other genetic or environmental risk factors. Considering that mutations in ALS genes explain approximately 10% of familial as well as sporadic ALS, and most remaining cases of the discase are thought to result form the interaction of several genes and environmental factors, ALS is a paradigm for multifactorial discases.
Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia
Authors: Al‐Shali K , Wang J , Rosen F , Hegele RA
Published: December 2004

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder that is characterized by defective assembly and secretion of plasma apolipoprotein (apo) B‐containing lipoproteins. This disorder results from mutations in the MTP gene encoding the microsomal triglyceride transfer protein. We report a 58‐year‐old male homozygote for a missense mutation, S590I, in MTP. The patient had a lifelong history of fat malabsorption, but was only diagnosed with ABL at age 52, based upon such classic features as absence of apo B‐containing lipoproteins, acanthocytosis, atypical retinitis pigmentosa and markedly depressed serum beta‐carotene concentration. However, his presentation was notable not only by survival to the sixth decade of life without specific treatment, but also by the absence of neurological involvement and by normal serum vitamin E concentration. He subsequently developed adenocarcinoma of the ileum, which required ileal resection. Therefore, this missense mutation appears to be associated with a late‐presenting and relatively mild ABL phenotype that lacks some classical features, particularly neuropathy, but appears to be associated with other atypical features, specifically small intestinal cancer.
Altered cytokeratin expression in actinic cheilitis
Authors: Dos Santos Jean N. , De Sousa Suzana O. M. , Nunes Fábio D. , Sotto Miriam N. , De Araújo Vera C.
Published: December 2004

Background:  Actinic cheilitis (AC) is a widely recognized precancerous lesion of the lip. Varying degrees of epithelial dysplasia may be present. However, no studies have correlated epithelial changes with cytokeratin expression that might reflect the disordered maturation that is probably occurring.

Methods:  Thirty‐four cases diagnosed as AC were classified according to dysplasia degree, and submitted to immunohistochemical staining for the detection of cytokeratins (CKs) 7, 8, 13, 14, 16 and 19. Normal mucosa adjacent to the lesions was also evaluated.

Results:  The results obtained showed that CK10 immunostained only superficial keratinized epithelial layers in 11 cases, and also intermediate spinous layers in 18 cases. Cytokeratin 14 was expressed in all epithelial layers of 31 cases, in two cases its expression was in the basal and intermediate layers, and one case was negative. Cytokeratin 13 immunostained 26 cases and was negative in eight cases. In these eight cases, CK13 was apparently replaced by CK16. Cytokeratin 16, besides these eight cases, was also expressed in the spinous intermediate layers of a further eight cases. The remaining CKs tested were all negative. No relation between the degree of dysplasia and the CK expression was noted.

Conclusions:  Cytokeratin expression in AC is different from that of normal oral mucosa, and is not related to the degree of dysplasia.
Sweet syndrome in multiple myeloma: a series of six cases
Authors: Bayer‐Garner I. B. , Cottler‐Fox M. , Smoller B. R.
Published: December 2004

Background:  Sweet syndrome (SS), a paraneoplastic syndrome characterized by fever, neutrophilia, multiple erythematous painful plaques, and a dense dermal neutrophilic infiltration, has a known association with hematologic malignancies such as acute myelogenous leukemia. However, no clear association with multiple myeloma (MM) has been reported.

Materials and methods:  Pathology reports of the 2357 patients with multiple myeloma at the University of Arkansas for Medical Sciences were reviewed to retrieve cases who had developed SS. Cytogenetic studies and immunoglobulin secretory status were retrieved. Five cases of SS in MM and 25 cases of SS in patients without MM underwent syndecan‐1 immunohistochemistry.

Observations:  Six cases of SS occurring in the setting of MM showed a predominance in patients secreting IgG paraprotein. Five of the six patients received granulocyte‐colony stimulating factor while the sixth received granulocyte‐monocyte‐colony stimulating factor. Fifty percent showed a non‐specific cytogenetic anomaly.

Conclusions:  There is no specific cytogenetic anomaly associated with SS in the setting of MM. This paraneoplastic syndrome may be secondary to elevated levels of granulocyte colony stimulating factor (G‐CSF), possibly with a component of enhanced sensitivity to endogenous G‐CSF. The immunoglobulin secretory status parallels that seen in MM with cutaneous involvement, but IgG secretors may be at an increased risk of developing SS compared with their counterparts who secrete other immunoglobulins.
The APOPTOSIS of dermatopathology?
Authors: Bhawan Jag
Published: December 2004

It is a privilege and an honor for me to have served as your president in this past year and to have the opportunity to address you today. In this presentation, I am using the term ‘APOPTOSIS’ as an acronym (Fig. 1). I do not necessarily mean to imply apoptosis here in its literal meaning; you may well infer it to be so after listening to my presentation and your own personal experience. For reasons of logic, I will not be discussing the various letters in order.

Apoptotic cells are seen in the epidermis on the right in a patient with sunburn. Various topics under ‘APOPTOSIS’ are listed on the left.

image
Intraepidermal neutrophils – a clue to dermatophytosis?
Authors: Meymandi Simin , Silver Shane G. , Crawford Richard I.
Published: December 2004

Background:  Dermatophyte infections are occasionally diagnosed by histopathology. Spongiotic or psoriasiform features are typical but non‐specific, and neutrophils may be present within the stratum corneum. Traditionally, this latter finding has been felt to be a diagnostic clue for dermatophytosis, and usually precipitates a periodic acid Schiff (PAS‐D) stain to confirm the presence of hyphae in the stratum corneum. Our objective was to evaluate whether the presence of neutrophils within the stratum corneum is a sensitive or specific test for dermatophytosis.

Methods:  We performed a retrospective case–control study on 303 cases of spongiotic or psoriasiform dermatitides over a 35‐month period. Hematoxylin and eosin (H&E) and PAS‐D stains were utilized to identify intraepidermal neutrophils and fungi.

Results:  The sensitivity and specificity for diagnosing dermatophyte infection based upon neutrophils within the stratum corneum were 62 and 59%, respectively. The positive and negative predictive values in our population were 4 and 98%, respectively.

Conclusion:  The histologic feature of neutrophils within the stratum corneum is neither sensitive nor specific in the diagnosis of dermatophytosis.
Clear cells of Toker in accessory nipples
Authors: Willman Joseph H. , Golitz Loren E. , Fitzpatrick James E.
Published: December 2004

Background:  Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Paget's disease (EMPD), although the distribution of Toker cells outside of the nipples has not been studied. Using immunohistochemistry, we studied 20 cases of accessory nipples for the presence of Toker cells.

Methods:  A retrospective study of 20 cases of accessory nipples was performed using routine hemotoxylin and eosin staining, as well as immunohistochemical staining for CK7, CK20, EMA, and GCDFP‐15.

Results:  Thirteen out of 20 accessory nipples (65%) demonstrated Toker cells with CK7 staining. Toker cells in six of the 13 cases were also positive for EMA. Only one case with Toker cells showed immunoreactivity for antibodies to GCDFP‐15.

Conclusions:  Toker cells occur outside the normal nipple epidermis in the epidermis of accessory nipples. The distribution of Toker cells along the milk line correlates with the distribution of most cases of EMPD along the milk line, especially in the groin and axillae. Further studies are necessary to define the relationship between Toker cells and EMPD.
A novel technique for the examination of skin biopsies by laser capture microdissection
Authors: Agar N. S. , Halliday G. M. , Barnetson R. St C. , Jones A. M.
Published: December 2004

Background:  Skin is an inherently heterogeneous tissue, thus the procurement of pure cell populations is critical for the accurate correlation of a molecular profile to a particular cell type or histological location. Laser Capture Microdissection (LCM) permits the efficent procurement of cells and mapping of genetic changes from histologically prepared samples.

Methods:  This paper describes a robust LCM protocol established in our laboratory for the extraction of high quality DNA which sequenced from 100% of microdissected samples without the need for cloning. The unique properties of skin, in particular its strong intercellular adhesive forces, have dictated a significant modification to the normal procedure of tissue preparation to ensure reliable cell procurement.

Results:  Using the methods outlined below we were able to precisely map the pattern of genomic mutations in our target gene of interest in normal skin, actinic keratosis and squamous cell carcinoma.

Conclusions:  The capability to select pure cell populations from the skin will revolutionise our ability to understand the processes involved in cutaneous tumourigenesis.
Mycosis fungoides‐like reaction in a patient treated with Gleevec
Authors: Clark Sandra H. , Duvic Madeleine , Prietol Victor G.
Published: December 2004

Background:  Gleevec™ is a protein tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Currently, Gleevec is also being used in protocols for treatment of other malignancies such as melanoma. A few, non‐descript cutaneous eruptions have been reported in patients receiving Gleevec.

Case report:   A patient with a gastrointestinal stromal tumor developed a centripetal, slightly pruritic, predominantly macular eruption. Histologically, there was a superficial and mid‐perivascular cellular infiltrate of hyperchromatic, large lymphocytes with focal epidermotropism, thus resembling mycosis fungoides. The infiltrate was composed predominantly of T cells (CD3), with a 1:1 CD4:CD8 ratio, therefore consistent with a reactive process, i.e. a drug reaction induced by Gleevec.

Conclusion:  Gleevec should be considered in the differential diagnosis of pseudolymphoma drug eruptions.
Actin expression in purely nodular versus nodular‐infiltrative basal cell carcinoma
Authors: Law Allison M. , Oliveri Cecilia V. , Pacheco‐Quinto Xavier , Horenstein Marcelo G.
Published: December 2004

Background:  The prognosis of basal cell carcinoma (BCC) correlates with its histological subtype. Actin is a microfilament that contributes to cell motility and invasiveness of cancer cells. Actin has been found to be more prominently expressed in the tumor cells and stroma of the more aggressive BCC subtypes. Here we compare actin expression in purely nodular (N‐BCC) versus nodular‐infiltrative (NI‐BCC) tumors.

Methods:  We studied seven cases of N‐BCC and 13 cases of NI‐BCC with immunohistochemistry for alpha‐smooth muscle actin (SMA) and common muscle actin (CMA) within the tumor cells and stroma. A semiquantitative method was used to determine the degree of actin present in the tumor aggregates (on a scale of 0–4).

Results:  Actin was present in the nodular component of 2/7 (28%) purely N‐BCC and 11/13 (85%) mixed NI‐BCC (p = 0.001). Actin was present in the infiltrative component of 13/13 (100%) NI‐BCC. The average SMA score was 0.57 within the N‐BCC compared with 1.77 within the nodular component of NI‐BCC (p = 0.04); and 2.46 within the infiltrative component of the NI‐BCC. The CMA score was 0.57 within the N‐BCC, 1.54 within the nodular component of NI‐BCC, and 1.92 within the infiltrative component of the NI‐BCC. Actin was not found in the stroma of any of the N‐BCC, while it was present in 8/13 (62%) of the NI‐BCC (p = 0.0009).

Conclusions:  Actin expression is more prominent in the nodular component of mixed NI‐BCC when compared with purely N‐BCC. This suggests that the nodular components of NI‐BCC and N‐BCC are different, and that actin expression in the nodular component may be associated with potential invasiveness. This finding may be relevant when examining incompletely sampled nodular BCC.
Differences in BCL‐XL expression and STAT5 phosphorylation in chronic myeloid leukaemia patients
Authors: Gutiérrez‐Castellanos Sergio , Cruz Miguel , Rabelo Laura , Godínez Rocio , Reyes‐Maldonado Elba , Riebeling‐Navarro Carlos
Published: December 2004

Chronic myelogenous leukaemia (CML) cells show expression of BCL‐XL, an anti‐apoptotic oncogene. This expression is induced by BCR‐ABL protein kinase through activation of the signal transducer and activator of transcription‐5 protein (STAT5). To date, however, the contribution of BCL‐XL and STAT5 to the transforming phenotype in CML is still unclear. This study was aimed at defining the status of activated STAT5 and BCL‐XL expression and their relation to BCR‐ABL rearrangement in CML cells derived from patients at different clinical stages. Twenty‐seven consecutive patients with CML were enrolled in the study. Peripheral blood mononuclear cells were lysed and subjected to immunoprecipitation and Western blotting to analyse phosphorylated STAT5. The p210 BCR‐ABL rearrangements were determined by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and BCL‐XL expression by semi‐quantitative RT‐PCR. We found that increased transcription of BCL‐XL gene was associated with phosphorylated STAT5 in the majority of blast crisis patients and in a few accelerated and chronic phase patients. Moreover, BCL‐XL expression levels were found to be decreased in chronic phase, contrary to a marked increase in blast crisis. We found no difference in expression of BCL‐XL and phosphorylated STAT5 when related with b3a2 and b2a2 BCR‐ABL rearrangements. These results suggest that STAT5 activity and BCL‐XL overexpression may reflect a stage of differentiation among CML phases, and this could contribute to BCR‐ABL‐dependent transformation.
Constitutive expression of the FK506 binding protein 51 (FKBP51) in bone marrow cells and megakaryocytes derived from idiopathic myelofibrosis and non‐neoplastic haematopoiesis
Authors: Bock Oliver , Neusch Michael , Büsche Guntram , Mengel Michael , Kreipe Hans
Published: December 2004

Objectives:  Overexpression of FK506 binding protein 51 (FKBP51) in megakaryocytic progenitor cells generated from purified CD34+ cells in patients with idiopathic myelofibrosis (IMF) has been demonstrated. It has been suggested that FKBP51 is involved in the dysregulation of the apoptotic programme with consecutive prolongation of cell survival. The knowledge of FKBP51 and its expression in bone marrow cells and mature megakaryocytes in non‐neoplastic haematopoiesis and IMF is sparse.

Methods:  To evaluate a potential overexpression of FKBP51 in patients with IMF (n = 37) compared with non‐neoplastic haematopoiesis (n = 31), total bone marrow cells as well as single megakaryocytes, isolated by laser microdissection, were quantitatively analysed by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR). By applying immunohistochemistry, FKBP51 gene expression was correlated with staining pattern and cellular localisation of the corresponding FKBP51 protein.

Results:  We demonstrated that FKBP51 is constitutively expressed in non‐neoplastic haematopoiesis. FKBP51 gene expression by total bone marrow cells as well as megakaryocytes was not significantly different in IMF. FKBP51 protein expression could be localised to myeloid progenitor cells as well as megakaryocytes. In particular, megakaryocytes were stained almost exclusively nuclear for FKBP51. No differences in expression patterns between both IMF and control cases could be demonstrated.

Conclusions:  For the first time, FKBP51 expression, in particular gene expression and subcellular localization was described in bone marrow cells of non‐neoplastic and neoplastic haematopoiesis grown in vivo. We conclude that FKBP51 could be temporarily overexpressed in megakaryocytic progenitors rather than contribute to the accumulation of mature megakaryocytes in IMF.
Can a therapeutic dose of amphetamine during pre‐adolescence modify the pattern of synaptic organization in the brain?
Authors: Diaz Heijtz Rochellys , Kolb Bryan , Forssberg Hans
Published: December 2004

Stimulant drugs such as amphetamine have, for many decades, been the drugs of choice in the treatment of children with attention‐deficit/hyperactivity disorder. However, little is known about their therapeutic mechanisms or about the consequences of their long‐term exposure. In the present study we investigated whether repeated exposure of a low dose of amphetamine (0.5 mg/kg) to juvenile rats could induce long‐term morphological alterations in the prefrontal cortex. In addition, to assess possible behavioural consequences of prolonged exposure to this drug, we examined whether changes in the motor response to various dopamine agonists occurred after this treatment. We found that this dose of amphetamine promotes plasma concentrations of amphetamine sulphate in juvenile rats to levels corresponding to the clinical range used for children with attention‐deficit/hyperactivity disorder. Amphetamine (0.5 mg/kg; s.c.) was administered twice daily during postnatal days 22–34, and then the brains of the animals were evaluated 2 weeks later. This treatment produced an increase in dendritic length and branches of pyramidal neurons of the medial prefrontal cortex, but not in the nucleus accumbens. These changes were associated with an increase in the expression of calcium/calmodulin‐dependent protein kinase II, a highly abundant signalling protein in the postsynaptic densities of excitatory synapses. Interestingly, amphetamine pre‐treatment did not alter the motor response to various dopamine agonists, including amphetamine. These data suggest that clinical doses of stimulant drugs may be acting as a trophic support at the glutamatergic synapses, thereby enhancing dopamine–glutamate interactions in the prefrontal cortex.
Cell cycle and apoptosis
Authors: Vermeulen Katrien , Berneman Zwi N. , Van Bockstaele Dirk R.
Published: December 2004

Abstract.  Apoptosis and proliferation are intimately coupled. Some cell cycle regulators can influence both cell division and programmed cell death. The linkage of cell cycle and apoptosis has been recognized for c‐Myc, p53, pRb, Ras, PKA, PKC, Bcl‐2, NF‐κB, CDK, cyclins and CKI. This review summarizes the different functions of the proteins presently known to control both apoptosis and cell cycle progression. These proteins can influence apoptosis or proliferation but different variables, including cell type, cellular environment and genetic background, make it difficult to predict the outcome of cell proliferation, cell cycle arrest or cell death. These important decisions of cell proliferation or cell death are likely to be controlled by more than one signal and are necessary to ensure a proper cellular response.
Acral myxoinflammatory fibroblastic sarcoma in FNAB samples: can we distinguish it from other myxoid lesions?
Authors: Pohar‐Marinšek Ž. , Fležar M. , Lamovec J.
Published: December 2004

We analysed cytomorphological characteristics of three fine needle aspiration biopsy (FNAB) samples of acral myxoinflammatory fibroblastic sarcoma (AMIFS) as well as the features of a number of other benign and malignant myxoid lesions. The analysis showed that FNAB samples from two cases of AMIFS had similar cytomorphology, containing all the characteristic features described in surgical biopsies: myxoid material, spindle cells with bipolar cytoplasmic extensions, epithelioid cells with globules of extra‐cellular material, ganglion‐like and lipoblast‐like giant cells. Only the inflammatory component was scarce. The third sample did not contain features typical of AMIFS. Samples from other myxoid tumours resembled AMIFS to some extent, however, none of them contained all three tumour components characteristic of AMIFS. Cytomorphology of AMIFS may be characteristic enough to enable a definitive diagnosis from FNAB, provided all the distinctive features are sampled.
An alternate model of thyroid cytology: practical not perfect
Authors: Holbrook M. R. , Kendall C. H. , Shaw P. A. V.
Published: December 2004

A sample of 384 thyroid cytology specimens prepared by cytospin over a 2.5‐year period was classified by original report into inadequate, non‐neoplastic and suspicious of neoplasia or worse. This was then compared with subsequent histology. The resulting data showed an inadequacy rate of 33%, a sensitivity of 55%, a specificity of 59%, a positive predictive value of 64% and a negative predictive value of 93%. On review of the cytology, in knowledge of the subsequent histology, the maximum achievable results were determined to have a positive predictive value of 79% and a negative predictive value of 97%. No clinically significant adverse event was detected.
Role of fine needle aspiration cytology in evaluation of paediatric lymphadenopathy
Authors: Handa U. , Mohan H. , Bal A.
Published: December 2004

Fine needle aspiration cytology (FNAC) in children has been slow to gain acceptance as compared with its use in adults. The aim of this retrospective study is to determine the utility of FNAC in diagnosing paediatric lymphadenopathy. Six hundred and ninety‐two paediatric lymph nodes were aspirated during the period from January 1996 to June 2001. Aspirated material in 32 cases (4.6%) was deemed inadequate for cytological diagnosis. In the remaining cases, 62.2% were reactive lymphadenopathy, 25.2% tuberculous lymphadenitis, 6.3% acute suppurative lymphadenitis, nine cases revealed malignancy (seven lymphoma, two metastatic deposits) and one case had Langerhan's cell histiocytosis. No significant complications were encountered in any of the cases. FNAC emerged as a safe and reliable diagnostic procedure in paediatric age group obviating the need for excision biopsy.
An audit of the positive predictive value of high‐grade dyskaryosis in cervical smears: 2001–2002
Authors: Wadehra V. , Johnson S. J.
Published: December 2004

The positive predictive value (PPV) of high‐grade dyskaryosis for cervical intraepithelial neoplasia grade 2 (CIN2) or worse on histology is published annually for the laboratories in the UK National Health Service Cervical Screening Programme (NHSCSP). The PPV fell in 2001 compared with 2000 for four of the five consultants reporting cervical smears in our laboratory, the greatest fall being from 91.6% to 77.9%. Investigation of the possible reasons for the fall suggested the main cause lay outside the laboratory in the type of biopsy taken at colposcopy. We conclude that biopsy type affects accuracy of PPV calculations. There is variation in collection and submission of KC61 data including PPV across laboratories. This factor needs to be taken into account when publishing and comparing laboratory data for the NHSCSP.
Examination for the Certificate in Advanced Practice in Cervical Cytology – the first year's experience
Authors: Smith P. A. , Hewer E. M.
Published: December 2004

Following the decision to establish an Advanced Biomedical Scientist Practitioner grade for senior biomedical scientists in the NHS Cervical Screening Programme, a conjoint examination board has been appointed by the Royal College of Pathologists and Institute of Biomedical Science to oversee the Certificate in Advanced Practice in Cervical Cytology examination. The examination consists of a multiple‐choice paper, short‐answer written questions and practical microscopy sections covering screening of unmarked slides, and more complex discussion cases. In the first year there were 58 entries with 29 successful candidates, a pass rate of 50%. The standard of performance in the examination showed a wide range, and some candidates appear to have underestimated the degree of preparation, knowledge or level of microscopy skill required.
The role of FNA in the initial management of thyroid lesions: 7‐year experience in a district general hospital
Authors: El Hag I. A. , Kollur S. M. , Chiedozi L. C.
Published: December 2004

Fine needle aspiration (FNA) cytology plays a major role in the diagnosis of the thyroid lesions in university hospitals and tertiary referral institutions. Our aim was to find out if this was possible in small district hospitals with limited resources. Over a 7‐year period, from October 1994 to April 2002, 303 patients with thyroid swellings underwent FNA with an overall adequacy rate of 97.7%. FNAs were performed specifically by the pathologists, so that our inadequacy rate, 2.3% was far lower than 11–29% reported elsewhere. The FNA findings were compared with subsequent histology results in 67 cases. The diagnosis of benign and neoplastic lesions was predicted accurately by FNA in 93% and 94.7% of cases, respectively. The latter reached 100% if results of FNA in follicular neoplasms were excluded. Sensitivity and specificity were 85.6% and 97.6%, respectively, which is comparable with results from tertiary institutions. The commonest thyroid lesions in our hospital were nodular goitre (52.4%), followed by thyroiditis (17.6%) and neoplasia (13.9%). We conclude that, with the availability of appropriate personnel, FNA is feasible as the major modality in district general hospitals. FNA in follicular lesions remains challenging but could be overcome in part by recognizing the criteria to differentiate follicular variant of papillary carcinoma and other follicular proliferations. Aspiration, smearing, staining and interpretation should be left to pathologists or other well‐trained personnel to ensure good quality and consistency.
Randomized controlled trial evaluating rapid pre‐screen of cervical cytology specimens
Authors: Saville M. , Mitchell H.
Published: December 2004

A randomized controlled trial of 75 355 cervical cytology specimens was performed comparing rapid pre‐screen with no pre‐screen. While the percentage of cases receiving a final report of definite high‐grade abnormality was higher in the no pre‐screen arm (no pre‐screen = 0.70%, pre‐screen = 0.65%), the percentage of cases receiving a final report of possible or definite high‐grade abnormality was essentially identical in the two arms of the trial (no pre‐screen = 1.22%, pre‐screen = 1.21%). In the randomized trial, one extra cytology report of definite high‐grade abnormality was made for every 12 568 slides pre‐screened. This level of benefit was reduced by about half when rapid pre‐screen was adopted as a routine laboratory practice.
Cytology suggestive of glandular neoplasia: outcomes and suggested management
Authors: Hare A. A. , Duncan A. R. , Sharp A. J.
Published: December 2004

Eighty‐three cases having a cervical smear result showing abnormal glandular cells were identified and matched up with the diagnostic histology result. Thirty‐four (41.0%) were associated with malignancy and 26 (31.3%) with a cervical intraepithelial lesion without invasion. Thirty‐eight (45.8%) had conditions of the cervix as follows: 12 cases had invasive disease of the cervix; nine (10.8%) adenocarcinoma of cervix and three (3.6%) squamous carcinoma of cervix. Nineteen (22.9%) had cervical intraepithelial neoplasia (CIN/SIL) alone and seven (8.4%) had cervical glandular intraepithelial neoplasia (CGIN) ± CIN. There were 16 (19.3%) cases with malignancies of the uterine corpus and six (7.2%) had a malignancy arising from another primary site. Twenty‐three (27.7%) had no malignant or pre‐malignant condition. The risk of malignancy was related to age and ranged from 18.2% in those under 35 years to 67.9% in those 55 years and over. A protocol for the management of these cases is described.
Abnormal chromosome 8 copy number in cytological smears from breast carcinomas detected by means of fluorescence in situ hybridization (FISH)
Authors: Bofin A. M. , Ytterhus B. , Fjøsne H. E. , Hagmar B. M.
Published: December 2004

Numerical change in chromosome 8 is an acquired abnormality associated with high clinical stage and may be involved in the conversion of carcinoma in situ in the breast to invasive carcinoma. Fine needle aspiration smears from 53 cases of breast carcinoma were hybridized with centromeric probes for chromosome 8 and the X chromosome. Thirty‐eight cases revealed chromosome 8 copy gain. Of the 45 grade II and III tumours, 28 showed polysomy (>3 signals) and six showed trisomy. Of the eight grade I tumours, four were trisomic, none were polysomic. There were only two cases of chromosome 8 copy loss (one each of grade I and III). X chromosome polysomy was also a frequent finding although the signal counts were similar to those for chromosome 8 in only a few cases. Chromosome 8 polysomy occurs frequently in breast carcinoma and high copy number (>3) is associated with high malignancy grade.
Ontogenetic change of prey preference in the generalist predator Zelus renardii and its influence on predator–predator interactions
Authors: CISNEROS JORGE , ROSENHEIM JAY
Published: December 2004

1. Two field experiments were conducted to test the hypothesis that the intensity of predation by a generalist predator on two species of prey changes with the developmental stage of the predator. The generalist predator studied was Zelus renardii Kolenati (Hemiptera: Reduviidae) and the prey were the lacewing larva, Chrysoperla carnea Stephens, and the cotton aphid, Aphis gossypii Glover.

2. Zelus renardii and lacewings feed on aphids, thereby acting as potential competitors. In addition, Z. renardii feeds on lacewings. Thus, Z. renardii is an intraguild predator of lacewings.

3. Zelus renardii exhibited changes in prey preferences across developmental stages. The older stages of Z. renardii exerted greater mortality on lacewings and fed on larger lacewing larvae than did the younger stages.

4. Lacewings suppressed aphid population growth strongly. In contrast, none of the stages of Z. renardii was an effective control agent of the cotton aphid.

5. The addition of Z. renardii frequently disrupted the effective control of aphids generated by lacewings. In one of the two replicates of the experiment, the disruption increased with the developmental stage of Z. renardii, paralleling the increase in lacewing mortality.

6. Although the developmental stage of Z. renardii can influence the prevalence of intraguild predation and the intensity of the disruption of the aphid biological control, these experiments have demonstrated that even the youngest instars of Z. renardii can cause substantial lacewing mortality and release aphid populations from regulation.