bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombination pattern of the TCR γ locus in human peripheral T‐cell lymphomas
Authors: Theodorou Joannis , Raphaël Martine , Bigorgne Claude , Fourcade Christine , Lahet Chantal , Cochet Gilles , Lefranc Marie‐Paule , Gaulard Philippe , Farcet Jean‐Pierre
Published: June 2005

The recombination events of the γ and β T‐cell receptor (TCR) loci were analysed in a series of 39 peripheral T‐cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR αβ PTCLs, 22/23 cases showed a γ‐gene rearrangement while only 18/23 showed a concomitant β‐gene rearrangement. The germline configuration of the β locus was found in angioimmunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three γδ PTCLs rearranged both γ and β genes. TCR silent PTCLs showed three different patterns of γ‐ and β‐gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged γ and a germline β locus; and five cases had the two loci rearranged. Regarding the variable genes in the γ‐rearranged alleles, members of the VγI subgroup were the most frequently presented (39/50), followed by VγII, VγIII, and VγIV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the γ locus is more frequently rearranged whatever the TCR expression. The γ‐locus analysis provides a better diagnostic yield than the β locus in the study of PTCL clonality.
The expression pattern of contractile and intermediate filament proteins in developing skeletal muscle and rhabdomyosarcoma of childhood: Diagnostic and prognostic utility
Authors: Wijnaendts Liliane C. D. , Van Der Linden Johannes C. , Van Unnik Adriaan J. M. , Delemarre Jan F. M. , Voute Paul A. , Meijer Chris J. L. M.
Published: June 2005

In order to investigate whether rhabdomyosarcoma (RMS) can be related to equivalent stages of skeletal muscle development, muscle tissue of 21 human foetuses and 112 primary RMSs were characterized immunohistochemically using antibodies directed against vimentin, desmin, muscle‐specific actin (HHF35), sarcomeric actin (sr‐actin), smooth muscle actin (sm‐actin), and troponin‐T. During fetal skeletal muscle development, all myotubes/fibres of the first and second generations expressed desmin, HHF35, and sr‐actin. Vimentin was almost exclusively present in immature primary and secondary myotubes/fibres. Troponin‐T was expressed in immature myotubes/fibres of the first and second generations as well as mature fibres of the second generation. Sm‐actin was never expressed. Vimentin was expressed in 96 per cent of primary and 98 per cent of relapsed RMS; HHF35 in 96 and 98 per cent, respectively; desmin in 95 and 100 per cent; troponin‐T in 82 and 75 per cent; sr‐actin in 71 and 86 per cent; and sm‐actin in 13 and 17 per cent. The proportion of RMS cells reacting with vimentin, HHF35, and desmin was consistently higher than those expressing sr‐actin and troponin‐T. Neither the shape nor size of neoplastic RMS cells nor the histopathological types were related to the expression pattern of the investigated markers. RMS with aberrant expression of two or more markers predicted a worse prognosis than RMS in which at most one marker was aberrantly expressed (25 per cent and 54 per cent 10‐year survival, P=0·01). These results demonstrate that HHF35, desmin, sr‐actin, and troponin‐T have the potential to confirm the commitment of the tumours to the myogenic pathway which supports the diagnosis of RMS. However, it was impossible to relate RMS to equivalent stages of skeletal muscle development. Aberrant marker expression by RMS cells correlated significantly with patients' survival.
Expression of mdr1/P‐glycoprotein and p110 in neuroblastoma
Authors: Ramani Pramila , Dewchand Hamlata
Published: June 2005

Overexpression of the multidrug resistance gene, mdr1, and its product, P‐glycoprotein (Pgp), has been associated with cross‐resistance to structurally unrelated compounds in cell lines and tumours. Recently, a non‐Pgp‐mediated form of drug resistance has been described, due to the overexpression of p110, a transport protein. Thirty formalin‐fixed, paraffin‐embedded neuroblastoma samples from 21 cases were examined for overexpression of mdr1 and Pgp using newly established non‐radioactive in situ hybridization and sensitive immunocytochemical techniques. Tumours were examined from patients with all the stages of disease and from primary and metastatic sites. Paired tumour samples (pre‐chemotherapy and post‐chemotherapy) were available from cases with stage 2 (n=1) and stage 4 disease (n=8). Immunoreactivity to p110 was also tested on all the samples. Mdr1 mRNA was expressed in 16/21 cases and in all the stages. Pgp immunoreactivity was detected in all the cases. Weak cytoplasmic immunoreactivity to p110 was seen in the ganglion cells in 12/21 cases. The expression of mdr1, Pgp, and p110 showed a statistically significant (two‐sided Fisher exact test, P=0.04, 0.03, 0.04, respectively) correlation with differentiation (Beckwith and Martin grading) but there was no correlation with survival. Pgp immunoreactivity also showed a significant correlation with favourable clinical variables: age less than 1 year at diagnosis and stages 1, 2, and 4 s (two‐sided Fisher exact test, P=0.01, 0.05, respectively).
Disruption of cell adhesion in renal epithelium without cadherin loss
Authors: O'Donnell Marie , Fleming Stewart
Published: June 2005

Loss of cell adhesion is a critical event in the development of tumour invasiveness and metastases. Although loss of cadherin expression has been demonstrated to be associated with increased invasiveness and metastatic potential in some tumours, others, including renal carcinoma, show no such correlation. The aim of this study was to demonstrate that cell adhesion could be lost in phorbol ester‐treated renal epithelial cells and renal tumour cells without loss of A‐CAM expression. The model used has been shown previously to mimic changes that occur in the progression of renal carcinoma. We found that A‐CAM expression persists on the lateral surfaces of phorbol ester‐treated cells even though these cells lose cell‐cell adhesion. Similar findings were seen in renal carcinoma cells in culture. We conclude that loss of cell adhesion between tumour cells may occur either by loss of cadherins or as a result of loss cadherin function occurring as a consequence of cell transformation.
Components of the plasminogen activation system in uveal melanoma—a clinico‐pathological study
Authors: de Vries Teunis J. , Mooy Cornelia M. , van Balken Michael R. , Luyten Gregorius P. M. , Quax Paul H. A. , Verspaget Hein W. , Weidle Ulrich H. , Ruiter Dirk J. , van Muijen Goos N. P.
Published: June 2005

In tumour development, proteases such as plasminogen activators (PAs) play a role in degradation of the extracellular matrix and other tissue barriers. Recently, we demonstrated that plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of cutaneous melanocytic tumour progression. In this study we investigated the expression and distribution of the various components of the PA system and the presence of PA enzyme activity in 45 freshly frozen primary uveal melanomas with known follow‐up (14 spindle and 31 non‐spindle type) and in metastases (n=5). Tissue‐type PA (t‐PA) was found in endothelium of blood vessels and in tumour cells in almost all leisons, and was markedly present at the invasive front (towards the sclera and Bruch's membrane), but no correlation with tumour‐related death could be established. Urokinase PA (u‐PA) was expressed focally, by only five non‐spindle cell melanomas but in all metastases. u‐PA expression correlated with occurence of metastasis. u‐PA receptor (u‐PAR) was present in one‐third of all the tumours examined. Plasminogen activator inhibitors (PAI‐1 and PAI‐2) were found only focally in approximately 10 per cent of the lesions. Staining of t‐PA, u‐PA, and PAI was observed in all the metastases. We conclude that in uveal melanoma, u‐PA expression may be associated with metastatic disease and accordingly with a poor prognosis. Further research on a larger group of tumours with known follow‐up is needed to establish whether u‐PA positivity is of additional prognostic value in uveal melanoma.
Detection of numerical chromosomal aberrations in paraffin‐embedded malignant pleural mesothelioma by non‐isotopic in situ hybridization
Authors: Segers Kurt , Ramael Marc , Singh Samir Kumar , van Daele André , Weyler Joost , van Marck Eric
Published: June 2005

An in situ hybridization (ISH) study on paraffin sections of 13 malignant mesotheliomas was performed to detect numerical chromosomal aberrations with biotin‐labelled DNA probes specific for the centromeric regions of chromosomes 1, 3, 6, 7, 11, and 17. All chromosomes contributed to numerical changes, which can be summarized as follows: first, a monosomy for chromosome 6 was found in one case; second, in five cases a trisomy for at least one chromosome was detected; and third, in seven cases a pentasomy or a higher polysomy was found for at least one chromosome. Although these data have to be confirmed on a larger group of patients, survival analysis of this group showed no significant difference between the first and second groups taken together and the third group. In this study no specific numerical chromosomal aberrations were identified. Nevertheless, numerical gains appear to be more frequent than has previously been shown by karyotype analysis.
Expression of parathyroid hormone‐related peptide in human thyroid tumours
Authors: Nakashima Masahiro , Ohtsuru Akira , Luo Wen Tian , Nakayama Toshiyuki , Enomoto Hiroshi , Usa Toshiro , Kiriyama Takeshi , Ito Masahiro , Nagataki Shigenobu , Yamashita Shunichi , Sekine Ichiro
Published: June 2005

The purpose of this study was to evaluate the distribution of parathyroid hormone‐related peptide (PTHrP) in human thyroid tissues. The presence of PTHrP was studied immunohistochemically in 107 consecutive patients with human thyroid tumours. PTHrP expression was revealed in 97.6 per cent of carcinomas, but not in paranodal normal thyroid epithelial cells. Although there were no differences in the incidence of PTHrP positivity among papillary, follicular, and anaplastic carcinoma cases, PTHrP expression levels were correlated with the growth pattern of thyroid cancer. Strong immunopositivity was detected in 67.3 per cent of papillary growth tissues in papillary carcinomas. A tissue growth pattern consisting of colloid‐absent follicles had a high incidence of strong immunopositivity irrespective of the histological type of tumour. Anaplastic carcinoma without colloid production also showed strong immunoreactivity in all cases. In contrast, a growth pattern of colloid‐rich follicles did not show strong immunopositivity in either papillary or follicular carcinomas. Follicular adenomas showed positive immunostaining in only one case, and no adenomatous goitres showed PTHrP antigens. In situ hybridization and reverse transcription‐polymerase chain reaction (RT‐PCR) revealed strong PTHrP mRNA in thyroid cancer tissues, but not in normal thyroid tissues. PTHrP expression was not associated with metastasis, calcification, or hypercalcaemia in thyroid cancers. These results suggest that the expression of PTHrP in human thyroids is closely related to the malignant alteration of normal thyroid epithelial cells, especially in the growth pattern of thyroid carcinoma tissues.
Absence of overexpression of p53 protein by intestinal carcinoid tumours
Authors: O'dowd G. , Gosney J. R.
Published: June 2005

A recessive gene on chromosome 17 encodes a protein, known as p53, which normally acts to regulate the cell cycle, its mutation and overexpression being amongst the commonest genetic abnormalities in human malignant neoplasms. As detected by immunolabelling using the anti‐p53 protein antibody D07, overexpression was absent from a series of 22 intestinal carcinoid tumours (ten ileal, nine appendiceal, and three colorectal), nine overtly malignant, but was readily demonstrable in five of five colorectal adenocarcinomas, five of six cloacogenic carcinomas, and four of five squamous carcinomas of the anal canal used as controls. These observations are in keeping with previous similar studies of pulmonary carcinoid tumours and suggest possible differences in the pathogenesis of such neoplasms in comparison with non‐endocrine differentiated tumours arising at equivalent sites.
Ultrastructural detection of DNA strand breaks in apoptotic neural cells by in situ end‐labelling techniques
Authors: Migheli Antonio , Attanasio Angelo , Schiffer Davide
Published: June 2005

Recently developed techniques based on ‘in situ end‐labelling’ (ISEL) of DNA strand breaks may help to identify apoptotic cells in tissue sections. We have applied ISEL techniques at the electron microscopic (EM) level, in order to verify if ultrastructural features of apoptosis are indeed associated with evidence of DNA fragmentation, and whether cells committed to, but which have not yet entered the stage of cell death are also labelled. Terminal transferase and DNA polymerase assays were applied to thin sections of Araldite and LR Gold‐embedded medulloblastomas and embryonic mouse dorsal root ganglia. Digoxigenin‐labelled nucleotides were used; incorporation was demonstrated by immunogold staining. Apoptotic cells in various stages of the death process were easily labelled in both tissues. In addition, DNA fragmentation was demonstrated in cells with initial chromatin condensation, but otherwise indistinguishable from adjacent unstained cells. Our results show that EM‐ISEL techniques effectively demonstrate the occurrence of DNA strand breaks in apoptotic and possibly ‘pre‐apoptotic’ cells in neural tissues. Since the labelling is easily obtained on tissue that is routinely processed for electron microscopy, this technique may allow retrospective studies on archival material.
Regulation of murine germinal centre cell proliferation in vivo: A stathmokinetic study examining the effect of differently timed doses of cyclosporin A
Authors: Goodlad John R. , Macartney James C.
Published: June 2005

Although studies have identified factors which affect germinal centre cell proliferation in vitro, their relative contributions in vivo remain largely undetermined. In this study, the proliferative rate of germinal centre cells was measured in sheep red blood cell‐immunized C3H/HeN mice exposed to variously timed doses of cyclosporin A. Germinal centre (GC) cell proliferation was measured by a stathmokinetic technique to determine GC cell birth rates at specific time points after immunization. Changes in total GC volume were determined by morphometry in order to assess actual growth and regression of the GC cell population. An estimate of the absolute rate of GC cell proliferation was derived from these two values. Following exposure to antigen, there was an initial inhibition of proliferation within pre‐existing germinal centres, followed by a rapid rise, then a sustained phase of increased GC cell proliferation. By comparing the effects of the different cyclosporin A treatment regimes, it was possible to deduce that the initial inhibition of proliferation was mediated by a T‐cell‐derived cytokine, as was the final sustained phase of the proliferative response. The intervening rise in GC cell proliferation, however, was attributable to a contact‐dependent signalling mechanism.
Parathyroid hormone‐related protein antigen localization distinguishes between mesothelioma and adenocarcinoma of the lung
Authors: Clark Simon P. , Chou S. T. , Martin T. John , Danks Janine A.
Published: June 2005

The distinction between pleural malignant mesothelioma and pulmonary adenocarcinoma remains a problem in diagnostic histopathology. Parathyroid hormone‐related protein (PTHrP) has been demonstrated in the neoplastic cells of malignant mesotheliomata, using a polyclonal antiserum raised to synthetic PTHrP(1–16). In a series of 44 malignant mesotheliomata and 44 cases of pleural adenocarcinomata, PTHrP was localized immunohistochemically in 84 per cent of the mesotheliomata and in 11 per cent of the pleural adenocarcinomata. Normal and reactive mesothelium did not contain detectable PTHrP. The presence of PTHrP in a very high percentage of malignant mesotheliomata indicates the value of including it in the panel of antibodies utilized in the differential diagnosis of mesothelioma.
Microwave antigen retrieval for immunocytochemistry on formalin‐fixed, paraffin‐embedded post‐mortem CNS tissue
Authors: McQuaid Stephen , McConnell Robert , McMahon Jill , Herron Brian
Published: June 2005

Microwave antigen retrieval methods were assessed for a panel of antibodies on formalin‐fixed, paraffin‐embedded sections from a range of human central nervous system (CNS) tissues taken at post‐mortem. The immunoreactivity of a number of antigens (synaptophysin, PGP9.5, GFAP, carbonic anhydrase II, CD68, ferritin, HLA‐DR, αβ‐crystallin, mealses and herpes viruses) was markedly enhanced by this procedure compared with other methods of antigen unmasking, such as trypsinization. Enhancement was noted both by an increased number of positive cells and by the intensity of reactions within individual cells and their processes. Furthermore, the microwave method produced uniform immunostaining over large surface area sections with no loss of morphological detail. Large cryostat sections of CNS tissue can be difficult to obtain with good morphology. The ability to retrieve a wide range of antigen in formalin‐fixed, paraffin‐embedded CNS tissue will greatly increase the range of investigations that can be carried out on this type of stored material.
Expression of integrin subunits in the human infant breast correlates with morphogenesis and differentiation
Authors: Anbazhagan Ramaswamy , Bartek Jarina , Stamp Gordan , Pignatelli Massimo , Gusterson Barry
Published: June 2005

Integrins are widely expressed on normal tissues and their function is considered critical directly or indirectly with the control of cell growth and differentiation. Also, they are likely to play a crucial role in cell–matrix interactions during development. As the human breast develops after birth, it provides a rare opportunity in which to study human organogenesis. We have examined the distribution of integrins in the human infant breast with the aim of elucidating the possible role of these molecules in morphogenesis and differentiation. Necropsy breast specimens from six male and eight female infants, ranging in age from 1 day to 9 months, were used in this study. Cryostat sections were stained by the avidin‐biotin complex technique, using a panel of monoclonal antibodies (MAbs) which recognize β1, α2, α6, β4, αv, and αvβ3 integrin chains, which are candidate molecules for a role in mammory morphogenesis. MAbs to β1 (DH12) and α2 (HAS3) showed positive membrane and cytoplasmic staining of basal cells and luminal epithelial cells. In addition, positive staining for the β1 integrin chain was found on fibroblasts. A MAb which recognizes the α6 chain (MP4F10) showed positive staining of the basal cells and heterogeneous staining of the luminal epithelial cells, whilst β4 chain (439‐9B) showed positive staining in the basement membrane domain of the basal cells with no staining of the luminal epithelial cells. There was a positive correlation between the intensity of expression and the structural development of the ductal system, with integrin expression reduced or absent in the end buds and lateral buds. These data provide evidence that some integrin molecules are expressed in a pattern that correlates with the morphological and functional differentiation of the normal mammary gland. Changes in the expression and function of integrins may have an inductive role in the development of the normal mammary gland.
The sequential accumulation of genetic alterations characteristic of the colorectal adenoma–carcinoma sequence does not occur between gastric adenoma and adenocarcinoma
Authors: Maesawa Chihaya , Tamura Gen , Suzuki Yasushi , Ogasawara Satoshi , Sakata Ken , Kashiwaba Masahiro , Satodate Ryoichi
Published: June 2005

We screened 30 gastric adenomas and 72 gastric adenocarcinomas for four genetic alterations (mutations of the K‐ras, APC, and p53 genes and loss of heterozygosity at the DCC genetic locus) which are known to occur during colorectal tumourigenesis. We used polymerase chain reaction (PCR) single‐strand conformation polymorphism analysis to detect mutations. Loss of heterozygosity (LOH) at the DCC locus was ascertained directly by performing PCR on the variable number of tandem repeats within the gene. Mutations of the K‐ras gene were not detected in any gastric adenoma or carcinoma. APC mutations were detected in 20 per cent (6/30) of the adenomas but in only 1·4 per cent (1/72) of the carcinomas. In contrast, the p53 gene was frequently mutated in carcinomas (35 per cent; 25/72), but not in adenomas. LOH at the DCC locus was a frequent occurrence in carcinomas (58 per cent; 11/19 informative cases) but was infrequent in adenomas (14 per cent; 1/7). Alterations of the p53 and DCC genes occurred frequently both in differentiated and in undifferentiated gastric carcinomas. The considerable differences in the incidences of genetic alerations between gastric adenoma and carcinoma indicate that the sequential development of gastric carcinoma from adenoma is uncommon in gastric carcinogenesis.
Ductal carcinoma in situ: Assessment of necrosis and nuclear morphology and their association with biological markers
Authors: Bobrow Lynda G. , Happerfield Lisa C. , Gregory Walter M. , Millis Rosemary R.
Published: June 2005

One hundred and five cases of pure ductal carcinoma in situ (DCIS) seen in the Guy's Hospital breast unit between 1975 and 1991 were reviewed. The presence and extent of necrosis and the degree of cytonuclear differentiation were assessed and the expression of p53 protein, cerbB2 protein, progesterone receptor, and a proliferation antigen KiS1, all factors reported to be of prognostic significance in invasive ductal carcinoma, was evaluated using immunohis‐tochemical methods. A strong correlation was seen between the presence and extent of necrosis and the degree of cytonuclear differentiation and between both these morphological criteria and the biological markers as well as between the individual markers. The presence of extensive necrosis was associated with lack of cytonuclear differentiation and both were associated with a high proliferation rate, the presence of cerbB2 and p53 protein, and the absence of progesterone receptors. In cases with little or no necrosis, there was good nuclear differentiation and a strong correlation with the presence of progesterone receptor, absence of cerbB2 and p53 protein, and a low rate of proliferation.
Detection of Herpes simplex virus DNA in spontaneous abortions from HIV‐positive women using non‐isotopic in situ hybridization
Authors: Wright Collen A. , Haffajee Zenobia , Van Iddekinge Basil , Cooper Kum
Published: June 2005

The purpose of this study was to determine the prevalence of Herpes simplex virus (HSV) endometritis in spontaneous abortions in HIV‐positive women using non‐isotopic in situ hybridization (NISH). Post‐abortal endometrial curettings from 18 HIV‐positive women were investigated for the presence of HSV‐1 and HSV‐2 DNA with NISH. In addition, 18 unselected post‐abortal endometrial curettings in HIV‐negative women were used as controls, together with samples of normal proliferative and secretory endometrium. Thirteen of the 18 specimens (72 per cent) from the HIV‐positive study group demonstrated the presence of HSV DNA, while 2 of the 18 HIV‐negative group (11 per cent) showed a positive signal. Although the prevalence of HSV endometritis in the HIV‐positive group was significantly higher than in the HIV‐negative group (P<0.05), a causal role for the virus in inducing the abortion remains to be determined. In addition, the significance of HSV endometritis with regard to the clinical management of HIV‐positive patients is as yet uncertain.
Unusual retention of introns in CD44 gene transcripts in bladder cancer provides new diagnostic and clinical oncological opportunities
Authors: Matsumura Yasuhiro , Sugiyama Makoto , Matsumura Shoko , Hayle Allan J. , Robinson Philip , Smith Joseph C. , Tarin David
Published: June 2005

Increased and disorganised expression of CD44 variant exons has been demonstrated in biopsy samples of several types of human malignancy by many groups. This abnormality can be used to detect exfoliated tumour cells in the urine of bladder cancer patients. The present report demonstrates that the deranged activity of this gene in neoplasia also results in the accumulation of immature mRNA transcripts containing non‐coding sequences (introns) from this gene in cancer tissues and cells. There is simultaneous overexpression of a newly identified 437 bp exon (coding sequence) located in the variably active region of the gene and of many abnormal variant exon combinations. This is the first report describing the specific retention of introns in gene transcripts in clinical diagnotic samples of tumour tissues and cells. The phenomenon was seen repeatedly in samples from cancer patients and in a cancer cell line, and thus could form the basis for a unique new and specific method of cancer diagnosis.
High frequency of light chain restriction in labial gland biopsies of Sjögren's syndrome detected by in situ hybridization
Authors: Jordan Richard C. K. , Pringle J. H. , Speight Paul M.
Published: June 2005

A well‐recognized complication of Sjögren's syndrome (SS) is the development of malignant lymphoma, with a risk 44 times that of the general population. Although a few clinical signs may indicate the onset of lymphoma, there are few reliable laboratory markers which predict the development of neoplasia. A non‐isotopic in situ hybridization technique has been applied to routinely processed labial salivary gland (LSG) biopsies of patients under investigation for SS. Serial sections of 70 LSGs were examined for a κ and λ immunoglobulin light chain mRNA using digoxigenin‐labelled oligonucleotide probes. As controls, 39 biopsies from non‐SS‐associated sialadenitis were also examined. Sections were analysed using computer‐assisted quantification to determine the percentage of κ‐expressing cells in each case. The range of κ expression in the SS group was 24·1–93·4 per cent and in the non‐SS group 48·3–75·4 per cent. Light chain restriction was found in 13/70 (18·6 per cent) cases from the SS group but in no cases of the control group. Of the SS cases showing restriction, 4/13 (30·7 per cent) have subsequently developed extrasalivary gland lymphoma. Two patients not showing light chain restriction in LSG have subsequently developed lymphoma. The positive predictive value of this test to identify patients at risk of lymphoma was 30·7 per cent with a detection rate (sensitivity) of 66·47 per cent and a false‐positive rate of 14·1 per cent (specificity 85·9 per cent). This study has identified a high prevalence of light chain restriction in labial gland biopsies of patients with SS and provides objective quantitative criteria to identify those patients at greater risk of lymphoma development.
Expression of the c‐kit gene product in normal and neoplastic mast cells but not in neoplastic basophil/mast cell precursors from chronic myelogenous leukaemia
Authors: Fukuda Takeaki , Kamishima Tomoko , Tsuura Yukio , Suzuki Toshimitsu , Kakihara Toshio , Naito Makoto , Kishi Kenji , Matsumoto Kazuhito , Shibata Akira , Seito Tsutomu
Published: June 2005

The expression of the c‐kit gene product has been examined in normal mast cells, mast cell neoplasms, and basophil/mast cell precursors obtained from patients with chronic myelogenous leukaemia (CML). Formalin‐fixed, paraffin‐embedded sections or smears fixed with formalin vapour were studied by immunohistochemical methods, using a polyclonal antibody against the c‐kit gene product. Normal and neoplastic mast cells showed a positive immunoreaction for c‐kit gene product, but neoplastic basophil/mast cell precursors from CML patients lacked c‐kit gene product by immunohistochemical and flow cytometric methods, even in cells having mast cell granules, together with or without basophil granules. Mast cell tryptase was, however, expressed in normal and neoplastic mast cells and basophil/mast cell precursors containing mast cell granules. In addition, cells of monocyte/macrophage lineage lacked c‐kit gene product. These findings indicate that the c‐kit gene product may play an important role in the development and function of mast cell but not of cell of basophil and monocyte/macrophage lineage.
Immunohistochemical localization of ubiquitin cross‐reactive protein in human tissues
Authors: Lowe James , McDermott Helen , Loeb Keith , Landon Michael , Haas Arthur L. , Mayer R. John
Published: June 2005

Ubiquitin cross‐reactive protein (UCRP) is an interferon‐inducible ubiquitin homologue which is constitutively present in cells and can be conjugated to other proteins. Using a characterized polyclonal antiserum to UCRP, immunohistochemical localization of UCRP was performed on paraffin‐processed normal human tissues and in human tissues known to contain ubiquitinated intracellular inclusions. The antibody to UCRP immunostained lymphoid cells, striated and smooth muscle, several epithelia, and neurons. The level of staining varied greatly between tissues but was in a consistent punctate pattern. Localization to neuromuscular junctions and striations is similar to that described for antisera to ubiquitin‐protein conjugates. Inclusion bodies characterized by immunoreactivity to anti‐ubiquitin were not detected by the antibody to UCRP. Importantly, because UCRP may also be detected by antisera to conjugated ubiquitin, future studies on the distribution of ubiquitin in tissue sections must now take account of possible cross‐reactivity with UCRP.
Vascular networks within the stroma of human long‐term bone marrow cultures
Authors: Wilkins Bridget S. , Jones David B.
Published: June 2005

The formation of branching and anastomosing vascular structures has been demonstrated within the stromal layers of human long‐term bone marrow cultures (LTBMCs). Such organized vascular structures have not been described previously and may be of functional importance, as adherent granulocyte‐predominant haemopoietic foci were more numerous in their interstices and margins than elsewhere in the stromal layers. Mature granulocytes were seen within vascular lumina in a few instances, possibly indicating an attempt to recapitulate the normal process of egress of neutrophils from bone marrow into the circulation. Immunostaining showed that the vascular structures expressed CD31, CD34, and CD105 (endoglin), which were not expressed by stromal fibroblastic cells. Collagen IV and laminin, expressed throughout the stroma, were present in increased amounts where vascular arrays were seen. In contrast, von Willebrand factor (VWF) and vascular cell adhesion molecule‐1 (VCAM‐1) were expressed equally by the vascular arrays and by stromal fibroblastic cells. Neither the arrays nor the general stroma expressed intercellular adhesion molecule‐1 (ICAM‐1), ICAM‐2, ICAM‐3, or endothelial leukocyte adhesion molecule‐1 (ELAM‐1).
Personality and personality disorders: introduction to the special issue
Authors: Ostendorf Fritz , Riemann Rainer
Published: June 2005

The study of extreme variants of phenomena has always been a challenge for science. While the science of personality has roots in several traditions, historically numerous personality theories and constructs for the assessment and explanation of individual differences have strongly been influenced by the progress made in conceptualizing extreme states of psychological functioning. Yet, division of labour resulted in psychiatry and clinical psychology focusing on deviant or maladaptive and personality psychology specializing on the normal range of individual differences. This special issue of the European Journal of Personality is driven by the idea that linking the study of personality and psychopathology offers insights that neither discipline can achieve on its own. Copyright © 2005 John Wiley & Sons, Ltd.
Psychosocial adversity and emotional instability: an application of gene–environment interaction models
Authors: Jang Kerry L. , Dick Danielle M. , Wolf Heike , Livesley W. John , Paris< Joel
Published: June 2005

A central idea in personality theory is that events in childhood have an effect on the development of personality. The present study applied models of gene–environment interaction that demonstrate how environmental conditions may moderate genetic variability in a population and/or the influence of other environmental effects. Results showed that perceived levels of family conflict and maternal indulgence moderated the genetic influences underlying emotional instability, a central feature of borderline personality disorder. The analyses identified a wide variety of environmental influences that moderate the variability in the liability to emotional instability, such as perceived levels of parental bonding, family functioning, and exposure to nonassaultive traumatic events. Copyright © 2005 John Wiley & Sons, Ltd.
DSM‐IV personality disorders and the Five‐Factor Model of personality: a multi‐method examination of domain‐ and facet‐level predictions
Authors: Bagby R. Michael , Costa Paul T. , Widiger Thomas A. , Ryder Andrew G. , Marshall Margarita
Published: June 2005

The personality disorder classification system (Axis II) in the various versions of the Diagnostic and Statistical Manuals of Mental Disorders (DSM) has been the target of repeated criticism, with conceptual analysis and empirical evidence documenting its flaws. In response, many have proposed alternative approaches for the assessment of personality psychopathology, including the application of the Five‐Factor Model of personality (FFM). Many remain sceptical, however, as to whether domain and facet traits from a model of general personality functioning can be successfully applied to clinical patients with personality disorders (PDs). In this study, with a sample of psychiatric patients (n = 115), personality disorder symptoms corresponding to each of the 10 PDs were successfully predicted by the facet and domain traits of the FFM, as measured by a semi‐structured interview, the Structured Interview for the Five Factor Model (SIFFM; Trull & Widiger, 1997) and a self‐report questionnaire, the Revised NEO Personality Inventory (NEO PI‐R; Costa and McCrae, 1992). These results provide support for the perspective that personality psychopathology can be captured by general personality dimensions. The FFM has the potential to provide a valid and scientifically sound framework from which to assess personality psychopathology, in a way that covers most of the domains conceptualized in DSM while transcending the limitations of the current categorical approach to these disorders. Copyright © 2005 John Wiley & Sons, Ltd.
Study of the effect of poly(vinyl alcohol) concentration on the gelation point of poly(vinyl alcohol) poly(acrylic acid) semi‐IPN systems as determined by viscoelastic measurements
Authors: Hernández Rebeca , Mijangos Carmen , López Daniel
Published: June 2005

We report on the determination of the gelation point of semi‐interpenetrating polymer networks (semi‐IPNs) composed of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAAc) formed by a sequential method. The evolution of the viscoelasticity during the gelation reaction of acrylic acid (AAc) in solutions of PVA has been monitored through the sol‐gel transition with dynamic mechanical experiments. The gelation time of the system increased with PVA concentration; however, the molecular structure of the gel, composed of swollen clusters, is rather independent of the presence of PVA. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1944–1949, 2005
Dissection of the functional domains of the sarcoplasmic reticulum Ca2+-ATPase by site-directed mutagenesis
Authors: Andersen Jens Peter
Published: June 2005

The results of site-directed mutagenesis studies of the sarcoplasmic reticulum Ca2+-ATPase are reviewed. More than 250 different point mutants have been expressed in cell culture and analysed by a panel of functional assays. Thereby, 40–50 important amino acid residues have been pinpointed, and the mutants have been assigned to functional classes: the Ca2+-affinity mutants, the phosphorylation-negative mutants, the ATP-affinity mutants, the E1P mutants, the E2P mutants, and the uncoupled mutants. Moreover, regions important to the specific inhibition by thapsigargin have been identified by analysis of Ca2+-ATPase/Na+, K+-ATPase chimeric constructs.
The mechanism of coupling chemical and physical reactions by the calcium ATPase of sarcoplasmic reticulum and other coupled vectorial systems
Authors: Jencks William P.
Published: June 2005

The coupling of the chemical reaction of ATP hydrolysis to the transport of calcium from the cytoplasm into the lumen of sarcoplasmic reticulum vesicles can be defined by a set of rules that define alternating changes in the specificities of the enzyme for catalysis of chemical and physical reactions.
How do Ca2+ ions pass through the sarcoplasmic reticulum membrane
Authors: Mintz Elisabeth , Guillain Florent
Published: June 2005

We propose an overview of the mechanism of Ca2+ transport through the sarcoplasmic reticulum membrane via the Ca2+-ATPase. We describe cytoplasmic calcium binding, calcium occlusion in the membrane and lumenal calcium dissociation. A channel-like structure is discussed and related to structural data on the membranous domain of the Ca2+-ATPase.
Methadone treatment of chronic non‐malignant pain and opioid dependence — A long‐term follow‐up
Authors: Rhodin A. , Grönbladh L. , Nilsson L.‐H. , Gordh T.
Published: June 2005

Iatrogenic opioid addiction among chronic pain patients was the initiative for starting a methadone programme for pain patients at the University Hospital of Uppsala. The aims were to improve pain relief and quality of life in pain patients with problematic opioid use and to investigate background factors explaining problems with opioid use.

Methods Records of all 60 patients included in the methadone programme 1994–2002 were studied. An interview was done after a mean of 34 months of methadone treatment regarding pain relief, quality of life and side effects on 48 patients.

Results Titration of oral methadone mixture in daily doses ranging from 10 to 350 mg (mean 99.5 mg) was done on all patients. Background factors were low back and musculoskeletal pain in 40%, psychiatric disease in 68%, and substance use disorder in 32% of the patients. Before methadone treatment all patients were on sick leave. After treatment five patients returned to work. Ten patients failed treatment, 4 due to intractable nausea, 4 to drug diversion, 1 because of methadone related arrhythmia and 1 because of insufficient analgesia. Pain relief was rated good by 75% and moderate by 25% of the patients. Global quality of life was rated at mean of 50(0‐100), which favourably compares with Swedish chronic pain patients mean 33(0‐100).

Conclusion A structured methadone programme can be used for treating chronic pain patients with opioid dependence improving pain relief and quality of life. However, side effects and serious adverse events may limit the beneficial effects of the method.
A high incidence of intussusception in Japan as studied in a sentinel hospital over a 25-year period (1978–2002)
Authors: NAKAGOMI T. , TAKAHASHI Y. , ARISAWA K. , NAKAGOMI O.
Published: June 2005

The development of second-generation rotavirus vaccines requires knowledge of baseline incidence rates for intussusception in infants prior to vaccine introduction. To obtain such estimates we reviewed clinical records in a hospital that served as the major provider of paediatric beds in a local community in the northern part of Japan. During the 25-year period (1978–2002), there were 91 hospitalizations due to radiologically confirmed intussusception in children <5 years of age, of which 45% were <1 year of age. Assuming that all children with intussusception in the area had been admitted to this hospital, there were an average of 185 and 78 hospitalizations per 100 000 person-years for children <1 year old and 5 years old respectively. There was period-to-period variability with no long-term secular trend in the incidence of intussusception. The incidence rate in Japan was among the highest thus far reported, providing further evidence of geographic variability.
Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath
Authors: DUPREE JEFFREY L. , MASON JEFFREY L. , MARCUS JILL R. , STULL MICHAEL , LEVINSON ROCK , MATSUSHIMA GLENN K. , POPKO BRIAN
Published: June 2005

To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na+) channels accumulate in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na+ channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na+ channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance of nodal protein organization. Finally, we present evidence that following the loss of Na+ channel clusters the chronological progression of expression and reclustering of Na+ channel isoforms during the course of CNS remyelination recapitulates development.
Transplanted olfactory ensheathing cells modulate the inflammatory response in the injured spinal cord
Authors: LóPEZ-VALES RUBèN , GARCíA-ALíAS GUILLERMO , FORéS JOAQUIM , VELA JOSé M. , NAVARRO XAVIER , VERDú ENRIQUE
Published: June 2005

Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to exert neuroprotective effects and promote functional recovery. In the present study, we investigated the potential modulatory effects of OECs on the inflammatory reaction developed after photochemical injury to the spinal cord. OEC cultures were obtained from olfactory bulbs of adult Sprague-Dawley rats. Photochemical spinal cord injury was induced in adult rats at T8. Thirty minutes after the insult, either a suspension of OECs (180 000 cells in 12 µl DMEM) or DMEM alone was injected into the lesioned spinal cord. At 3, 7 and 14 days post-operation (dpo), five animals from each group were processed for histology. Double-fluorescent labeling of transverse sections of the cord were made by combination of immunohistochemistry for inflammatory markers, interleukin 1β (IL-1β) and inducible nitric oxide synthase (iNOS), and for selective markers of astrocytes (glial fibrillar acidic protein; GFAP) and microglia/macrophages (tomato lectin; LEC). Differences in the intensity and time course of glial response, and IL-1β and iNOS expression were found between the two groups of rats. The reactivity grade against IL-1β, iNOS, GFAP and LEC in OEC-transplanted rats was higher at 7 dpo and lower at 14 dpo compared with DMEM-injected rats. These results indicate that the mechanisms underlying neuroprotection by OECs might be caused by earlier, higher and shorter duration of microglia/macrophage and astrocyte responses after injury.
Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking at synapses
Authors: DU JING , QUIROZ JORGE , YUAN PEIXIONG , ZARATE CARLOS , MANJI HUSSEINI K.
Published: June 2005

There is increasing evidence that severe mood disorders are associated with impairment of structural plasticity and cellular resilience. Cumulative data demonstrate that mood stabilizers regulate intracellular signaling cascades, including protein kinase C (PKC), PKA, mitogen-activated protein (MAP) kinase, glycogen synthase kinase 3-β (GSK3-β) and intracellular calcium, which are signaling pathways that regulate synaptic plasticity. In this context, it is noteworthy that a growing body of data indicates that the glutamatergic system, has a major role in neuronal plasticity and cellular resilience, might be involved in the pathophysiology and treatment of mood disorders. AMPA glutamate-receptor trafficking is important in synaptic plasticity and might play crucial roles in maintaining critical neuronal circuits associated with mood. Two clinically effective, structurally dissimilar, antimanic agents, lithium and valproate (VPA), down-regulate synaptic expression of AMPA receptor subunit GluR1 in hippocampus in chronically treated rats. This reduction in synaptic GluR1 by lithium and VPA is due to attenuated phosphorylation of GluR1 at a specific PKA site (residue 845 of GluR1), which is crucial for AMPA receptor insertion. By contrast, imipramine, which can provoke mania, increases synaptic expression of GluR1 in the hippocampus in vivo. Furthermore, there is ample evidence from preclinical and clinical research that the glutamatergic system is involved in the pathophysiology of mood disorders and that many of the somatic treatments used for mood disorders including antidepressants, mood stabilizers, atypical antipsychotic drugs and electroconvulsive therapy have both direct and indirect effects on the glutamatergic system. Given these findings, further research with medications that specifically affect the glutamatergic system is warranted. Recent studies in our lab have shown that riluzole, a FDA approved medicine that regulates the glutamatergic system, shows antidepressant efficacy in unipolar and bipolar depression. These studies indicate that regulation of glutamate-mediated synaptic plasticity might play a role in the treatment of mood disorders, and raise new avenues for novel therapies for this devastating illness.
Analysis of trends in maximum and minimum temperature, diurnal temperature range, and cloud cover over India
Authors: Roy Shouraseni Sen , Balling Robert C.
Published: June 2005

We assembled data at a 1° latitude by 1° longitude resolution for 285 cells across India and analyzed the seasonal trends in the maximum and minimum temperature, diurnal temperature range (DTR), and cloud cover for the time period 1931–2002. Significant increases in maximum and minimum temperature have occurred over the Deccan plateau, but in general, trends in DTR were not significant except for a decrease in northwest Kashmir in summer. The effect of cloud cover on the DTR was expectedly negative for most of the country for winter and summer seasons with significant increase in summer cloud cover in Kashmir.