bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary gland disease in HIV/AIDS and primary Sjögren's Syndrome: analysis of collagen I distribution and histopathology in American and African patients
Authors: McArthur Carole P. , Africa Charlene W. J. , Castellani William J. , Luangjamekorn Nida J. , McLaughlin Matthew , Subtil‐DeOliveira Antonio , Cobb Charles , Howard Paul , Gustafson Steven , Palmer Dennis , Miranda Roberto N.
Published: September 2003

Background:  Salivary gland disease (SGD) in HIV/AIDS is clinically and histopathologically very similar to Sjögren's Syndrome (SS), although the mechanism of tissue damage is unknown. The aim of this study is to determine the prevalence of SGD in primary SS and in HIV/AIDS in USA and in West African patients, and to seek distinguishing histopathologic features that may help to elucidate underlying mechanisms.

Methods:  Histologic sections of minor salivary glands from 164 HIV‐positive and ‐negative patients from Cameroon and the US, and from 17 US patients with primary SS, were evaluated following salivary gland biopsy for inflammatory changes. To confirm the presence of fibrosis, collagen I, which is the most abundant collagen type, was assessed immunohistochemically in H&E‐stained sections.

Results:  Forty‐eight per cent of patients with HIV from Cameroon had severe SGD, while it was only in 6% of patients from the US. Patients with HIV in the US had less fibrosis and collagen I deposits than Cameroonians. Seventy‐six per cent of US HIV‐positive patients had received anti‐retroviral therapy, while none of the African patients had. SS and AIDS patients had a tendency for lymphocytes to locate in a perivascular rather than in a periductal distribution.

Conclusions:  The prevalence of SGD and the presence of fibrosis and collagen I in Cameroonians with HIV is significantly higher than in HIV‐positive American patients, and is similar to US patients with primary SS. The impact of patient selection, anti‐retroviral therapy, and pathogenic mechanisms on salivary gland pathology is discussed.
Exfoliative cytology of the oral mucosa in type II diabetic patients: morphology and cytomorphometry
Authors: Alberti Sandra , Spadella César T. , Francischone Telma R. C. G. , Assis Gerson F. , Cestari Tania M. , Taveira Luís A. A.
Published: September 2003

Background:  In recent years, important advances have occurred in the determination of diagnostic criteria for the disease diabetes mellitus and in new strategies for its treatment. The purpose of this research was to develop a new method for diabetes diagnosis by microscopic and cytomorphometric analyses of the oral epithelium.

Methods:  The smears were obtained from three distinct oral sites: buccal mucosa (cheek), tongue dorsum, and floor of the mouth in 10 control individuals and 10 type II diabetic patients. The oral smears were stained with Papanicolaou EA‐36 solution. The nuclear (NA) and cytoplasmic (CA) areas were evaluated from 50 integral cells predominant in each oral site by the use of the KS 300™ image analysis system (Carl Zeiss, Germany), by which the cytoplasmic/nuclear ratio (C/N) was calculated.

Results:  The results showed that: (i) the epithelial cells of the diabetic group exhibited figures of binucleation and occasional karyorrhexis in all layers; (ii) the NA was markedly higher (P < 0.05) in the diabetic group; (iii) the CA did not exhibit a statistically significant difference (P > 0.05) between these two groups; and (iv) the C/N mean was 37.4% lower in the type II diabetic group.

Conclusions:  These results associated with clinical observations suggest that diabetes mellitus can produce alterations in oral epithelial cells, detectable by microscopy and cytomorphometry, which can be used in the diagnosis of this disease.
Unusual oral findings in dermatosparaxis (Ehlers–Danlos syndrome type VIIC)
Authors: De Coster P.J. , Malfait F. , Martens L.C. , De Paepe A.
Published: September 2003

A 13‐year‐old patient with dermatosparaxis (Ehlers–Danlos syndrome type VIIC), an autosomal recessive disorder of procollagen‐I‐N‐proteinase, is presented. The oral findings comprise micrognathia, hypodontia, localized microdontia, opalescent tooth discoloration, root dysplasia, pulp obliteration, severe gingival hyperplasia, frontal open bite, and severe restriction of TMJ mobility. The reported anomalies suggest the need for expanding the present phenotypic spectrum. This is the first report on oral findings in the syndrome.
Elevated expression of cyclooxygenase (COX)‐2 in oral squamous cell carcinoma – evidence for COX‐2 induction by areca quid ingredients in oral keratinocytes
Authors: Tang Deh‐Wei , Lin Shu‐Chun , Chang Kuo‐Wei , Chi Chin‐Wen , Chang Che‐Shoa , Liu Tsung‐Yun
Published: September 2003

Background:  Elevated expression of cyclooxygenase (COX)‐2 has been demonstrated in several human cancers. Whether COX‐2 is up‐regulated in areca quid (AQ) related oral squamous cell carcinoma (OSCC) is unknown and the potential of AQ ingredients to induce COX‐2 expression has not been studied.

Methods:  COX‐2 expression was analyzed by immunohistochemistry and RT‐PCR in oral tissues. The COX‐2 mRNA and protein induction potential of AQ ingredients were analyzed by real‐time RT‐PCR and Western blotting in normal human oral keratinocyte (NHOK).

Results:  COX‐2 protein expression was significantly higher (P < 0.01) in OSCC (n = 27) as compared to their adjacent non‐cancerous matched tissue (NCMT). COX‐2 protein was nearly undetectable in control normal oral mucosa. The level of COX‐2 mRNA was markedly elevated in 63% (12/19) of OSCC compared to NCMT. Hydroxychavicol induced COX‐2 mRNA and protein expression in NHOK.

Conclusions:  COX‐2 protein as well as mRNA expression were significantly enhanced in OSCC as compared to NCMT. Hydroxychavicol, a unique ingredient in AQ, induced COX‐2 expression in NHOK, which highlighted early involvement of COX‐2 in AQ‐associated oral oncogenesis.
The M‐PMV Cytoplasmic Targeting‐Retention Signal Directs Nascent Gag Polypeptides to a Pericentriolar Region of the Cell
Authors: Sfakianos Jeffrey N. , LaCasse Rachel A. , Hunter Eric
Published: September 2003

Intracytoplasmic protein targeting in mammalian cells is critical for organelle function as well as virus assembly, but the signals that mediate it are poorly defined. We show here that Mason‐Pfizer monkey virus specifically targets Gag precursor proteins to the pericentriolar region of the cytoplasm in a microtubule dependent process through interactions between a short peptide signal, known as the cytoplasmic targeting‐retention signal, and the dynein/dynactin motor complex. The Gag molecules are concentrated in pericentriolar microdomains, where they assemble to form immature capsids. Depletion of Gag from this region by cycloheximide treatment, coupled with the presence of ribosomal clusters that are in close vicinity to the assembling capsids, suggests that the dominant N‐terminal cytoplasmic targeting‐retention signal functions in a cotranslational manner. Transport of the capsids out of the pericentriolar assembly site requires the env‐gene product, and a functional vesicular transport system. A single point mutation that renders the cytoplasmic targeting‐retention signal defective abrogates pericentriolar targeting of Gag molecules. Thus the previously defined cytoplasmic targeting‐retention signal appears to act as a cotranslational intracellular targeting signal that concentrates Gag proteins at the centriole for assembly of capsids.
M‐PMV Capsid Transport Is Mediated by Env/Gag Interactions at the Pericentriolar Recycling Endosome
Authors: Sfakianos Jeffrey N. , Hunter Eric
Published: September 2003

Cytoplasmic transport of Gag molecules to the site of budding is an important but poorly understand process in retroviral assembly. Our previous studies of Mason‐Pfizer monkey virus showed that, for this retrovirus, Gag is assembled into capsids at a pericentriolar region and that Env is necessary for efficient transport out of the site. An Env requirement for cytoplasmic transport implicates vesicular trafficking in this process even though the capsids remain cytoplasmic and do not bud into intracellular compartments in the cells studied to date. We show here that the secretory pathway of the cell is not directly involved in Gag transport since the latter was not inhibited by BFA, nor did Gag colocalize with markers of the ER, Golgi, or TGN. Instead, colocalization was observed between Gag and endocytosed transferrin and with Rab11, suggesting that pericentriolar recycling endosomes play a critical role in this process. Mutants of Rab11 that inhibit efflux of transferrin from the recycling endosome also inhibited Gag transport. Our studies show that Env colocalizes with Gag at the pericentriolar assembly site, and provide evidence that Env must travel through this compartment in order to initiate export of the capsids from the site of assembly. Thus, for the first time, endocytic trafficking of a retroviral Env glycoprotein is linked to the efficient cytoplasmic transport of Gag.
Tying Everything Together: The Multiple Roles of Cysteine String Protein (CSP) in Regulated Exocytosis
Authors: Evans Gareth J. O. , Morgan Alan , Burgoyne Robert D.
Published: September 2003

In addition to the core vesicle fusion machinery, the SNARE proteins, a large number of regulatory proteins have been implicated in the process of Ca2+‐dependent exocytosis. How these exocytotic proteins are properly targeted and how their myriad interactions are temporally and spatially coordinated is poorly understood. Cysteine string protein (CSP), a secretory vesicle membrane protein and a member of the dnaJ family of co‐chaperones, may assist in performing this function. Through its interaction with the ubiquitous chaperone, Hsc70, it is thought that cysteine string protein targets chaperone complexes to the exocytotic machinery to facilitate the correct folding of polypeptides or to regulate the assembly of protein complexes. Since its discovery, there have been conflicting reports from different systems concerned with whether cysteine string protein exerts its effects on exocytosis either up‐ or down‐stream of Ca2+‐influx. In this review, we summarize recent experiments that associate cysteine string protein with the regulation of vesicle filling, vesicle docking, Ca2+‐channels and the SNARE proteins themselves, hence supporting a role for cysteine string protein as a multifunctional secretory co‐chaperone. In addition, we provide an update on the mammalian isoforms of cysteine string protein following the recent discovery of two novel cysteine string proteins.
Bst‐2/HM1.24 Is a Raft‐Associated Apical Membrane Protein with an Unusual Topology
Authors: Kupzig Sabine , Korolchuk Viktor , Rollason Ruth , Sugden Anna , Wilde Andrew , Banting George
Published: September 2003

An expression screen of a rat cDNA library for sequences encoding Golgi‐localized integral membrane proteins identified a protein with an apparent novel topology, i.e. with both an N‐terminal transmembrane domain and a C‐terminal glycosyl‐phosphatidylinositol (GPI) anchor. Our data are consistent with this. Thus, the protein would have a topology that, in mammalian cells, is shared only by a minor, but pathologically important, topological isoform of the prion protein (PrP). The human orthologue of this protein has been described previously (BST‐2 or HM1.24 antigen) as a cell surface molecule that appears to be involved in early pre‐B‐cell development and which is present at elevated levels at the surface of myeloma cells. We show that rat BST‐2/HM1.24 has both a cell surface and an intracellular (juxtanuclear) location and is efficiently internalized from the cell surface. We also show that the cell surface pool of BST‐2/HM1.24 is predominantly present in the apical plasma membrane of polarized cells. The fact that rat BST‐2/HM1.24 apparently possesses a GPI anchor led us to speculate that it might exist in cholesterol‐rich lipid microdomains (lipid rafts) at the plasma membrane. Data from several experiments are consistent with this localization. We present a model in which BST‐2/HM1.24 serves to link adjacent lipid rafts within the plasma membrane.
No Difference in Natural‐killer‐T cell population, but Th2/Tc2 Predominance in Peripheral Blood of Recurrent Aborters
Authors: Shimada Shigeki , Iwabuchi Kazuya , Kato Emi H. , Morikawa Mamoru , Sakuragi Noriaki , Onoé Kazunori , Minakami Hisanori , Yamada Hideto
Published: September 2003

Problem: The aim of this study was to assess the natural‐killer‐T (NKT) cell population and cytokine expression in the peripheral blood of women with a history of recurrent spontaneous abortion (RSA).

Method of study: The percentages of CD3+CD4−CD8−TCRVα24+Vβ11+‐NKT cells and cells expressing intracellular interferon (IFN)‐γ, interleukin (IL)‐4, and tumor necrosis factor (TNF)‐α either with CD4+ or CD8+ cells were measured by flow cytometry at the midluteal phases in 15 RSA women and 15 fertile control women.

Results: No significant differences in the NKT cell percentages were found between RSA and control women. However, in RSA women, the CD4+IL‐4+ cell and CD8+IL‐4+ cell percentages were significantly higher, and the Th1/Th2 and Tc1/Tc2 cell ratios were significantly lower, than those in the control.

Conclusions: Th2/Tc2 dominance was found in the general circulation of RSA women; this finding provokes a new controversy on the Th1/Th2 balance concerning RSA etiology.
Maternal Serum Levels of Pro‐ Inflammatory Cytokines in Missed and Threatened Abortion
Authors: Paradisi Roberto , Porcu Eleonora , Venturoli Stefano , Maldini‐Casadei Mario , Boni Paola
Published: September 2003

Problem: A study of association between pro‐inflammatory cytokines, and missed and threatened abortions with good outcome has been performed.

Method of study: The presence of pro‐inflammatory cytokines, namely interleukin (IL)‐8 and IL‐12 and the soluble interleukin‐2 receptor (SIL‐2R) was investigated in maternal serum of 12 patients with threatened abortion twice (at admission and discharge), 14 patients with missed abortion, 14 women with healthy first‐trimester pregnancy, and 14 normal non‐pregnant women, using specific enzyme‐linked immunosorbent assays.

Results: SIL‐2R and, in particular, IL‐12 was detected with significantly higher levels in missed abortion group compared with all other groups. IL‐8 was detected with no significant difference among all the groups studied.

Conclusions: In spite of caution due to the small sizes of the subject samples, these results support a role of the immune system in the first trimester pregnancy and hypothesize that missed abortion may be associated with an enhanced Th1 reactivity, whereas threatened abortion with good outcome resembles the normal pregnancy with a non‐enhanced Th1 reactivity.
Effects of Fibronectin, VEGF and Angiostatin on the Expression of MMPs through Different Signaling Pathways in the JEG‐3 Cells
Authors: Zhang Jian , Cao Yu‐Jing , Li Fu‐Yang , Li Jing , Yao Li‐Bo , Duan En‐Kui
Published: September 2003

Problem: The objective of this study was to evaluate the possible signal pathway of fibronectin (FN), vascular endothelial growth factor (VEGF) and angiostatin (AS) on the expression of matrix metalloproteinases (MMPs) in JEG‐3 cells.

Methods of study: JEG‐3 cells were cultured and were examined for the effect of FN, VEGF and AS on the expression of MMPs by immunocytochemistry, gelatin zymography, Western blot analysis and reverse transcription‐polymerase chain reaction (RT‐PCR).

Results: We found that up‐regulation of the expression of MMPs was induced by FN and VEGF through the focal adhesion kinase (FAK)/mitogen‐activated protein kinase (MAPK) and Flt‐1/p38SAPK/MAPKAPK2 signaling pathways, respectively. Furthermore, AS down‐regulated the expression of MMPs through the integrin αVβ3/FAK signaling pathway independent of the integrin‐binding motif Arg‐Gly‐Asp (RGD).

Conclusion: These data indicate that the expression of MMPs is regulated by many independent factors (such as FN, VEGF and AS) through different signaling pathways which influence the behavior of trophoblast cells.
Predominant Intracellular Expression of CXCR4 and CCR5 in Purified Primary Trophoblast Cells from First Trimester and Term Human Placentae
Authors: Maldonado‐Estrada Juan , Menu Elisabeth , Roques Pierre , Vaslin Bruno , Dautry‐Varsat Alice , Barré‐Sinoussi Françoise , Chaouat Gérard
Published: September 2003

Problem: The aim of the present study was to define the expression of CXCR4 and CCR5 on non‐cultured non‐stimulated primary human trophoblast cells (TCs) immediately after their immunopurification.

Method of study: We have evaluated by flow cytometric analysis and immunofluorescence, highly purified primary TCs prepared from first trimester (8.2 ± 0.3 weeks, n = 15) and term (Caesarean section, n = 10) placentae for the cell surface and intracellular expression of CXCR4 and CCR5.

Results: There was a high level of individual variability for CXCR4 and CCR5 expression between trophoblast batches. In first trimester and term placentae TCs, we found a greater number of TCs preparations expressing intracellular CXCR4 than CCR5 (P < 0.05). Both receptors were predominantly localized in the intracellular compartment of TCs, whatever if isolated from first trimester or term placentae.

Conclusions: The functional consequences of the predominance of CXCR4 expression and of cellular addressing are briefly discussed.
Down‐Regulation of HLA‐G1 Cell Surface Expression in Human Cytomegalovirus Infected Cells
Authors: Pizzato Nathalie , Garmy‐Susini Barbara , Le Bouteiller Philippe , Lenfant Françoise
Published: September 2003

Problem: Down‐modulation of human leukocyte antigen (HLA)‐G1 cell surface expression by human cytomegalovirus (HCMV) has only been studied in cellular models expressing independent unique short (US) recombinant proteins, but not in the context of viral infection. To explore the level of HLA‐G1 cell surface expression after HCMV infection and to investigate the influence of US viral proteins, we infected HLA‐G1 expressing cells by HCMV laboratory strains.

Method of study: Human U373‐MG astrocytoma cells were transfected with HLA‐G1 cDNA. Following HCMV infection, HLA‐G1 cell surface expression of these transfectants was evaluated by flow cytometry and confocal microscopy, using an HLA‐G specific monoclonal antibody, and compared with that of uninfected cells. US‐deleted viruses were then used to evaluate the implication of US proteins.

Results: Using flow cytometry, it was found that HCMV infection of U373‐G1 cells decreased HLA‐G1 cell surface expression. Similar results were obtained with two different HCMV strains, namely Towne and AD169. Two color confocal microscopy staining further confirmed such HLA‐G down‐modulation in HCMV‐infected cells stained for immediate early (IE1/2) nuclear proteins expression. Infection of U373‐G1 cells with US‐deleted HCMV strain had no effect on the level of cell surface HLA‐G1 expression, thus demonstrating the US dependency of the HCMV‐mediated down‐regulation of HLA‐G1.

Conclusion: HCMV infection down‐modulates HLA‐G1 expression at the cell surface. This is likely to have functional consequences in case of HCMV uterine infection during pregnancy.
Antinuclear Antibody Reduces the Pregnancy Rate in the First IVF‐ET Treatment Cycle but Not the Cumulative Pregnancy Rate without Specific Medication
Authors: Kikuchi Kumiko , Shibahara Hiroaki , Hirano Yuki , Kohno Takahiro , Hirashima Chikako , Suzuki Tatsuya , Takamizawa Satoru , Suzuki Mitsuaki
Published: September 2003

Problem: It has been shown that the presence of antinuclear antibody (ANA) might reduce pregnancy rates after in vitro fertilization‐embryo transfer (IVF‐ET). However, the mechanism of implantation failure by ANA has not yet been clarified. This study was performed to investigate the impact of ANA on pregnancy rates after IVF‐ET, and the necessity of specific medication for infertile women who have ANA in their sera.

Method of study: A total of 108 infertile women were treated by IVF‐ET or intracytoplasmic sperm injection (ICSI)‐ET. ANA was examined by an indirect fluorescent antibody procedure. Data from women under 40 years old were analyzed retrospectively.

Results: The implantation rates per embryo transferred in the first treatment cycles were 14.8% (eight of 54) and 32.4% (33 of 102), in women with and without ANA, respectively. There was a significant difference in the implantation rates between the two groups (P < 0.05). The pregnancy rates per ET in the first treatment cycles were 28% (seven of 25) and 54.2% (26 of 48), respectively. There was also a significant difference in the pregnancy rates between the two groups (P < 0.05). Afterwards, treatments with IVF‐ET or ICSI‐ET were repeatedly performed for unsuccessful patients, without any specific medication for ANA. The average ET cycles were 1.80 ± 1.13 and 1.27 ± 0.54, in women with and without ANA, respectively. The cumulative pregnancy rates per patient were 68% (17 of 25) and 55.6% (35 of 63), respectively. There was no significant difference in the overall pregnancy rates between the two groups.

Conclusions: These findings suggest that ANA might have an impact on implantation failure in women treated by IVF‐ET or ICSI‐ET. ANA reduced the pregnancy rates in the first IVF‐ET or ICSI‐ET cycles but not the cumulative pregnancy rates without medication. This indicates that the mechanisms of implantation failure by ANA could be solved, and effective and safe medication should be developed for better implantation rates, especially in the first treatment cycle.
Relation Between Post‐partum Liver Dysfunction and Anti‐cytochrome 2D6 Antibodies
Authors: Izumi Yukiko , Tanaka Susumu , Hidaka Yoh , Shimaoka Yuki , Tatsumi Ke‐ita , Takano Toru , Kaneko Akira , Oku Kazumi , Amino Nobuyuki
Published: September 2003

Problem:  Autoimmune thyroid disease frequently aggravates or develops after delivery through the immune rebound mechanism. However, little is known about the post‐partum development of autoimmune hepatitis (AIH).

Method of study:  We examined 18 patients who developed liver dysfunction after delivery or abortion. Serial examinations were performed in 10 of these cases. Anti‐cytochrome 2D6(CYP2D6) antibodies, which are liver‐specific autoantibodies, were measured using a sensitive radioligand assay.

Results:  Liver dysfunction developed between 1 and 5 months after delivery and was mild and transient except in one case. One patient developed liver dysfunction after abortion. Eight of 10 patients who underwent serial serologic examinations were positive for anti‐nuclear antibodies, but anti‐smooth muscle antibodies were positive in only three patients, and were present only at low titer. None of the patients had anti‐mitochondrial antibodies. Nine of these 10 cases were diagnosed as definite or probable AIH according to the international scoring system of AIH. Nine of these 10 patients were positive for anti‐CYP2D6 antibodies. The increase of anti‐CYP2D6 antibodies was slightly delayed compared to increase of aminotransferase. Of the 18 patients who developed liver dysfunction, 15 cases (83.3%) were positive for anti‐CYP2D6 antibodies. Of the 77 post‐partum control subjects only three (3.9%) had positive antibodies.

Conclusions:  Autoimmune hepatitis developed after delivery, similarly to the development of post‐partum autoimmune thyroid disease. Measurement of anti‐CYP2D6 antibodies by a sensitive radioligand assay could provide information important for the detection of post‐partum AIH.
Searching for Links between Endotoxin Exposure and Pregnancy Loss: CD14 Polymorphism in Idiopathic Recurrent Miscarriage
Authors: Karhukorpi Jari , Laitinen Tarja , Karttunen Riitta
Published: September 2003

Problem: Lipopolysaccharide (LPS) (endotoxin) is a well‐known inducer of abortions in mice. In addition it has been proposed that gut‐derived LPS of gram‐negative bacteria may play a role in triggering idiopathic recurrent miscarriage (IRM) in humans. CD14 is one of the key molecules that mediates the effects of LPS. Promoter region polymorphism (−159C/T) in the CD14 gene is functionally important by regulating CD14 levels. High‐producing CD14 genotype (TT) associates with deleterious effects of gut‐derived LPS in hepatic cirrhosis in humans. It is not known whether women with IRM are genetically more prone to suffer from toxic effects of LPS.

Method of study: By using polymerase chain reaction we analyzed the CD14 promoter region polymorphism in 38 women with IRM and in 127 normal controls of Finnish origin.

Results: There were no significant differences in the CD14(−159C/T) allele or the genotype frequencies between the IRM women and the controls. However, there was a trend associating the presence of the T allele with increased odds of miscarriage.

Conclusions: Although we were not able to find a statistically significant association between CD14 genotypes and IRM in our relatively small study population, a further study with a larger sample size is warranted to explore the role of high‐producing CD14 genotypes in IRM. Also studies highlighting environmental LPS triggers and other intrinsic mediators of LPS signalling are needed to solve the enigmatic role of LPS in IRM in humans.
Upregulation of Interleukin‐8 by Hypoxia in Human Ovaries
Authors: Yoshino Osamu , Osuga Yutaka , Koga Kaori , Hirota Yasushi , Yano Tetsu , Tsutsumi Osamu , Fujimoto Akihisa , Kugu Koji , Momoeda Mikio , Fujiwara Toshihiro , Taketani Yuji
Published: September 2003

Problem: To evaluate the effect of hypoxia on interleukin (IL)‐8 expression in human ovarian follicles.

Method of study: Follicular fluid (FF) from each follicle was separately collected from women undergoing in vitro fertilization and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL‐1α/β, IL‐8, and tumor necrosis factor (TNF)‐α in FF were measured. Isolated granulosa‐lutein cells (GLC) from obtained FF were cultured under normoxic or hypoxic conditions, and concentrations of IL‐8 in culture media were measured.

Results: Simple regression analysis demonstrated a significant negative correlation between the concentrations of IL‐8 and oxygen in FF (r = 0.50, P < 0.0001). However, none of the concentrations of progesterone, estradiol, IL‐1β, and TNF‐α in FF showed a significant correlation with IL‐8 concentrations. Hypoxia stimulated the secretion of IL‐8 by cultured GLC over twofolds compared with a normoxic control (P < 0.05).

Conclusions: These findings suggest that IL‐8, like other angiogenic factors, is upregulated under hypoxic condition, which argues that hypoxia in the ovarian follicles comes into play in ovarian functions by inducing a range of proangiogenic and chemoattractive substances.
Pre‐conceptional Natural Killer Cell Activity and Percentage as Predictors of Biochemical Pregnancy and Spontaneous Abortion with Normal Chromosome Karyotype
Authors: Yamada Hideto , Morikawa Mamoru , Kato Emi H. , Shimada Shigeki , Kobashi Gen , Minakami Hisanori
Published: September 2003

Problem: The aim of the present study was to determine whether pre‐conceptional natural killer (NK) cell activity and percentage are predictive of subsequent spontaneous abortion in women with recurrent spontaneous abortion (RSA).

Method of study: Pre‐conceptional NK cell activity and percentage in peripheral blood of women who had a history of two or more RSA was prospectively assessed. The 51Cr release assay and flow cytometric analysis were performed. A total of 113 RSA women were recruited, and 85 conceived later.

Results: Pre‐conceptional NK cell activity/percentage values in women whose next pregnancies ended in biochemical pregnancy and spontaneous abortion with normal fetal karyotype (n = 17, median 47%/17.1%), but spontaneous abortion with abnormal karyotype (n = 9, 27%/15.7%), were higher than those in live births (n = 59, 33%/13.1%). High values of pre‐conceptional NK cell activity (>46%; relative risk 3.6, 95%CI 1.6–8.0) and percentage (>16.4%; 4.9, 1.7–13.8) were found to predict biochemical pregnancy and spontaneous abortion with normal karyotype in the next pregnancy.

Conclusion: Pre‐conceptional NK cell abnormalities were predictive of spontaneous abortion with normal fetal karyotype.
Identification of CD4‐independent HIV Receptors on Spermatozoa
Authors: Bandivdekar Atmaram H. , Velhal Shilpa M. , Raghavan Vijaya P.
Published: September 2003

Problem: Human immunodeficiency virus (HIV) has been demonstrated to bind and enter into the spermatozoa facilitating the transmission into urogenital cells. However, spermatozoa has been reported to be devoid of the conventional CD4 receptors for HIV. This suggests that there exists an alternate modality of HIV entry into spermatozoa using receptors other than CD4. Present communication describes the identification of HIV receptors on the spermatozoa.

Method of Study: The sperm proteins were solubilized using Triton X‐100 and subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis followed by Western blot analysis, using cell‐free HIV or gp120 envelope glycoprotein as a probe. HIV or gp120 bound protein band was then visualized by using alkaline phosphatase (AP) labeled anti‐gp120 antibody as well as by using anti‐gp120 antibody and subsequently by AP‐labeled anti‐rabbit gamma globulin.

Results: The results obtained demonstrate for the first time that cell‐free HIV and gp120 protein bind specifically to 160 kDa sperm protein that could be the receptor for HIV entry into spermatozoa.

Conclusion: A 160 kDa sperm protein could be the CD4‐independent HIV receptor for HIV to bind and enter into the spermatozoa. Further characterization of this 160 kDa HIV receptor on sperm will provide an insight in understanding the mechanism and probable mode of intervention or prevention of HIV transmission at the initial stage of infection.
Influence of age on the behavior of dental pulp of dog teeth after capping with an adhesive system or calcium hydroxide
Authors: Mestrener Sandra R. , Holland Roberto , Dezan Eloi
Published: September 2003

Abstract  – This study evaluated histomorphologically the influence of chronological age of the dog on the dental pulp‐healing process after capping with the All Bond 2 system or with calcium hydroxide paste. The animals were divided according to age into young and adult groups. Class 5‐type cavities were prepared, and the pulp was submitted to an exposure of a diameter of 0.5 mm. The pulp of the teeth was then protected with the adhesive system or with a calcium hydroxide paste. Sixty days after treatment, the results obtained with the adhesive system in the young group were significantly better than those in the adult group. With calcium hydroxide, the results were similar for both groups. The pulp treated with calcium hydroxide exhibited a complete hard tissue bridge and a pulp without inflammatory reaction, a fact not observed when the adhesive system was used. In conclusion, the chronological age of the pulp influenced the comparative results only for the adhesive system (P = 0.1), and the total results were better with calcium hydroxide than with the All Bond 2 system (P = 0.01).
Dental and oral trauma and mouthguard use during sport activities in Israel
Authors: Levin Liran , Friedlander L. Daniel , Geiger Selly B.
Published: September 2003

Abstract –  The purpose of the present study was to evaluate the occurrence of oral and dental injuries in young Israeli population engaged in diverse sport activities. The participants' awareness of the use of protective devices, such as mouthguards, during sport activities was also evaluated. A population of 943 young adults, 95% males and 5% females (ages 18–19), was surveyed. A questionnaire was distributed relating to the type of sport activity practised, past oral and dental injuries over their lifetime, specifying the time and type of sports in which the injury occurred and the use and awareness of the protective devices. Of the total population examined, 850 (90%) were active in at least one type of sport, either as professionals or as amateurs. The analysis included the population that regularly participated in at least one sporting activity. The most commonly practised sports were soccer (54% of all active participants) and basketball (50%). The total number of dental and oral injuries experienced during all sport activities was 229, affecting 27% of the participants of whom 73 (9%) suffered dental injuries. Most dental injuries occurred during the basketball and soccer training sessions and matches reaching 42 and 41% of the total number of injuries, respectively, and affected 7.2 and 6.6% of the basketball and soccer players. Traumatic dental injuries in other sports occurred in less than 7% of the participants in these activities. Only 27% of the participants were aware of the protective devices, such as a mouthguards, and only 3% actually used these devices. These results point to the high risk of potential dental and oral injury during sport activities, the little knowledge about the benefits of using mouthguards and their limited utilization. The importance of public health education to increase the awareness of protective measures and devices and their actual use in Israel is the main focus. It should be a combined duty of dentists and sports physicians and of the coaches to encourage the use of protective devices during training and games.
Orthodontic movement in traumatically intruded teeth: a case report
Authors: Calasans‐Maia José de Albuquerque , Calasans‐Maia Mônica Diuana , Matta Edgard Norões Rodrigues da , Ruellas Antonio Carlos de Oliveira
Published: September 2003

Abstract  – Intrusive luxation of permanent mature teeth is one of the most serious injuries to the periodontal ligament in dental traumatology. Various treatment approaches are currently practised. The treatment of choice for traumatically intruded teeth was to combine orthodontic repositioning and endodontic treatment. This case report describes the treatment of a 50‐year‐old male patient, with four completely intruded mature permanent maxillary incisors. Orthodontic extrusion was initiated 1 week after the trauma. After 10 days, the crowns of the teeth were exposed to start endodontic therapy. Nine weeks after the injury and 8 weeks after the beginning of orthodontic extrusion, the intruded incisors were back about to their original position before the displacement occurred. All treatment management as well as a follow‐up 8 years after the trauma are described.
Prevalence and handedness correlates of traumatic injuries to the permanent incisors in 13–17‐year‐old adolescents in Erzurum, Turkey
Authors: Canakci Varol , Akgül H. Murat , Akgül Nilgün , Canakci Cenk Fatih
Published: September 2003

Abstract  – The objectives of the present study were to explore the relationship between dental trauma and handedness, and to assess the prevalence of traumatic injuries to the permanent incisors of 13–17‐year‐old patients, seeking treatment for various dental conditions in Erzurum, Turkey. A questionnaire focusing on handedness was administered to these patients. Handedness was assessed by the Edinburgh Handedness Inventory (Oldfield, 1971). Hand preference was divided into two classes for convenience in data analysis: (i) right‐handers (GSc from 80 to 100); and (ii) left‐handers (GSc from −80 to −100). This study included the 13–17‐year‐old group patients who had GSc as described above. Thus, the present study was carried out on 2180 (1252 male and 928 female, with a mean age of 14.9 years) out of 2392 patients. The clinical examinations and radiographic assessments were performed in full‐designed dental chairs. Preliminary analysis showed no differences in rates of handedness with respect to sex and age. Overall, 10.4% of the patients were left‐handers. A total of 292 (13.4%) of 2180 patients examined had one or more traumatized permanent incisors. The proportion of dental trauma was significantly higher in males than in females, 17.41% in males as compared to 7.97% in females; and ratio of the affected males to females was about 2.18. Sex difference in the prevalence of traumatized permanent incisors was statistically significant (P < 0.001). That is, males had a significantly higher risk of dental trauma than females (P < 0.001; odds ratio: 2.49; 95% confidence interval (CI) 1.88, 3.23). There was a higher level of traumatized permanent incisors among left‐handers than among right‐handers. 28.3% of left‐handers and 11.7% of right‐handers had dental trauma. This difference in the prevalence of traumatized permanent incisors for handedness was statistically significant (P < 0.001). Indeed, left‐handers had a significantly higher risk on dental trauma than right‐handers (P < 0.001; odds ratio: 3.09; 95% CI 2.23, 4.29). The primary causative factor in the occurrence of trauma was the fall (27.7%). Then came violence and fight as the second most frequent cause of trauma (24%), followed by sports injury (18.8%). Trauma resulting from collisions and traffic accidents were accounted as 13.7 and 11.3% of all cases, respectively. The other causes were 4.5%. In conclusion, the present study suggests that left‐handed adolescents have more frequent permanent incisor tooth trauma than right‐handed adolescents. Left‐handedness, therefore, appears to be a risk factor for trauma in 13–17‐year‐old adolescents.
Repair of untreated horizontal root fracture: a case report
Authors: Özbek Murat , Serper Ahmet , Çalt Semra
Published: September 2003

Abstract  – We report a clinical case of horizontal root fracture in the mandibular first premolar induced by a traffic accident. The fractured tooth spontaneously healed and diagnosed radiographically after 2 years. Fractured fragments were separated by a narrow radiolucent line and the edges were rounded, and healing of the tooth is likely to be related to interproximal connective tissue healing. Our case is an example of spontaneously healed fracture roots. An interesting finding is that the healing was observed even in the presence of two root canals, the vitality of the pulp was preserved and displacement of fragments were prevented.
Clinical outcomes for permanent incisor luxations in a pediatric population. I. Intrusions
Authors: Humphrey Janice M. , Kenny David J. , Barrett Edward J.
Published: September 2003

Abstract  – A longitudinal outcome study was undertaken to identify variables that significantly influenced tooth survival as well as pulpal and periodontal outcomes for intruded permanent maxillary incisors of children and adolescents. All cases were treated between June 1988 and June 1998 in a teaching hospital clinic. Clinical and radiographic data were collected for 26 patients (19 males, 7 females) that represented 31 permanent maxillary incisors. Mean age at the time of injury was 9.3 years (range = 5.5–17.8 years). Mean time elapsed to follow up was 1380 days (range = 65–3394 days). Survival analysis was used to identify variables significantly related to the survival and pulp necrosis (PN) for these incisors. Proportional hazards regression yielded significant prognostic models for tooth survival and the diagnosis of PN (P < 0.05). Incisors intruded >6 mm had significantly decreased survival compared with incisors intruded <3 mm (5‐year survival, 0.45 and 1.0, respectively, (P < 0.05)). Complex crown fractures were significantly related to the development of PN (P < 0.05). Logistic regression analysis showed that treatment method and severity of intrusion were related to the presence of replacement root resorption (P < 0.05). This study represents the largest sample of intruded permanent incisors examined in an outcome study of children and adolescents exclusively.
Clinical outcomes for permanent incisor luxations in a pediatric population. II. Extrusions
Authors: Lee Raymond , Barrett Edward J. , Kenny David J.
Published: September 2003

Abstract  – A longitudinal outcome study was undertaken to identify variables that significantly influenced outcomes for extruded permanent maxillary incisors of children and adolescents. Clinical and radiographic data was available for 35 patients (18 males, 17 females) representing 55 incisors. Mean age at the time of injury was 10.6 years (range: 7.1–17.8 years). Mean time elapsed to follow up was 1320 days (range: 423–2887 days). Survival analysis was used to identify variables significantly related to the prognosis of these teeth. The loss of an incisor following extrusion was uncommon as only one tooth (1/55) required extraction. There was no statistically significant difference in survival between severely extruded teeth and avulsions that had been stored in physiological media (P > 0.10). Pulp necrosis (PN) was the most common complication following injury (43%) and it most often occurred during the first year. Although not statistically significant, a trend towards increased PN was found with more severely extruded teeth (P = 0.20, relative risk = 2.08). Pulp canal obliteration (PCO) was the second most common outcome (35%). The degree of extrusion was proven to be significantly associated with the development of PCO (P = 0.03, relative risk = 0.33). Root resorption was an uncommon outcome (3/55). This study represents the first outcome data on extrusions to permanent maxillary incisors in an exclusively pediatric population.
Transient apical breakdown following tooth luxation
Authors: Cohenca Nestor , Karni Sunil , Rotstein Ilan
Published: September 2003

Abstract –  Transient apical breakdown is a sequelae of certain dental traumatic injuries where the injured tissues undergo a spontaneous process of repair with no permanent damage to the pulp. Misdiagnosis of this condition may result in unnecessary endodontic treatment. Presented is a case of transient apical breakdown following a subluxation injury of a maxillary central incisor in a 15‐year‐old girl. Four months after injury, coronal discoloration, periapical radiolucency as well as negative pulp responses to cold and electric tests were still recorded. Subsequently, the tooth spontaneously regained its original shade and the pulp responded normally to pulp sensitivity tests. Methods for early diagnosis of transient apical breakdown are discussed.
Early upregulation of kinin B1 receptors in retinal microvessels of the streptozotocin‐diabetic rat
Authors: Abdouh Mohamed , Khanjari Ashraf , Abdelazziz Nadia , Ongali Brice , Couture Réjean , Hasséssian Haroutioun M
Published: September 2003

Retinal microvessel responses to kinin B1 and B2 receptor agonists and antagonists were investigated in streptozotocin (STZ)‐diabetic rats and age‐matched controls. In addition, quantitative in vitro autoradiography was performed on retinas from control and STZ‐diabetic rats with radioligands specific for B2 ([125I]HPP‐Hoe 140), and B1 receptors ([125I]HPP‐[des‐Arg10]‐Hoe 140).

In control rats, the B2 receptor agonist bradykinin (BK, 0.1–50 nM) vasodilated retinal vessels in a concentration and time‐dependent manner. This effect was completely blocked by the B2 receptor antagonist Hoe140 (1 μM). In contrast, the B1 receptor agonist des‐Arg9‐BK (0.1–50 nM) was without effect.

Des‐Arg9‐BK was able to produce a concentration‐dependent vasodilatation as early as 4 days after STZ injection, and the effect of 1 nM des‐Arg9‐BK was inhibited by the B1 receptor antagonist des‐Arg10‐Hoe140 (1 μM). Low‐level B1 receptor binding sites were detected in control rats, but densities were 256% higher in retinas from 4‐ to 21‐day STZ‐diabetic rats.

In control rats, the vasodilatation in response to 1 nM BK involved neither calcium influx nor nitric oxide (NO) as GdCl3 and L‐NAME were without effect. However, the vasodilatation did involve intracellular calcium mobilization as well as products of the cyclooxygenase‐2 (COX‐2) pathway as 2,5‐di‐t‐butylhydroquinone (BHQ), cADP ribose and L‐745 337 inhibited this response. The vasodilatation response was blocked by trans‐2‐phenyl cyclopropylamine (TPC) demonstrating that prostacyclins mediate this response.

In STZ‐diabetic rats, the vasodilatation in response to des‐Arg9‐BK involved both calcium influx and intracellular calcium mobilization from stores both IP3 sensitive and non‐IP3 sensitive. Indeed, the effect was blocked by GdCl3, BHQ and cADP ribose. Furthermore, NO production and products of the COX‐2 pathway including prostacyclin are involved as the response was inhibited by L‐NAME, L‐745 377 and TPC.

Vasodilatation in response to either 1 nM BK or 1 nM des‐Arg9‐BK were blocked by NF023 demonstrating that a Go/Gi G‐protein transduces both these effects.

This is the first report on the retinal circulation which provides evidence for vasodilator B2 receptors and the upregulation of B1 receptors very early following induction of diabetes with STZ rats. These results suggest that kinin receptors may be potential targets for therapeutics to treat retinopathies.

British Journal of Pharmacology (2003) 140, 33–40. doi:10.1038/sj.bjp.0705210
Electrical properties of detrusor smooth muscles from the pig and human urinary bladder
Authors: Hashitani Hikaru , Brading Alison F
Published: September 2003

The electrophysiological properties of detrusor smooth muscles have been studied almost exclusively in small mammals and the relevance of the information to the human bladder has been questioned. In the present study, electrical properties of detrusor smooth muscles of the pig and human were investigated using intracellular recording techniques.

Bladder smooth muscles of the pig and human exhibited nifedipine (10 μM)‐sensitive spontaneous action potentials, and their frequency was highly sensitive to membrane polarization.

During bursts of action potentials, each action potential was followed by a fast after‐hyperpolarization (fast AHP). Charybdotoxin (CTX, 50 nM) increased the amplitude and duration of action potentials but failed to inhibit the fast AHPs, while apamin (0.1 μM) blocked the fast AHPs and induced action potential complexes, which were followed by slow AHPs. 4‐Aminopyridine (4‐AP, 1 mM) suppressed the slow AHP and increased action potential frequency.

In the human bladder, transmural stimuli initiated inhibitory junction potential‐like hyperpolarizations, which were followed by action potential discharges. The hyperpolarizations were blocked by atropine (1 μM) and by apamin (0.1 μM) but not by CTX (50 nM). In the pig bladder, transmural stimuli evoked excitatory junction potentials (EJPs), which triggered action potentials. After desensitizing P2x receptors with α,β methylene‐ATP (10 μM), nerve‐evoked responses were similar to those of human bladder.

These results indicate that detrusor smooth muscles of the pig share many features of electrical properties with those of the human. In addition to large conductance (BK) and small conductance (SK) Ca2+‐activated K+ channels, voltage‐dependent K+ (VK) channels may play an important role in the regulation of electrical activity of detrusor smooth muscles.

British Journal of Pharmacology (2003) 140, 146–158. doi:10.1038/sj.bjp.0705319