bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing varicoceles in children: results with microsurgical varicocelectomy
Authors: Schiff Jonathan , Kelly Cathy , Goldstein Marc , Schelgel Peter , Poppas Dix 
Published: January 2005

Authors from New York present their experience of elective varicocelectomy, using microsurgical techniques, in a large series of children. They found the procedure to be safe and effective, and gave a much lower complication rate than the published rate in open varicocelectomy.The results of urethroplasty in post‐traumatic paediatric urethral strictures are presented by authors from Mansoura. They found the overall success of one‐stage perineal anastomotic repair of such strictures to be excellent, with very little morbidity.OBJECTIVETo report our experience of microsurgical subinguinal varicocelectomy in boys aged ≤ 18 years.PATIENTS AND METHODSBoys aged ≤ 18 years treated with microsurgical varicocelectomy between 1996 and 2000 at one institution were retrospectively reviewed. Indications for surgery included ipsilateral testicular atrophy, large varicocele or pain. Microsurgery was assisted by an operating microscope (×10–25) allowing preservation of the lymphatics, and the testicular and cremasteric arteries. Patient age, varicocele grade, complications and follow‐up interval were recorded.RESULTSIn all there were 97 microsurgical subinguinal varicocelectomies (23 bilateral) in 74 boys (mean age 14.7 years). Left‐sided varicoceles were significantly larger (mean grade 2.9) than right‐sided (mean grade 1.4) varicoceles. The mean follow‐up was 9.6 months. There were four complications: two hydroceles, of which one resolved spontaneously after 4 months; one patient had persistent orchialgia that resolved after 8 months; and one developed hypertrophic scarring at the inguinal incision site. There were no infections, haematomas or intraoperative injuries to the vas deferens or testicular arteries. All boys were discharged home on the day of surgery.CONCLUSIONSMicrosurgical subinguinal varicocelectomy in boys is a safe, minimally invasive and effective means of treating varicoceles. Compared with published results of the retroperitoneal mass ligation technique, which has a 15% overall complication rate and a 7–9% hydrocele occurrence rate, the microsurgical subinguinal approach appears to offer less morbidity, with a 1% hydrocele rate. We consider that microsurgical subinguinal varicocelectomy offers the best results with lower morbidity than other techniques.
Ectopic adrenocortical tissue found at groin exploration in children: incidence in relation to diagnosis, age and sex
Authors: Sullivan Jonathan G. , Gohel Manj , Kinder Richard B. 
Published: January 2005

OBJECTIVETo assess the incidence of ectopic adrenocortical tissue (EACT) in the groin in children, and examine the relationship between the incidence and the underlying diagnosis, age and sex.PATIENTS AND METHODSFrom computer records, all groin explorations between 1988 and 2002 in patients ≤15 years old were identified. Cases of EACT were identified from computer histology records, and the incidence in different groups compared.RESULTSOf 935 groin explorations, EACT was identified in 25 (2.7%); there were no cases in girls. The incidence was 0.7% at inguinal herniotomy (IH), 4.1% at ligation of the patent processus vaginalis for communicating hydrocele (P = 0.03 vs IH), and 3.3% at exploration for undescended testes (P = 0.02 vs IH). In boys with undescended testes the incidence of EACT was similar in different age groups (0–7 years, 3.3%; 8–15 years 3.2%, P= 0.96).CONCLUSIONSThe overall incidence of EACT at groin exploration was 2.7%, with none detected in girls. There was no evidence of involution of EACT with increasing age. The incidence of EACT varied with the underlying diagnosis, but the reason for this is unknown.
Cystitis glandularis in children
Authors: Capozza Nicola , Collura Giuseppe , Nappo Simona , De Dominicis Mauro , Francalanci Paola , Caione Paolo 
Published: January 2005

OBJECTIVETo assess the characteristics of cystitis glandularis in children.PATIENTS AND METHODSThree cases of cystitis glandularis in children are described, occurring in boys aged 9–13 years. The presenting symptoms were gross haematuria in the first patient and frequency and urgency in the second. The third patient was asymptomatic and the lesion appeared as a wide thickening of the bladder wall on follow‐up ultrasonography for previous surgery. In all patients, a polypoid bladder mass was found at cystoscopy and diagnosed at histology. The endoscopic resection, with long‐term antibiotic prophylaxis, was the treatment of choice, with no recurrence at 12–30 months of follow‐up.CONCLUSIONCystitis glandularis has been rarely described in children, and is probably related to chronic or recurrent infections or an inflammatory reaction. Its potential premalignant significance is still the subject of debate.
Inhibition of Ki‐67 in a renal cell carcinoma severe combined immunodeficiency disease mouse model is associated with induction of apoptosis and tumour growth inhibition
Authors: Kausch Ingo , Jiang Hai , Ewerdwalbesloh Nina , Doehn Christian , Krüger Stefan , Sczakiel Georg , Jocham Dieter 
Published: January 2005

OBJECTIVETo evaluate the effects of suppressing the expression of Ki‐67 (expressed in proliferating cells) by antisense oligonucleotides (asON) directed against Ki‐67 (which specifically inhibit the proliferation of tumour cells and tumour growth in cell culture and in subcutaneous murine tumour models) on the growth, cell viability and angiogenic activity of a preclinical renal cell carcinoma (RCC) severe combined immunodeficiency disease (SCID) mouse model.MATERIALS AND METHODSHuman RCC cells (SK‐RC‐35) were incubated with asON and control ON in the presence of a cationic lipid in monolayer cell culture. To test Ki‐67 as a target for antitumour therapy in more complex models, asON were administered to three‐dimensional RCC (SK‐RC‐35) spheroid cultures and to SCID mice bearing subcutaneous SK‐RC‐35 xenografts. For animal studies, 1 × 106 SK‐RC‐35 cells were implanted subcutaneously. Subsequently, asON or ON were injected intraperitoneally daily for 14 days at 10 mg/kg/day. Tumour size, weight and status of metastasis were documented daily and after death, respectively. The number of apoptotic cells, Ki‐67‐positive cells and the microvessel density in tumour sections was determined immunohistochemically. Quantitative reverse transcription‐polymerase chain reaction of Ki‐67 mRNA was also assessed for the tumours.RESULTSTreatment of RCC cells with asON resulted in a specific inhibition of cell growth in monolayer and spheroid cell culture. Systemic administration of Ki‐67‐directed asON significantly decreased tumour growth (P = 0.009) in SCID mice. Immunohistochemical staining of tumour specimens showed stronger inhibition of Ki‐67‐positive cells in asON‐treated tumours (mean 27.8%) than in controls (mean 42.5–57%). Furthermore, there were about twice as many apoptotic cells after asON treatment. There was no significant difference among treatment groups for microvessel density.CONCLUSIONThese results indicate that Ki‐67 represents a suitable antiproliferative target, and that asON are a potent agent inhibiting tumour growth and apoptosis, but not tumour vascularization, in human RCC.
Evaluation of hypoxia‐inducible factor 1α overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma
Authors: Theodoropoulos Vasilios. E. , Lazaris Andreas. C. , Kastriotis Ioannis , Spiliadi Chariclia , Theodoropoulos George E. , Tsoukala Vasiliki , Patsouris Efstratios , Sofras Frank 
Published: January 2005

OBJECTIVESTo investigate the possible role of hypoxia‐inducible factor 1α (HIF‐1α, a transcription factor important in regulating O2 homeostasis and physiological responses to oxygen deprivation) in the recurrence and progression of superficial urothelial bladder cancer, and to examine its expression in relation to proliferation status, apoptotic activity and intratumoral angiogenesis.PATIENTS AND METHODSParaffin wax‐embedded tissue from 140 patients with superficial primary urothelial bladder carcinoma was immunostained for HIF‐1α, Ki‐67, single‐stranded DNA antibody for apoptotic cells, p53, bcl‐2, vascular endothelial growth factor and CD31 antigen. We calculated the proliferative rate, the apoptotic index and the microvessel density (MVD). The mean (sem) follow‐up was 46 (3.5) months, within which 86 patients relapsed while 18 progressed to a higher tumour stage and/or grade.RESULTSHIF‐1α expression was more common in high‐grade superficial urothelial carcinomas. The positivity was related to increased proliferative activity (P = 0.012), apoptotic rate (P = 0.006) and MVD (P < 0.001). HIF‐1α overexpression had a marginal adverse influence on progression‐free survival (P = 0.058; univariate analysis), but when combined with p53 overexpression, the unfavourable impact was statistically important (P = 0.028). In multivariate analysis, only grade and the high Ki‐67 labelling index were significant predictors of recurrence‐free survival, while T‐stage and the HIF‐1α+/p53+ phenotype emerged as the only independent variables of adverse prognostic significance for time to progression.CONCLUSIONSHIF‐1α overexpression combined with aberrant mutant p53 nuclear protein accumulation seem to indicate an aggressive phenotype, suggesting a potential biological model predictive of future risk of disease progression in patients with superficial urothelial bladder carcinoma. These indicators may be helpful in clinical practice to discriminate superficial bladder cancer worth a more intensive follow‐up, or more aggressive treatment.
Interleukin‐4 gene intron‐3 polymorphism is associated with transitional cell carcinoma of the urinary bladder
Authors: Tsai Fuu‐Jen , Chang Chao‐Hsiang , Chen Chang‐Chung , Hsia Te‐Chun , Chen Huey‐Yi , Chen Wen‐Chi 
Published: January 2005

OBJECTIVETo evaluate whether polymorphism of the interleukin‐4 gene exon 3, and of the interleukin‐1β gene exon 5 and promoter region, are associated with transitional cell carcinoma (TCC) of the urinary bladder, as cytokines are hypothesized to be important in cancer formation.PATIENTS, SUBJECTS AND METHODSThe study included 138 patients with TCC of urinary bladder and 105 healthy controls living in the same area. Each genetic polymorphism was typed using polymerase chain reaction‐based restriction analysis. Genotype distribution and allelic frequencies between patients and controls were compared.RESULTSThere were significant differences in genotype and allelic distribution of intron 3 RP1/RP2 polymorphism (P < 0.001), but no significant difference in genotype distribution or allelic frequencies of the interleukin‐1β gene polymorphism between patients with bladder cancer and controls.CONCLUSIONThe interleukin‐4 gene intron 3 polymorphism is associated with bladder cancer and is a potential genetic marker in screening for the possible causes of bladder cancer.
In vivo accumulation of different hypericin ion pairs in the urothelium of the rat bladder
Authors: Huygens Ann , Kamuhabwa Appolinary R. , Van Cleynenbreugel Ben , Van Poppel Hendrik , Roskams Tania , De Witte Peter A.M. 
Published: January 2005

OBJECTIVETo optimise the diagnostic and phototherapeutic efficacy of hypericin in superficial bladder cancer, by developing a bladder instillation fluid that does not depend on the presence of plasma proteins for an appropriate and reliable urothelial uptake of hypericin.MATERIALS AND METHODSSodium hypericinate (in distilled water, in sodium phosphate buffer, or in polyethylene glycol) and several other hypericinate salts (potassium, lysine, TRIS or hexylamine) were instilled with no plasma constituents into the rat bladder. The accumulation of hypericin was assessed with fluorescence microscopy.RESULTSThe diagnostic and phototherapeutic efficacy of hypericin depends on its ability to penetrate the tumour lesions sufficiently to show a fluorescent signal or elicit a photodynamic response. Several instillation fluids meet the purpose, as the urothelial accumulation of hypericin was similar to that obtained with the instillation fluid supplemented with plasma proteins, used in clinical practice. The highest concentrations of hypericin in the urothelium of the rat bladder were obtained with hypericin instillation solutions prepared with distilled water or 20% polyethylene glycol 400 in distilled water. Fluorescence microscopy showed that hypericin was selectively localized in the urothelium. Furthermore, all variables investigated (hydrophilic/lipophilic balance, pH, saline, presence of organic solvent) can dramatically influence the in vivo accumulation of hypericin.CONCLUSIONAn appropriate and reliable urothelial uptake of hypericin does not depend on the presence of plasma protein supplements in the bladder instillation fluid.
Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly
Authors: Wiethoff Christopher M. , Wodrich Harald , Gerace Larry , Nemerow Glen R. 
Published: January 2005

ABSTRACT

In contrast to enveloped viruses, the mechanisms involved in membrane penetration by nonenveloped viruses are not as well understood. In these studies, we determined the relationship between adenovirus (Ad) capsid disassembly and the development of membrane lytic activity. Exposure to low pH or heating induced conformational changes in wild-type Ad but not in temperature-sensitive Ad (
ts
1) particles that fail to escape the early endosome. Wild-type Ad but not
ts
1 particles permeabilized model membranes (liposomes) and facilitated the cytosolic delivery of a ribotoxin. Alterations in wild-type Ad capsids were associated with the exposure of a pH-independent membrane lytic factor. Unexpectedly, this factor was identified as protein VI, a 22-kDa cement protein located beneath the peripentonal hexons in the viral capsid. Recombinant protein VI and preprotein VI, but not a deletion mutant lacking an N-terminal amphipathic α-helix, possessed membrane lytic activity similar to partially disassembled virions. A new model of Ad entry is proposed based on our present observations of capsid disassembly and membrane penetration.
Interactions between Natural Killer Cells and Antibody Fc Result in Enhanced Antibody Neutralization of Human Immunodeficiency Virus Type 1
Authors: Forthal Donald N. , Landucci Gary , Phan Tran B. , Becerra Juan 
Published: January 2005

ABSTRACTAntibodies can prevent lentivirus infections in animals and may play a role in controlling viral burden in established infection. In preventing and particularly in controlling infection, antibodies likely function in the presence of large quantities of virus. In this study, we explored the mechanisms by which antibodies neutralize large inocula of human immunodeficiency virus type 1 (HIV-1) on different target cells. Immunoglobulin G (IgG) from HIV-infected patients was tested for neutralizing activity against primary R5 strains of HIV-1 at inocula ranging from 100 to 20,000 50% tissue culture infective doses. At all virus inocula, inhibition by antibody was enhanced when target cells for virus growth were monocyte-depleted, peripheral blood mononuclear cells (PBMCs) rather than CD4+lymphocytes. However, enhanced inhibition on PBMCs was greatest with larger amounts of virus. Depleting PBMCs of natural killer (NK) cells, which express Fc receptors for IgG (FcγRs), abrogated the enhanced antibody inhibition, whereas adding NK cells to CD4+lymphocytes restored inhibition. There was no enhanced inhibition on PBMCs when F(ab′)2was used. Further experiments demonstrated that the release of β-chemokines, most likely through FcγR triggering of NK cells, contributed modestly to the antiviral activity of antibody on PBMCs and that antibody-coated virus adsorbed to uninfected cells provided a target for NK cell-mediated inhibition of HIV-1. These results indicate that Fc-FcγR interactions enhance the ability of antibody to neutralize HIV-1. Since FcγR-bearing cells are always present in vivo, FcγR-mediated antibody function may play a role in the ability of antibody to control lentivirus infection.
Leucine-Specific, Functional Interactions between Human Immunodeficiency Virus Type 1 Nef and Adaptor Protein Complexes
Authors: Coleman Scott H. , Van Damme Nanette , Day John R. , Noviello Colleen M. , Hitchin Douglas , Madrid Ricardo , Benichou Serge , Guatelli John C. 
Published: January 2005

ABSTRACTThe human immunodeficiency virus type 1 virulence protein Nef interacts with the endosomal sorting machinery via a leucine-based motif. Similar sequences within the cytoplasmic domains of cellular transmembrane proteins bind to the adaptor protein (AP) complexes of coated vesicles to modulate protein traffic, but the molecular basis of the interactions between these motifs and the heterotetrameric complexes is controversial. To identify the target of the Nef leucine motif, the native sequence was replaced with either leucine- or tyrosine-based AP-binding sequences from cellular proteins, and the interactions with AP subunits were correlated with function. Tyrosine motifs predictably modulated the interactions between Nef and the μ subunits of AP-1, AP-2, and AP-3; heterologous leucine motifs caused little change in these interactions. Conversely, leucine motifs mediated a ternary interaction between Nef and hemicomplexes containing the σ1 plus γ subunits of AP-1 or the σ3 plus δ subunits of AP-3, whereas tyrosine motifs did not. Similarly, only leucine motifs supported the Nef-mediated association of AP-1 and AP-3 with endosomal membranes in cells treated with brefeldin A. Functionally, Nef proteins containing leucine motifs down-regulated CD4 from the cell surface and enhanced viral replication, whereas those containing tyrosine motifs were inactive. Apparently, the interaction of Nef with the μ subunits of AP complexes is insufficient for function. A leucine-specific mode of interaction that likely involves AP hemicomplexes is further required for Nef activity. The μ and hemicomplex interactions may cooperate to yield high avidity binding of AP complexes to Nef. This binding likely underlies the unusual ability of Nef to induce the stabilization of these complexes on endosomal membranes, an activity that correlates with enhancement of viral replication.
Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3
Authors: Spiegel Martin , Pichlmair Andreas , Martínez-Sobrido Luis , Cros Jerome , García-Sastre Adolfo , Haller Otto , Weber Friedemann 
Published: January 2005

ABSTRACTSevere acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. We and others have previously shown that the replication of SARS-CoV can be suppressed by exogenously added interferon (IFN), a cytokine which is normally synthesized by cells as a reaction to virus infection. Here, we demonstrate that SARS-CoV escapes IFN-mediated growth inhibition by preventing the induction of IFN-β. In SARS-CoV-infected cells, no endogenous IFN-β transcripts and no IFN-β promoter activity were detected. Nevertheless, the transcription factor interferon regulatory factor 3 (IRF-3), which is essential for IFN-β promoter activity, was transported from the cytoplasm to the nucleus early after infection with SARS-CoV. However, at a later time point in infection, IRF-3 was again localized in the cytoplasm. By contrast, IRF-3 remained in the nucleus of cells infected with the IFN-inducing control virus Bunyamwera delNSs. Other signs of IRF-3 activation such as hyperphosphorylation, homodimer formation, and recruitment of the coactivator CREB-binding protein (CBP) were found late after infection with the control virus but not with SARS-CoV. Our data suggest that nuclear transport of IRF-3 is an immediate-early reaction to virus infection and may precede its hyperphosphorylation, homodimer formation, and binding to CBP. In order to escape activation of the IFN system, SARS-CoV appears to block a step after the early nuclear transport of IRF-3.
Human Cytomegalovirus Genes in the 15-Kilobase Region Are Required for Viral Replication in Implanted Human Tissues in SCID Mice
Authors: Wang Weijia , Taylor Shannon L. , Leisenfelder Stacey A. , Morton Robert , Moffat Jennifer F. , Smirnov Sergey , Zhu Hua 
Published: January 2005

ABSTRACT

Since animal models for studying human cytomegalovirus (HCMV) replication in vivo and pathogenesis are not available, severe combined immunodeficiency mice into which human tissues were implanted (SCID-hu mice) provide an alternative and valuable model for such studies. The HCMV clinical isolates, including those of the Toledo strain, replicate to high titers in human tissue implanted into SCID mice; however, the attenuated AD169 strain has completely lost this ability. The major difference between Toledo and AD169 is a 15-kb segment, encoding 19 open reading frames, which is present in all virulent strains but deleted from attenuated strains. This fact suggests that crucial genes required for HCMV replication in vivo are localized to this region. In this study, the importance of this 15-kb segment for HCMV replication in vivo was determined. First, Toledo
BAC
virus (produced from a Toledo bacterial artificial chromosome) and AD169 virus were tested for growth in SCID-hu mice. Toledo
BAC
, like Toledo, grew to high titers in implanted human thymus and liver tissues, while AD169 did not. This outcome showed that the Toledo genome propagated in bacteria (Toledo
BAC
) retained its virulence. The 15-kb segment was then deleted from Toledo
BAC
, and the resulting virus, Toledo
Δ15kb
, was tested for growth in both human foreskin fibroblast (HFF) cells and SCID-hu mice. Toledo
Δ15kb
had a minor growth defect in HFF but completely failed to replicate in human thymus and liver implants. This failure to grow was rescued when the 15-kb region was inserted back into the Toledo
Δ15kb
genome. These results directly demonstrated that the genes located in the 15-kb segment are crucial for HCMV replication in vivo.
Human Dendritic Cells Transduced with Herpes Simplex Virus Amplicons Encoding Human Immunodeficiency Virus Type 1 (HIV-1) gp120 Elicit Adaptive Immune Responses from Human Cells Engrafted into NOD/SCID Mice and Confer Partial Protection against HIV-1 Challenge
Authors: Gorantla Santhi , Santos Kathlyn , Meyer VaKara , Dewhurst Stephen , Bowers William J. , Federoff Howard J. , Gendelman Howard E. , Poluektova Larisa 
Published: January 2005

ABSTRACTSmall-animal models are needed to test human immunodeficiency virus (HIV) vaccine efficacy following viral challenge. To this end, we examined HIV-1-specific immune responses following immunization of nonobese diabetic-severe combined immunodeficient mice that were repopulated with human peripheral blood lymphocytes (hu-PBL-NOD/SCID mice). Autologous dendritic cells (DC) were transduced ex vivo with replication-defective, helper virus-free, herpes simplex virus type 1 (HSV-1) amplicons that expressed HIV-1 gp120 and were then injected into the hu-PBL-NOD/SCID mice. This resulted in primary HIV-1-specific humoral and cellular immune responses. Serum samples from vaccinated animals contained human immunoglobulin G that reacted with HIV-1 Env proteins by enzyme-linked immunosorbent assay and neutralized the infectivity of HIV-1 LAI and ADA strains. T cells isolated from the mice responded to viral antigens by producing gamma interferon when analyzed by enzyme-linked immunospot assay. Importantly, exposure of the vaccinated animals to infectious HIV-1 demonstrated partial protection against infectious HIV-1 challenge. This was reflected by a reduction in HIV-1ADAand by protection of the engrafted human CD4+T lymphocytes against HIV-1LAI-induced cytotoxicity. These data demonstrate that transduction of DC by HSV amplicon vectors expressing HIV-1 gp120 induce virus-specific immune responses in hu-PBL-NOD/SCID mice. This mouse model may be a useful tool to evaluate human immune responses and protection against viral infection following vaccination.