bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccines: An Ongoing Promise?
Authors: Alsahli Mazen , Farrell Richard J. , Michetti Pierre
Published: April 2003

Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed.
Basic Pathophysiologic Mechanisms in Irritable Bowel Syndrome
Authors: Mayer Emeran A. , Naliboff Bruce D. , Chang Lin
Published: April 2003

Converging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events.
Molecular Mechanisms of Hepatitis B Virus-Associated Liver Cancer
Authors: Rabe Christian , Cheng Bin , Caselmann Wolfgang H.
Published: April 2003

Hepatitis B infection is associated with an increased risk of hepatocellular carcinoma development. Hepatitis B proteins, such as the hepatitis B x protein, the large hepatitis B surface protein, or truncated middle hepatitis B surface proteins, regulate transcription of many candidate genes for liver carcinogenesis by trans-mechanisms. They also alter mechanisms of apoptosis and interfere with nucleotide excision repair of damaged DNA. Together with an influence on cellular signaling, these mechanisms may favor the cell’s clonal expansion.
Role of Percutaneous Ethanol Injection in the Treatment of Hepatocellular Carcinoma
Authors: Livraghi Tito
Published: April 2003

In the treatment of early and intermediate hepatocellular carcinoma, the range of indications for percutaneous ablation techniques is becoming wider than surgery or intra-arterial therapies. Indeed, whereas for some years only patients with up to three small tumors were treated, with the introduction of the single-session percutaneous ethanol injection (PEI), performed under general anesthesia, even patients with more advanced disease are now being treated. Although it is understood that partial resection assures the highest local control, the survival rates after surgery are roughly comparable with PEI. The explanation for this is a balance among the advantages and disadvantages of the two therapies. PEI survival curves are better than curves for resected patients who present adverse prognostic factors, and this means that surgery needs a better selection of the patients. Indications for both therapies are reported. An open question remains the choice between PEI and other new ablation procedures. In our department we currently use radiofrequency ablation in the majority of patients but consider PEI and segmental transarterial chemoembolization complementary, and use them according to the features of the disease and the response.
Gene Therapy of Hepatocellular Carcinoma
Authors: Ruiz Juan , Mazzolini Guillermo , Sangro Bruno , Qian Cheng , Prieto Jesús
Published: April 2003

The extraordinary versatility of gene therapy opens new possibilities for the treatment of incurable diseases, including hepatocellular carcinoma. Gene therapy strategies against tumors include prodrug activation therapy by the transfer of suicide genes, immunogene therapy, tumoral cell phenotype correction by the inhibition of oncogenes or the transfer of tumor suppressor genes, antiangiogenesis and transfer of oncolytic viruses. The experience accumulated during the last decade of clinical gene therapy indicates that genes can be expressed inside the tumor tissue, but the overall results of the studies conducted so far are still disappointing, mainly due to the poor performance of the currently available gene therapy vectors. This review covers the general aspects of gene therapy vectors, preclinical data available in animal models of hepatocellular carcinoma, and finally a brief summary of the gene therapy clinical trials aimed at the treatment of liver cancer.
Intracellular Accumulation of Middle Hepatitis B Surface Protein Activates Gene Transcription
Authors: Schlüter Volker , Rabe Christian , Meyer Markus , Koshy Rajen , Caselmann Wolfgang H.
Published: April 2003

While the natural intact protein does not possess any transactivator function, C-terminal truncation of the middle hepatitis B surface (MHBs) protein yields a novel transactivator function. We have previously found that the truncated transactivator protein, MHBst167, is not secreted but retained within the secretory pathway. Here, we provide evidence that when full-length MHBs is coexpressed with the truncated MHBst167 protein, the secretion of the full-length protein is inhibited and both proteins accumulate within the cell. We further show that MHBs, forcibly retained in the cell by C-terminal fusion to the endoplasmic reticulum retention signal KDEL (MHBsKDEL), mimics the effects of MHBst167 in enhancing the nuclear-binding activity of transcription factors NFĸB and AP-1, and activation of NFĸB- and AP-1-dependent transcription of reporter genes. As is the case for MHBst167, MHBsKDEL-dependent activation of NFĸB is inhibited by the antioxidant N-acetyl-L-cysteine indicating the involvement of reactive oxygen intermediates and suggesting a similar mechanism of activation. This study suggests that the intracellular retention and accumulation of the normally secreted MHBs leads to oxidative stress and activation of transcription. This may be an important but not exclusive mechanism in hepatocarcinogenesis.
Prevention and Cure of Complications from Multiple-Electrode Radiofrequency Treatment of Liver Tumors
Authors: Ma Kuansheng , Min Chen , Ian Huang Xiao , Jiahong Dong
Published: April 2003

Background/Aims: To determine the complication rate of multiple-electrode radiofrequency treatment of liver tumors, and their prevention and cure. Methods: 114 patients with liver tumors were treated 170 times using multiple-electrode radiofrequency. The clinical complications and their prevention and cure were observed. Results: The complication rate was 9.6%. The complications included 1 case of colon perforation, 4 cases of skin burn, 5 cases of hydrothorax, and 1 case subcutaneous hemorrhage, but none of the patient died due to these complications. Conclusion: The complication rate of multiple-electrode radiofrequency treatment of liver tumors is low and the complications could be prevented and cured.
Average Volume of Alcohol Consumption, Drinking Patterns and Related Burden of Mortality in Young People in Established Market Economies of Europe
Authors: Rehm Jürgen , Gmel Gerhard , Room Robin , Frick Ulrich
Published: April 2003

Objective: To determine the burden of mortality in young people (age 15–29) in established market economies in Europe in 1999, which is attributable to alcohol consumption. Two dimensions of alcohol consumption were considered: average volume of consumption, and patterns of drinking. Methods: Mortality data were obtained from the WHO EIP data bank, average volume data from the WHO global databank on alcohol, pattern of drinking data from a questionnaire sent out to experts, from the published literature and from the WHO global databank. Methods are explained and discussed in detail in two other contributions to this volume. Results: More than 8,000 deaths of people aged 15–29 in Europe in 1999 were attributable to alcohol. Young males show a higher proportion of alcohol-attributable deaths (12.8%) than females (8.3%). Both average volume and patterns of drinking contribute to alcohol-related death. Conclusions: Alcohol-related deaths constitute a considerable burden in young people in Europe.
Cocaine Use and the Utilisation of Drug Help Services by Consumers of the Open Drug Scene in Hamburg
Authors: Verthein Uwe , Haasen Christian , Prinzleve Michael , Degkwitz Peter , Krausz Michael
Published: April 2003

In order to describe the patterns of use in the open drug scene in Hamburg, a study was carried out among 616 drug users in the drug scene and in or in the vicinity of low-threshold institutions close to the drug scene in summer 2000. The special focus was on the prevalence of cocaine and crack use as well as on the utilisation of help services for drug users. 80% of the interviewed persons were male, the average age was 32.6 years. They had been using drugs such as heroin or cocaine for an average of 11 years. 84% had used heroin and 74% cocaine within the last 24 h. Use was intravenous for 66%. 57% used cocaine intravenously, the percentage of crack smokers was 22%. Compared to previous studies, an increase in cocaine use can be noted among the scene users in Hamburg, mainly related to intravenous cocaine use. Crack smoking has only increased slightly over the past few years. Based on cluster analysis, four consumption pattern groups can be established. The largest group (38%) mainly uses cocaine and heroin. The second group (26%) consists of polyvalent drug consumers using methadone in addition to heroin and cocaine, as well as, partially, benzodiazepines, cannabis or alcohol. Group 3 (19%) mainly uses heroin only, some of them also using methadone and/or cannabis. The fourth group (17%) is mainly related to alcohol, the greater part of them additionally using heroin. On the whole, it appears that those users who currently do not use cocaine (or crack) are in a better health and social situation. The group using only heroin (cluster 3) also compares favourably with the other three consumption pattern groups with regard to the intensity of use, consumption in public and risk behaviour. Almost all the interviewed persons are in contact with general practitioners. However, the increasing cocaine use has not been met by sufficient intervention and treatment programmes so far.
Nail-Patella Syndrome Associated with Respiratory Chain Disorder
Authors: Finsterer Josef , Stöllberger Claudia , Wanschitz Julia , Jaksch Michaela , Budka Herbert
Published: April 2003

Nail-patella syndrome (NPS) has not been described to be associated with a respiratory chain disorder (RCD) before. In a 42-year-old man with the typical phenotype of an NPS, weakness and wasting of the shoulder girdle muscles, muscle cramps, fatigability, hyperhidrosis, chest pain and creatine kinase elevation were observed. Echocardiography revealed left ventricular hypertrabeculation. Needle electromyography was myopathic, lactate stress testing was abnormal, muscle biopsy showed typical features of an RCD and mtDNA analysis revealed the A3243G MELAS mutation. In conclusion, this case demonstrates that NPS may be randomly associated with RCD. NPS patients should undergo detailed cardiological and neurological investigations, in order not to overlook a double trouble partially mimicking NPS.
Lack of Evidence for an Association between Two Genetic Polymorphisms in the Tumor Necrosis Factor Receptor 1 Gene and Multiple Sclerosis in Ashkenazi Jews
Authors: Pras E. , Aksentijevich I. , Shinar Y. , Kastner D.L. , Achiron A.
Published: April 2003

Multiple sclerosis (MS) is a multifactorial disease with a documented genetic component. Recent experimental models suggested a role for the tumor necrosis factor receptor 1 (TNFR1) in the pathogenesis of the disease. We compared the frequency of two polymorphisms from TNFR1, located in exon 1 and intron 6, in 94 Jewish Ashkenazi MS patients and 83 healthy Ashkenazi controls. No significant differences were observed for both polymorphisms between the patients and the controls. These findings suggest that genetic variants in TNFR1 do not play a significant role in Ashkenazi Jews.
Very High Prevalence of Right-to-Left Shunt on Transcranial Doppler in an Italian Family with Cerebral Autosomal Dominant Angiopathy with Subcortical Infarcts and Leukoencephalopathy
Authors: Angeli Silvia , Carrera Paola , Del Sette Massimo , Assini Andrea , Grandis Marina , Biancolini Donatella , Ferrari Maurizio , Gandolfo Carlo
Published: April 2003

Background and Purpose: Cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant hereditary disease whose clinical expression is a stepwise subcortical vascular dementia. Initial presentation of the disease involves transient or stabilized focal neurological deficits, migraine and mood changes. Recently, a high prevalence of right-to-left shunt (RLS) due to patent foramen ovale has been reported in subjects with migraine. The aim of our study was to determine the prevalence of RLS in CADASIL with and without migraine. Methods: We performed transcranial Doppler with gaseous contrast in 5 members of an Italian family with CADASIL, diagnosed by means of genetic and skin biopsy criteria. We then compared the prevalence of RLS in 40 consecutive subjects with juvenile stroke, 80 asymptomatic subjects affected by migraine with aura and 50 normal controls. Results: A very high prevalence of RLS was found in CADASIL patients (4/5, 80%), as opposed to young subjects with ischemic stroke (15/40, 37%), asymptomatic subjects with migraine (32/80, 40%) and normal controls (8/50, 16%). All the subjects with CADASIL and migraine (4/4) showed RLS. The difference between CADASIL patients and controls was highly significant (p = 0.006). Conclusions: We suggest an association between CADASIL and RLS, possibly due to the abnormal development of the endocardial cushion influenced by Notch 3 mutation. Our hypothesis needs to be tested in larger samples.
Indocyanine Green Angiographic Findings in Young Patients with Grönblad-Strandberg Syndrome
Authors: Guzey Mustafa , Arvas Sema , Akar Solmaz , Ozkan Sehirbay
Published: April 2003

Purpose: The objective of the present investigation was to define the indocyanine green (ICG) angiographic features of angioid streaks (AS) in young patients with Grönblad-Strandberg syndrome and to compare them with findings on fluorescein angiography (FA) and red-free photographs. Methods: Complete ophthalmological examination, red-free photography, FA and ICG angiography were performed on 6 patients, 4 women and 2 men, ranging in age from 21 to 33 years, with Grönblad-Strandberg syndrome. Results: ICG angiography showed AS in the form of hypofluorescent lines with numerous associated hyperfluorescent foci. The AS were more clearly visualized and were seen to be more numerous and larger by ICG angiography. Choroidal neovascularization (CNV) and macular involvement had become bilateral in all of the cases. ICG angiography allowed precise localization of CNV in some cases, but it was not much superior to FA in the determination of CNV and the visualization of ‘peau d’orange’. Conclusions: ICG angiography provides some information different from FA in the evaluation of AS, but usually neovascular complications and peau d’orange appearance could be seen more clearly in the red-free photographs and FA. The hypofluorescent AS pattern was significantly observed in young patients with Grönblad-Strandberg syndrome.
Ocular Ferning Test – Effect of Temperature and Humidity on Tear Ferning Patterns
Authors: Horwath Jutta , Ettinger Karl , Bachernegg Maria , Bodner Elizabeth , Schmut Otto
Published: April 2003

Background: The ocular ferning test is used as a diagnostic aid to evaluate patients with dry-eye disease. The ferning phenomenon is a dendritic growth form of dried tear fluid. The influence of temperature and relative humidity (rH) on the morphology of tear ferning patterns was investigated. Methods: Two microliters of tear fluid of 5 volunteers with normal tear function were dropped onto a microscope slide with a pipette and were dried in a climatic chamber at four different temperatures (20, 22, 24 and 26°C) and at four different grades of rH (30, 40, 50 and 60%) at each temperature. The dried droplet was divided according to distinct morphological features into a center, transition zone and margin. The center of the dried droplet was classified into four types according to the system of Rolando. Results: In the temperature range between 20 and 26°C, rH has a strong influence on the ferning patterns. At these temperatures, increasing rH resulted in a deterioration of type I ferning obtained at 30% rH to type II or type III at 60% rH in all subjects. Otherwise, at rH of 30, 40 and 50%, no definite influence of temperature between 20 and 26°C was observed. At an rH of 60%, the ferning patterns changed with increasing temperature from 20 to 26°C from type II to type III. Conclusion: High humidity can modify and deteriorate the ferning patterns of tear fluid from subjects with normal tear function. To obtain reproducible results using the ocular ferning test, stable conditions are necessary. An rH not higher than 50% at a temperature range between 20 and 26°C produced ferning patterns without interstitial spaces which could be related to the best quality according to the system of Rolando.
Comparative Study of Retinal Nerve Fiber Layer Loss in Normal-Tension Glaucoma and Chronic Open-Angle Glaucoma
Authors: Matsuno Kaori , Kurimoto Yasuo , Umihira Junichi , Hoya Takuo , Yoshimura Nagahisa
Published: April 2003

Purpose: To clarify whether loss of the retinal nerve fiber layer in normal-tension glaucoma (NTG) differs from that in chronic open-angle glaucoma (COAG). Methods: Using a scanning laser polarimeter, retinal nerve fiber layer thickness (RNFLT) was measured in 21 patients with NTG, 21 patients with COAG and 21 normal controls. The three groups were matched for age, and the NTG and COAG groups were matched for visual field loss. Results: The mean RNFLT was significantly less in the NTG than in the control group and less in the COAG than in the controls and NTG group. Although the correlations between the parameters of RNFLT and homotopic visual field measurements were significant in COAG, none of the correlations were significant in NTG. Conclusions: The present results suggest that loss of the retinal nerve fiber layer in NTG differs from that in COAG.
Renal Cell Carcinoma in Renal Graft Recipients and Donors: Incidence and Consequence
Authors: Wunderlich H. , Wilhelm St. , Reichelt O. , Zermann D.-H. , Börner R. , Schubert J.
Published: April 2003

Introduction and Objectives: Numerous studies have reported an increasing incidence of small renal cell carcinoma (RCC). De novo RCC in a renal allograft is a rare event and has special implications in renal transplant recipients. The objective of this study was to retrospectively evaluate the incidence of RCC in renal graft recipients and donors and to determine a procedure in cases with newly detected small renal tumors at the time of kidney preparation before transplantation. Material andMethods: We mailed a questionnaire to 38 German transplant clinics and received answers from 27 centers. A total of 10,997 renal graft recipients were included in the period of 1990–1998. Results: In 30 kidneys (0.273%) RCC was detected at the time of preparation before transplantation. There were 23 male and 3 female donors. No bilateral RCC was described. The mean age of the donors with RCC was 50.9 years (range 37–72 years). The tumors had a mean size of 2.2 cm (range 0.4–6 cm). 67% of the patients had a renal tumor smaller than 20 mm. In 26/27 centers the decision to transplant relies on the result of the immediate section for microscopic examination. 16 patients (0.145%) developed RCC 3–12 years after renal transplantation (mean 7.4 years). The mean tumor size was 2.5 cm (range 2–2.8 cm). In 50% a grade 1 and in the other 50% a grade 2 carcinoma was found. Conclusions: Because of the RCC incidence in donor candidates we recommend an ultrasound screening of the native kidneys before renal explantation and an immediate preparation of the kidney surface especially in donors older than 45 years. In cases with small renal lesions we recommend an immediate section for microscopic examination before transplantation to prevent tumor implantation into an otherwise healthy patient. The frequency of RCCs after renal transplantation necessitates careful clinical and instrumental examinations in organ-transplanted recipients both before and at regular intervals after transplantation, including the patient’s kidneys.
Combination of Transcutaneous Electrical Nerve Stimulation and Ondansetron in Preventing Cisplatin-Induced Emesis
Authors: Tan M. Özgür , Sandıkçı Zeki , Uygur M. Cemil , Arık A. İhsan , Erol Demokan
Published: April 2003

Objective: To find out whether the combination of transcutaneous electrical nerve stimulation (TENS) and ondansetron had an increased antiemetic effect. Materials and Methods: Fourteen testis and 11 bladder cancer patients were scheduled for 4 cycles of bleomycin-etoposide-cisplatin (BEP) or methotrexate-vinblastine-etoposide-cisplatin (MVEC) combination chemotherapy, respectively. At each cycle the whole cisplatin dose was given in 1 day that is 100 mg/m2/day in the BEP and 70 mg/m2/day in the MVEC protocols. Ondansetron was given at a dose of 12 mg/day and TENS was applied by commercially available ‘Relief Band’(Maven Labs, Inc., Citrus Heights, Calif., USA). The first 3 cycles of each case were blindly randomized to one of the following regimens; TENS vs. ondansetron vs. a combination of both. The regimens were applied during the administration of cisplatin and the patients were asked to report their nausea according to a scale between 0 to 10. Also for each regimen the number of emetic attacks experienced during the administration of cisplatin was recorded by the same observer. Then the scores of each regimen were compared. Results: The mean nausea scores for regimens TENS, ondansetron and TENS + ondansetron were found to be 5.12 ± 2.54, 3.0 ± 1.71 and 0.8 ± 0.96, respectively. Ondansetron was better than TENS in preventing nausea (p = 0.000). However the combination of TENS and ondansetron resulted in a significant decrease in nausea scores when compared to TENS alone (p = 0.000) or ondansetron alone (p = 0.000). The mean number of emetic attacks for the TENS, ondansetron and TENS + ondansetron regimens were 3.16 ± 1.84, 1.64 ± 1.44 and 0.56 ± 0.82, respectively. A statistically significant difference was present between the number of emetic attacks observed with the TENS + ondansetron combination and TENS alone (p = 0.000) or ondansetron alone (p = 0.001). Ondansetron was again better than TENS in preventing emetic attacks (p = 0.001). Conclusion: The use of TENS as an adjunct to ondansetron therapy has provided significant benefit in preventing nausea and emetic attacks caused by cisplatin.
Liposarcoma of the Spermatic Cord
Authors: Dündar Mehmet , Erol Haluk , Koçak İzzet , Kaçar Firuzan
Published: April 2003

A 64-year-old male presented with a 4-year history of a mass in the left scrotum. Radical orchiectomy was performed. Pathological analysis demonstrated a well-differentiated liposarcoma. No evidence of recurrence or metastasis has been noted during the 3-month follow-up without any postoperative adjuvant therapy.
Cavernositis following Intracavernous Injection of Vasoactive Drugs
Authors: Vives A. , Collado A. , Ribé N. , Segarra J. , Ruiz Castañé E. , Pomerol J.M.
Published: April 2003

Intracavernous injection is one of the most common treatments of erectile dysfunction. Infectious complications are rare, but hazardous. We report the case of a 44-year-old to stress the importance of patient supervision and drug prescription.
Surgical Management of Isolated Bilateral Adrenal Metastases from Colon Carcinoma Causing Adrenal Insufficiency
Authors: Crisci Alfonso , Cartei Giuseppe , De Antoni Pietro , Giannarini Gianluca , Moro Umberto , Selli Cesare
Published: April 2003

Adrenal insufficiency due to histologically proven bilateral metastatic adrenal involvement from colon cancer has been clinically reported only twice. Surgical treatment of bilateral adrenal metastases is seldom performed, since other metastatic localizations are usually concomitant. To the best of our knowledge, we report the first case of relatively long-term disease-free survival after bilateral adrenalectomy in a patient with adrenal insufficiency due to bilateral metastases from colon carcinoma.
Vaginal and Omental Metastasis from Superficial Bladder Cancer
Authors: Kumar Rajeev , Kumar Sunesh , Hemal Ashok K.
Published: April 2003

A 58-year-old lady, diagnosed as having superficial bladder cancer 6 years earlier presented to us with a vaginal nodule. Investigations and biopsy revealed a metastatic transitional cell carcinoma in the pelvic lymph nodes, omentum and vagina.
DNA Methylation Analysis in Immature Testicular Sperm Cells at Different Developmental Stages
Authors: Manning Martina , Lissens Willy , Weidner Wolfgang , Liebaers Inge
Published: April 2003

Testicular sperm extraction and intracytoplasmic sperm injection (TESE-ICSI) is a frequently used therapeutic option in azoospermic males. Genetic imprinting is a mechanism of gene regulation – mediated by the methylation of deoxyribonucleic acids (DNA) – by which only one of the parental copies of a gene is expressed. Whether the establishment of the genetic paternal imprint in this immature haploid sperm cell is complete and stable at this stage of maturation has never been analysed. In the present study, a highly sensitive heminested methylation-specific polymerase chain reaction for the target region 15q11–13 was developed for imprinting analysis at the single-cell level. Imprinting analysis was then carried out on DNA extracted from single diploid leucocytes (n = 25), ejaculated spermatozoa (n = 88), elongated testicular spermatids (n = 30), and round spermatids (n = 25). Amplification was obtained in 57% of the ejaculated spermatozoa, in all elongated spermatids and in 20% of the round spermatids. In the amplified samples, only the paternal imprint was detected. The maternal imprint was not found at all in any of the sperm cells; in 56% of the diploid leucocytes, the maternal and paternal imprints were detected at the same time (complete failure in the other 44%). The data reveal the completed establishment of the correct paternal imprint in ejaculated spermatozoa, elongated spermatids and amplified round spermatids. However, the high rate of amplification failure in round spermatids remains a factor of uncertainty.
Renal Angiomyolipoma Extending into the Right Atrium
Authors: Davydov M.I. , Matveev V.B. , Lukianchenko A.B. , Kudashev B.V. , Petrovichev N.N.
Published: April 2003

Renal angiomyolipomas (AMLs) are benign renal tumors that may possess the features of a malignant neoplasm, such as local and vascular invasion. We describe the diagnosis and management of a rare case of AML associated with tumor thrombus extending into the right atrium.
Role of Percutaneous Image-Guided Biopsy in the Evaluation of Renal Masses
Authors: Hara Isao , Miyake Hideaki , Hara Shoji , Arakawa Soichi , Hanioka Keisuke , Kamidono Sadao
Published: April 2003

Objective: The objective of the present study was to evaluate the indications, accuracy, complications and impact of image-guided percutaneous biopsy of renal masses. Materials and Methods: Between 1994 and 1999, percutaneous biopsies under ultrasonography or computerized tomography guidance were performed in 33 patients with renal mass (22 men and 11 women, mean age 57.5 years, range 21–88). We retrospectively analyzed the relationship between clinical and histopathological findings, and discuss the appropriateness of the indications for image-guided percutaneous biopsy in the diagnosis of renal masses. Results: The indications used in our institution were as follows: (1) clinical and radiological findings to suggest a diagnosis other than primary renal cell carcinoma (RCC) (n = 15); (2) suspicious lesions of RCC in multiple cystic renal masses (n = 7); (3) differentiation of transitional cell carcinoma of the renal pelvis from RCC (n = 7); (4) differentiation of angiomyolipoma from RCC (n = 4). Sufficient amounts of tissues were obtained from all patients for pathological diagnosis. Among 33 patients, 21 (63.6%) were diagnosed positive for malignancy, and 15 underwent surgical intervention. The histopathological findings between percutaneous biopsy and surgically resected tissue were identical in 13 cases (86.7%). No patient developed major complications requiring surgical treatment. Conclusion: If performed under appropriate selection of patients, percutaneous image-guided biopsy is a safe, reliable and accurate method of managing suspicious and/or indeterminate renal mass, and may contribute to the selection of appropriate clinical management by avoiding unnecessary procedures.
Superficial Bladder Tumors in Patients under 40 Years of Age: Clinical, Prognostic and Cytogenetic Aspects
Authors: Iori F. , De Dominicis C. , Liberti M. , Frioni D. , Vahedi M. , Leonardo C. , de Nunzio C. , Laurenti C.
Published: April 2003

Bladder carcinoma with transitional cells is the most frequent neoplasia in the urinary system, but it is quite rare in patients under 40 years of age (0.4–2%). An analysis of 21 patients under 40 and a review of other reports show that tumors in patients under 20 years old have little tendency to recur and to progress, while tumors in patients aged between 21 and 40 have a behavior pattern similar to older age groups regarding recurrence and disease progression. Preliminary results of a study using fluorescent in situ hybridization with probes for the centromere of chromosomes 7 and 17 showed a high incidence of aneusomy with regard to these chromosomes and a genetic difference between superficial tumors in the young and in adults. Using probes from chromosomes already described in bladder carcinogenesis, we obtained higher sensitivity and specificity in detecting aneuploid events.
Cadaver Fascia lata Sling in the Treatment of Intrinsic Sphincter Weakness
Authors: Vereecken R.L. , Lechat A.
Published: April 2003

Eight older women with stress incontinence caused by intrinsic urethral weakness underwent sling surgery with allogenic fascia lata. The tolerance of the material was excellent. In 1 case a secondary release of the fixation on the pecten was necessary because of too much tension; in the other cases the evolution was uneventful and resulted in perfect continence lasting for at least 2 years of follow-up.
Protons Inhibit the BKCa Channel of Rat Small Artery Smooth Muscle Cells
Authors: Schubert Rudolf , Krien Ulrike , Gagov Hristo
Published: April 2003

The regulation of the activity of calcium-activated potassium (BKCa) channels by intracellular proton ions (pHi) was investigated using the patch-clamp technique in smooth muscle cells freshly isolated from rat tail small arteries. Single-channel conductance and voltage dependence of activation were not different at pHi 7.0, 7.4 and 7.8. However, the membrane potential at which channel open probability reached 0.5 was 74 ± 5 mV (n = 6) (mean ± SE) at pHi 7.4 and 54 ± 2 mV (n = 4) at pHi 7.8 under conditions of pCa 5.9, and 30 ± 5 mV (n = 5) at pHi 7.4 and 62 ± 4 mV (n = 5) at pHi 7.0 under conditions of pCa 5.4. Furthermore, at a membrane potential of 0 mV, the pD2 for intracellular calcium ions was 5.19 ± 0.04 (n = 26) (mean ± SD) at pHi 7.8, 5.02 ± 0.05 (n = 28) at pHi 7.4, and 4.82 ± 0.05 (n = 30) at pHi 7.0. In addition, an alteration of pHi resulted in a profound change in the amplitude of BKCa currents in intact cells; it reversibly attenuated the current-voltage relationship decreasing the current by 55 ± 3% (n = 7) (p < 0.001) at 70 mV after lowering the extracellular NH4Cl concentration to decrease the calculated pHi from 7.2 to 6.8. Thus, alterations of pHi in the range from 7.0 to 7.8 did not affect single-channel conductance and voltage dependence of activation but markedly altered single BKCa channel activity as well as intact cell BKCa current amplitude, where an increase of the intracellular proton concentration inhibited this channel.
NFκB Signaling in Posthypoxic Endothelial Cells: Relevance to E-Selectin Expression and Neutrophil Adhesion
Authors: Kokura Satoshi , Rhoads Carol Ann , Wolf Robert E. , Yoshikawa Toshikazu , Granger D. Neil , Aw Tak Yee
Published: April 2003

Our previous studies have implicated the nuclear transcription factor ĸB (NFĸB) in the regulation of adhesion molecule expression in endothelial cells exposed to anoxia-reoxygenation (A/R) or a redox imbalance. The objectives of this study were (1) to define the kinetics of NFĸB activation by examining IĸBα degradation and the nuclear translocation of p65 in response to A/R or redox imbalance (induced by treatment of cells with diamide and buthionine sulfoximine) and (2) to determine whether the signal for IĸBα degradation, nuclear translocation of p65, and E-selectin-mediated neutrophil adhesion is related to the activity of protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTPase) and/or protein kinase C (PKC). The results demonstrate that both A/R and redox imbalance led to IĸBα degradation within 30 min and the concomitant appearance of p65 in the nucleus, consistent with rapid cytosolic activation of NFĸB and subsequent nuclear translocation of the activated p65 subunit. Inhibition of PKC blocked IĸBα degradation and p65 translocation in A/R-challenged, but not redox-altered, endothelial cells. However, both A/R- and redox-induced NFĸB activation was blocked by inhibition of PTK. Similarly, A/R-induced E-selectin expression and neutrophil-endothelial cell adhesion were blocked by inhibition of PKC or PTK, while only PTK inhibited the redox-induced adhesion response. Pretreatment of cells with N-acetyl cysteine effectively blocked A/R- or redox-induced IĸB degradation and significantly attenuated the respective neutrophil adhesion responses. Collectively, these findings indicate that A/R-induced E-selectin expression and neutrophil-endothelial cell adhesion are mediated by both PKC and PTK, which signal rapid activation of NFĸB. This A/R-induced NFĸB signaling response appears to be mediated, at least in part, by intracellular redox imbalance.
Reduced PO2 and Adenosine Formation Preserve Arteriolar Nitric Oxide Synthesis during Sympathetic Constriction in the Rat Intestine
Authors: Sauls Bryan A. , Boegehold Matthew A.
Published: April 2003

Previous reports by this laboratory have indicated that a flow-dependent fall in arteriolar wall PO2 may be a stimulus for the sustained release of endothelial nitric oxide (NO) during sympathetic vasoconstriction in the superfused rat intestine. In this study, we tested the hypothesis that locally formed adenosine serves as the link between the fall in local PO2 and NO synthesis under these conditions. Adenosine applied via pressurized micropipettes directly onto the wall or at a distance of 25 µm from the wall of first-order arterioles (resting diameter = 54 ± 1 µm) elicited dose-dependent dilations of 15–46% that were significantly reduced by the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10–4M). Arteriolar responses to sympathetic nerve stimulation were enhanced by 57–66% in the presence of L-NMMA or when tissue PO2 was prevented from falling under a high O2 superfusate. Adenosine deaminase (2.0 U/ml) or the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (4 × 10–4M) completely blocked the enhancing effect of L-NMMA on sympathetic constriction. These results are consistent with the hypothesis that the fall in arteriolar wall and/or tissue PO2 that accompanies sympathetic arteriolar constriction in the rat intestine can lead to local adenosine production, which in turn preserves endothelial NO release.
Intracellular Distribution of Gravin, a PKA and PKC Binding Protein, in Vascular Endothelial Cells
Authors: Grove Bryon D. , Bruchey Aleksandra K.
Published: April 2003

Gravin, a high-molecular-weight protein expressed widely in tissues and cells, is upregulated in cultured endothelial cells under conditions which suggest that it may play a role in wound repair and vascular development. In the current study, we examined the intracellular distribution of gravin to determine if it is associated with the cytoskeleton or with another intracellular compartment. Immunofluorescence microscopy of human umbilical vein endothelial cells (HUVEC) revealed that gravin had a punctate staining distribution that extended to the cell margin and did not appear to colocalize with stress fibers, microtubules, and intermediate filaments. Moreover, disruption of the cytoskeletal structures with either cytochalasin D or colchicine did not alter gravin distribution. However, confocal and immunoelectron microscopy clearly revealed that gravin was concentrated at the cell margin in close association with the plasma membrane. Immunoprecipitation of gravin from endothelial cell lysates resulted in coprecipitation of protein kinase activity that could be eluted from the immunoprecipitates with cAMP and that was inhibitable with a PKA-specific inhibitor. An anti-PKA catalytic subunit antibody reacted with a 40-kD band on immunoblots of the cAMP eluate. Immunoblots of the immunoprecipitates further revealed that PKCα coprecipitated with gravin from endothelial cell lysates. This study indicates that gravin is associated with either the plasma membrane or the membrane skeleton and may play a role in endothelial wound healing by targeting PKA and PKC to specific membrane-associated sites and regulating PKA/PKC-dependent cellular activities associated with endothelial wound healing.
Life and Death Cell Labeling in the Microcirculation of the Spontaneously Hypertensive Rat
Authors: Lim H.H. , DeLano F.A. , Schmid-Schönbein G.W.
Published: April 2003

Spontaneously hypertensive rats (SHRs) have elevated numbers of apoptotic cells. However, the extent and pattern of cell death at the microvascular level is unexplored. We developed a technique to determine early forms of cell death in vivo in the mesentery by use of the life/death indicator ethidium bromide (EB). The mesenteric microvasculature was superfused with 5 µM EB for a period of 3 min, rinsed and immediately viewed by digital fluorescence microscopy. EB-positive cell structures were observed both in the wall of microvessels as well as in the tissue parenchyma. The microvessels had about 2–4 EB-positive cell structures per 100 µm of vessel length. Larger arterioles (>25 µm) in the SHR had an increased EB-positive structure density. After normalization of the blood pressure in the SHR with adrenalectomy, no significant differences remained between Wistar-Kyoto (WKY) rats and SHRs. After dexamethasone treatment, the adrenalectomized SHRs had a higher EB-positive cell density in the smaller class of microvessels than the WKY rats. In addition, EB-positive cell fragments (0.5–2 µm) were observed in the mesentery microvessel wall, and with TUNEL labeling, they were demonstrated to represent DNA fragments. The percentage of microvessels with EB-positive fragments was higher in the SHR arterioles and capillaries. Capillaries and larger venules (>30 µm) in the SHR had higher levels of cell fragments per vessel length. After adrenalectomy, no significant differences remained between WKY rats and SHRs in any of the mcirovessel categories. When adrenalectomized rats were treated with dexamethasone, a higher number of EB-positive fragments was detected in the wall of SHR capillaries. These results indicate that the mesentery microcirculation in both strains is subject to an early and nonuniform pattern of cell death, as detected by EB, but is enhanced in selected individual microvascular segments of the SHR by a glucocorticoid-driven mechanism.
Relative Contributions of Cyclooxygenase- and Cytochrome P450 ω-Hydroxylase-Dependent Pathways to Hypoxic Dilation of Skeletal Muscle Resistance Arteries
Authors: Frisbee Jefferson C. , Roman Richard J. , Krishna U. Murali , Falck John R. , Lombard Julian H.
Published: April 2003

This study determined the contribution of prostanoids, cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid, and other potential mediators of hypoxic dilation of isolated rat skeletal muscle resistance arteries. Gracilis arteries (GA) were viewed via television microscopy and dilator responses to hypoxia (reduction in superfusate and perfusate PO2 from ∼145 to ∼40 mm Hg) were measured with a video micrometer. Hypoxic dilation of gracilis arteries was severely impaired by either endothelium removal or cyclooxygenase inhibition with indomethacin, but not by nitric oxide synthase inhibition with L-NAME. Treatment of GA with 17-octadecynoic acid (17-ODYA) alone to inhibit CP450 4A enzymes significantly reduced hypoxic dilation from control levels. Treatment of vessels with N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (MS-PPOH) to inhibit the production of epoxyeicosatrienoic acids (EETs) did not alter hypoxic dilation, although treatment with dibromo-dodecenyl-methylsulfimide (DDMS) to inhibit 20-hydroxyeicosatetraenoic acid (20-HETE) production had similar effects as 17-ODYA. Treatment of GA with 6(Z),15(Z)-20-HEDE, a competitive antagonist of the actions of 20-HETE, mimicked the effects of 17-ODYA and DDMS treatment on hypoxic dilation. These results suggest that hypoxic dilation of skeletal muscle resistance arteries primarily represents the effects of enhanced prostanoid release from vascular endothelium, although a contribution of reduced 20-HETE production via CP450 ω-hydroxylase enzymes also regulates hypoxic dilation of these vessels.
The Internal Redox Balance of the Cells Influences the Metabolism of Lipids of Dietary Origin by J774 Macrophages: Implications for Foam Cell Formation
Authors: Napolitano Mariarosaria , Rivabene Roberto , Avella Michael , Botham Kathleen M. , Bravo Elena
Published: April 2003

The effects of chylomicron remnants on lipid accumulation in J774 macrophages, and the incorporation of radioactivity from remnant lipids radiolabelled with [3H]oleate into cellular lipids was investigated. After 24 h of incubation with chylomicron remnants, there was considerable accumulation of lipid within the cells as assessed by staining with oil red O, indicating that the particles induce the formation of foam cells. Fatty acids released from the radiolabelled remnant lipids after uptake were found to be incorporated into cellular triacylglycerol (52%), phospholipid (37%) and cholesteryl ester (8%), but at higher remnant concentrations, the proportion used for triacylglycerol formation increased (up to 73%). When the macrophages were shifted into a pro-oxidising or pro-reducing state by incubation (24 h) with CuSO4 (2.5 µM) or N-acetylcysteine (5 mM), respectively, the incorporation of [3H]oleate from remnant lipid into cellular triacylglycerol and phospholipid was increased by 20–30% in the more oxidised as compared with the more reduced cells. These findings indicate that exposure of J774 macrophages to chylomicron remnants leads to the accumulation of lipid within the cells, and that this process is enhanced by pro-oxidising conditions. We conclude, therefore, that both lipids of dietary origin and the redox balance within macrophages may have a significant role in the induction of foam cell formation.
Cell-Mediated Delivery of Fibroblast Growth Factor-2 and Vascular Endothelial Growth Factor onto the Chick Chorioallantoic Membrane: Endothelial Fenestration and Angiogenesis
Authors: Ribatti Domenico , Nico Beatrice , Morbidelli Lucia , Donnini Sandra , Ziche Marina , Vacca Angelo , Roncali Luisa , Presta Marco
Published: April 2003

Fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF) exert their angiogenic activity by interacting with endothelial cells in a distinct manner. In this study, we investigated the morphological features of endothelial cells of the chick embryo chorioallantoic membrane (CAM) microvasculature after stimulation with FGF2 or VEGF. In order to provide a continuous delivery of the growth factor, we utilized a recently developed gelatin sponge/CAM assay in which a limited number of FGF2- or VEGF-transfected cells were adsorbed onto gelatin sponges and applied on the top of the CAM on day 8 of development. Their angiogenic activity was compared to that exerted by a single bolus of the corresponding growth factor. All the angiogenic stimuli induced a comparable vasoproliferative response, as demonstrated by the appearance of similar numbers of immature blood vessels within the sponge on day 12. No angiogenic response was observed in CAMs implanted with the corresponding parental cell lines or vehicle. Electron microscopy demonstrated that VEGF-overexpressing cells modified the phenotype of the endothelium of the blood vessels at the boundary between the implant and the surrounding CAM mesenchyme. The endothelial lining of 30% of these vessels showed segmental attenuations, was frequently interrupted and became fenestrated, mimicking what is observed in tumor vasculature. In contrast, the vessels consisted of continuous endothelium sealed by tight junctions in all the other experimental conditions. These results indicate that FGF2 and VEGF interact with endothelial cells of the CAM in a distinct manner. Both growth factors induce a potent angiogenic response, but only VEGF delivered in a continuous manner by its transfectants can modify the phenotype of the otherwise quiescent endothelium of CAM blood microvessels. The gelatin sponge/CAM assay may constitute a new model to study the mechanisms leading to endothelial fenestration in tumor growth.
Functional Nucleotide Receptor Expression and Sarcoplasmic Reticulum Morphology in Dedifferentiated Porcine Coronary Smooth Muscle Cells
Authors: Hill Brent J.F. , Wamhoff Brian R. , Sturek Michael
Published: April 2003

The phenotypic dedifferentiation of vascular smooth muscle cells (SMCs) is an early event associated with cell culturing and vascular injury. The purpose of this study was to evaluate the SMC phenotype underlying the functional responsiveness of SMCs to nucleotides in organ culture. Porcine coronary arteries were either used fresh, cold stored (5°C) 4 days, or organ cultured (37°C) 4 days. Fura-2 digital imaging of single SMCs was used to measure the myoplasmic calcium (Cam) response to 10 µM of the following nucleotide receptor agonists: UTP, UDP, ATP, ADP, and 2-MeSATP. In contrast to the nucleotides UDP, ATP, ADP, and 2-MeSATP, the Cam response increased 10-fold and the number of cells that responded to UTP increased 5-fold in SMCs from organ culture compared to SMCs from fresh or cold-stored arteries. Simultaneous imaging of Cam, DNA content, and SR distribution in SMCs from organ culture indicated that the UTP-induced Cam increase occurred exclusively in SMCs that had a dedifferentiated cell phenotype. Three-dimensional image reconstruction of the nucleus and sarcoplasmic reticulum (SR) revealed a novel transnuclear SR distribution that intertwined with the nucleus in fresh SMCs, while in SMCs from organ culture the SR was predominantly perinuclear and cytoplasmic. This study demonstrates that the functional up-regulation of UTP-sensitive receptors and the disappearance of the transnuclear SR distribution are novel features of dedifferentiated coronary SMCs.