bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B Virus X Protein: Structure, Function and Biology
Authors: Murakami Seishi
Published: April 2003

The X gene is conserved among mammalian hepadnaviruses and the X protein, pX, is essential for viral propagation at least in the woodchuck. During the last decade, efforts have centered on elucidating the oncogenic role of pX in hepatitis B virus infection. The accumulating knowledge on pX indicates that it is a multifunctional regulatory protein which modulates many host functions by communicating directly or indirectly with a variety of host targets as is the case for many viral regulatory proteins, such as T antigens, E1A, and human T cell lymphotropic virus tax. pX, which modulates the transcription machinery and/or modulation protein kinase signaling cascades, transactivates many host genes involved in cell proliferation, cytokine networks, acute immune response, and house-keeping functions. Distinct from the transactivation, pX also modulates DNA repair processes by interacting with p53 and/or repair enzymes which may accumulate mutations and sensitize cells to genotoxic stimuli. Several X-interaction host proteins remain to be characterized as targets of pX. The biological roles of pX have been addressed in various systems in addition to the role of pX on viral reproduction. pX may affect cell cycle progress, response to apoptotic stimuli, cell transformation, and carcinogenesis in the presence or absence of additional oncogenic factors. These biological roles of pX have not been described in terms of pX functions and targets and remain subjects of future research using improved experimental systems and technologies. Such efforts will identify important function(s) of pX for hepatocarcinogenesis.
Effect of Interleukin-6 and Tumor Necrosis Factor-α on GABA Release from Mediobasal Hypothalamus and Posterior Pituitary
Authors: De Laurentiis Andrea , Pisera Daniel , Lasaga Mercedes , Díaz María del Carmen , Theas Susana , Duvilanski Beatriz , Seilicovich Adriana
Published: April 2003

The release of cytokines during infection, inflammation and stress induces brain-mediated responses, including alterations of neuroendocrine functions. We examined the effect of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) on release of γ-aminobutyric acid (GABA) from mediobasal hypothalamic (MBH) explants and posterior pituitaries (PP) of male rats. IL-6 (10 ng/ml) did not modify basal GABA release from MBH and PP, but significantly increased GABA release under depolarizing conditions (40 mM K+). This effect was abolished by incubation of the tissue with indomethacin, an inhibitor of cyclooxygenase activity, indicating that prostaglandins could mediate the stimulation of GABA release induced by IL-6. On the contrary, TNF-α (50 ng/ml) significantly decreased K+-evoked GABA release from both MBH and PP. This inhibitory effect was not modified by indomethacin. Neither IL-6 nor TNF-α affected nitric oxide synthesis, as measured by [14C]citrulline production. The current results indicate that IL-6 stimulates GABA release from both hypothalamus and posterior pituitary by a mechanism mediated by prostaglandins. On the contrary, TNF-α inhibits GABA release from both tissues. These results suggest the possibility that GABAergic activity in the hypothalamic-pituitary axis could be involved in neuroendocrine responses to cytokines.
Central Monoamine Activity following Acute and Repeated Systemic Interleukin-2 Administration
Authors: Lacosta Susan , Merali Zul , Anisman Hymie
Published: April 2003

Interleukin-2 (IL-2), together with other cytokines, may be involved in communication between the immune system and the CNS. Moreover, IL-2 alterations have been implicated in psychiatric disorders, and IL-2 immunotherapy may engender neuropsychiatric and cognitive disturbances. Given the presumed relationship between mood disturbances and monoamine activity, the present investigation was undertaken to determine the central monoamine alterations associated with acute and repeated systemic IL-2 administration in mice. Acute, systemic IL-2 (0.55–17.6 × 103 IU) did not influence plasma adrenocorticotropic hormone or corticosterone levels, but increased the utilization of norepinephrine (NE) within the paraventricular nucleus of the hypothalamus. In contrast to the effects of acute IL-2 administration, when administered repeatedly (for 7 days), IL-2 increased NE utilization within the median eminence plus arcuate nucleus and in the hippocampus, and to a lesser extent in the central amygdala and medial prefrontal cortex. These changes in utilization were accompanied by increased levels of NE within the median eminence plus arcuate nucleus and central amygdala, and reduced NE within the locus coeruleus. As well, serotonin (5-hydroxytryptamine; 5-HT) levels were altered within the hippocampus and prefrontal cortex, and dopamine turnover was reduced within the caudate and substantia nigra. The finding of altered central neurotransmitter activity needs to be considered in the context of the marked cognitive/memory impairments, as well as the neuropsychiatric symptoms, which are associated with IL-2 immunotherapy in humans.
Lower Serum Zinc in Relation to Serum Albumin and Proinflammatory Cytokines in Detoxified Alcohol-Dependent Patients without Apparent Liver Disease
Authors: De Vos Nathalie , Song Cai , Lin Ai-hua , Demedts Paul , Wauters Annick , Neels Hugo , De Jongh Raf , Kenis Gunter , Bosmans Eugene , Altamura Carlo , Maes Michael
Published: April 2003

Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations, total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the serum concentrations of albumin (Alb) and the β fraction were significantly lower in detoxified AWLD patients than in healthy volunteers. The percentage of the α2 fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated to increased serum IL-8. The percentage of the α1 and α2 fractions were significantly and positively related to serum IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD patients and that lower serum Zn may be causally related to lower serum Alb.
Cerebrospinal Cytokine Levels in Patients with Acute Depression
Authors: Levine J. , Barak Y. , Chengappa K.N.R. , Rapoport A. , Rebey M. , Barak V.
Published: April 2003

There is increasing evidence for an association between the alteration of cytokine concentrations in blood and the pathophysiology of depressive disorders. Studies in humans have not investigated CSF cytokine concentrations and their relationship to depressive disorders. This study reports on the association of the CSF concentration of proinflammatory cytokines, IL-1β, IL-6 and TNFα, and major depressive disorders. CSF samples were obtained from 13 hospitalized patients with acute unmedicated severe depression and were compared with 10 control subjects. Compared to the control group, the depressed patient group had higher CSF concentrations of IL-1β, lower IL-6 and no change in TNFα. A positive correlation was found between serum IL-1β and the severity of depression. These results indicate a unique profile for CSF proinflammatory cytokines in acute depression. These findings merit further investigation and if replicated may possibly offer immunological treatment options for depression.
Retrobulbar Optic Neuritis and Rhegmatogenous Retinal Detachment in a Fourteen-Year-Old Girl with Retinitis pigmentosa sine pigmento
Authors: Hatta Mitsuko , Hayasaka Seiji , Kato Tsuyoshi , Kadoi Chiharu
Published: April 2003

A 14-year-old girl complained of a sudden decrease in right visual acuity. The patient had night blindness, a mottled retina but no pigments, extinguished scotopic electroretinographic response, central scotoma in the right eye and rhegmatogenous retinal detachment. She had initially received laser photocoagulation around the retinal tear and then corticosteroid therapy, cryoretinopexy and segmental buckling. Her right visual acuity increased to 1.0. The association of retinitis pigmentosa sine pigmento, retrobulbar optic neuritis and rhegmatogenous retinal detachment, as demonstrated in our patient, may be uncommon.
Bilateral Angle Closure Glaucoma and Visual Loss Precipitated by Antidepressant and Antianxiety Agents in a Patient with Depression
Authors: Kadoi Chiharu , Hayasaka Seiji , Tsukamoto Eiki , Matsumoto Masayuki , Hayasaka Yoriko , Nagaki Yasunori
Published: April 2003

A 71-year-old woman with depression had been treated with an antidepressant (maprotiline) and antianxiety agents (clotiazepam and alprazolam). She had previously complained of ocular pain and blurred vision. However, thorough ocular examination was not performed at those times. On examination, visual acuity was no light perception OD and hand motion OS. Intraocular pressures were 33 mm Hg OU. Moderately dilated pupils, atrophic irises, shallow anterior chambers and closed angles were seen in both eyes. Despite treatment, her visual acuity decreased to no light perception bilaterally. Psychiatrists and ophthalmologists should be aware that antidepressants and antianxiety agents can precipitate angle closure glaucoma in susceptible eyes.
Ocular Findings in Aplastic Anemia
Authors: Mansour Ahmad M. , Salti Haytham I. , Han Dennis P. , Khoury Albert , Friedman Scott M. , Salem Ziad , Ibrahim Khaled , Bazerbachi Ali , Saghir Nagi
Published: April 2003

Objective: To analyze the ocular findings in aplastic anemia. Design: Eighteen patients with aplastic anemia were examined. Results: Ocular findings included cotton wool spots (38%), nerve fiber layer or preretinal hemorrhages (67%), vitreous hemorrhages (13%), a picture resembling central retinal vein occlusion (13%) and optic disk edema (6%). Preretinal hemorrhages were the presenting sign of aplastic anemia in 2 patients (13%). Conclusions: A blood profile is needed in patients with unexplained retinal hemorrhages. Patients with aplastic anemia need to avoid ocular massage and Valsalva maneuvers to decrease ocular morbidity.
Effects of Isoproterenolon the Orbicularis oculi andStapedius Muscles
Authors: Ishii Kosuke , Zhai Wei Gang , Akita Masumi
Published: April 2003

The effect of the β-adrenoceptor agonist, isoproterenol, on the orbicularis oculi and stapedius muscles was studied. Rats were injected with isoproterenol (5 mg/kg) every day. The animals were sacrificed after 1 and 2 weeks, and the orbicularis oculi muscle and stapedius muscle were removed. Muscle fibers were separated into single fibers, and cytochrome oxidase enzyme staining was applied with 1% MnCl2, DAB + H2O2. The density of cytochrome oxidase enzyme reaction products and the diameter of individual muscle fibers were analyzed by computer-assisted measurement. The administration of isoproterenol increased the activity of cytochrome oxidase as well as the diameter of muscle fibers in the orbicularis oculi muscle and stapedius muscle. It was suggested that these muscle fibers exhibited increases in functional activity after the administration. The results showed that the diameter and cytochrome oxidase enzyme activity of the orbicularis oculi and stapedius muscles increased. We conclude that isoproterenol induces hypertrophy of the orbicularis oculi and the stapedius muscle fibers, and promotes cytochrome oxidase enzyme activity.
Isepamicin Sulfate-Induced Sensorineural Hearing Loss in Patients with the 1555 A→G Mitochondrial Mutation
Authors: Usami Shin-ichi , Abe Satoko , Tono Tetsuya , Komune Shizuo , Kimberling William J. , Shinkawa Hideichi
Published: April 2003

A mitochondrial mutation at nucleotide 1555 has been reported to be susceptible to aminoglycoside antibiotics as well as one of the causes of nonsyndromic sensorineural hearing loss. We herewith report 2 cases bearing the 1555 A→G mitochondrial mutation who had hearing loss after short-term exposure to the new aminoglycoside antibiotic, isepamicin sulfate. Even when using aminoglycoside antibiotics with milder side effects, careful attention should be paid in applying them to patients with particular genetic backgrounds.
Results after Resection of Intraoral Cancer and Reconstruction with the Free Radial Forearm Flap
Authors: Stark Birgit , Nathanson Arthur , Hedén Per , Jernbeck Jan
Published: April 2003

Between 1989 and 1996, 47 patients with an intraoral squamous cell carcinoma underwent tumor resection and reconstruction with a free volar forearm flap. Tumor resection and neck dissection were performed by a head and neck surgeon and the free tissue transfer by a plastic surgeon. Preoperative radiation therapy was given to 44 of 47 patients and postoperative radiation therapy to 2. One other patient was not irradiated. There were 15 females and 32 males, with a mean age of 61 years. The primary site of the cancer was the tongue in 15 cases, the floor of the mouth in 15, the tonsil in 10, the bucca in 3 and the retromolar trigone in 4 cases. The flap was harvested from the left forearm in 34 and from the right in 13 patients. The mean operation time was 10 h (range 6–20) and the mean intraoperative bleeding was 486 ml (250–2,500). Forty-four of 46 flaps healed completely. Twelve revisions on 9 free flaps were performed between 6 h and 6 days postoperatively. Overall revisional surgery was done in 9 of 47 cases (19%). Two flaps could not be saved (4%). Infections/fistulas in the neck occurred in 11 of 46 cases (24%). Complete healing of the donor site occurred at a mean of 2.5 months (1–5). Nine patients developed complications at the donor site, 3 hematomas and 6 superficial infections (19%). Twenty-seven of 47 patients are still alive (57%). The mean survival time was 49 months (16–71).
Kimura’s Disease of the Intraparotid Lymph Nodes: Fine Needle Aspiration Biopsy Findings
Authors: Boccato Paolo , Mannarà Giacinto M. , Rinaldo Alessandra , La Rosa Filippo , Ferlito Alfio
Published: April 2003

A case of Kimura’s disease involving two intraparotid lymph nodes is described in a 16-year-old Caucasian boy presenting with a painless swelling of the right parotid gland. A preoperative diagnosis of Kimura’s disease was made on the basis of fine-needle aspiration biopsy (FNAB) and was confirmed by histological evaluation of the surgical specimen. FNAB is a safe and accurate procedure that can be used in the outpatient setting to enable a prompt preliminary diagnosis.
Microradiographic Study of Retrieved Craniofacial Osseointegrated Implants
Authors: Granström Gösta
Published: April 2003

In this study 18 screw-shaped extraoral osseointegrated implants retrieved from 10 patients were analyzed. The reasons for retrieval were: unexplained pain (n = 4); inability to cope with the implants (n = 2); fracture of the central screw (n = 2); skin penetration problems (n = 1), and trauma (n = 1). Retrieved implants were trephined with a border of surrounding bone, fixed, embedded in epon plastic, ground and processed for microradiography. The study group comprised 6 males and 4 females with a mean age of 53.4 (range 9–81) years. All implants were clinically stable at the time of removal, and the mean osseointegration time was 3 (range 1–5) years. Six implants were removed from the temporal bone, 5 from the frontal bone, and 7 from the maxilla. By microradiography, it was found that all retrieved implants were surrounded by a lamellar type of bone with haversian systems, vascular channels, osteocyte lacunae, and in some specimens regeneration and resorption areas. Bone metal contact was estimated to vary between 27 and 83%. Bone metal contact was lower in the frontal bone compared to the temporal bone or maxilla, and was further reduced after preoperative irradiation. Longer osseointegration time increased bone metal contact, as did increased age up to 60 years. It is concluded that extraoral osseointegrated implants in humans may integrate morphologically as well as clinically. By microradiography it was possible to define bone metal contact in the region of implant installation.
Glomangioma in the Nasal Cavity and Paranasal Sinuses
Authors: Nakagawa Takayuki , Takashima Tadayoshi , Tomiyama Kenta , Takeda Zenju
Published: April 2003

The glomangioma is a hyperplastic lesion of the glomus body. This uncommon tumor is seldom located in the nasal cavity or paranasal sinuses. We present what is to our knowledge the eleventh documented case of an intranasal glomangioma. The differential diagnosis of this lesion, its symptoms, pathogenesis and therapy are discussed. Complete excision is normally curative for this tumor.
Surgical Treatment of the Neck in Cancer of the Larynx
Authors: Ferlito Alfio , Silver Carl E. , Rinaldo Alessandra , Smith Richard V.
Published: April 2003

Current concepts in management of the clinically negative and clinically positive neck in laryngeal cancer are reviewed. Occult disease in the neck not detected by physical and radiographic examination may also be difficult to identify on routine histologic examination. Immunohistochemistry or molecular analysis may detect metastatic involvement not apparent by light microscopy. The surgeon should be aware of the relatively high incidence of micrometastases in patients with laryngeal cancer to establish optimal treatment approaches. Elective treatment of the neck is recommended for supraglottic tumors staged T2 or higher, and glottic or subglottic tumors staged T3 or higher.The neck may be treated electively by either surgery or irradiation, but irradiation is best reserved for cases where that modality is employed for the primary tumor. Elective neck dissection provides important information for prognostic purposes and therapeutic decisions, by establishing the presence, number, location and nature of occult lymph node metastases. The selective lateral neck dissection (levels II, III and IV), unilateral or bilateral, is the procedure of choice for elective treatment. Paratracheal nodes (level VI) should be dissected in cases of advanced glottic and subglottic cancer. Complete radical or functional neck dissections are excessive in extent, as levels I and V are almost never involved. Sentinel lymph node biopsy may fail to detect tumor on frozen section examination or may not reveal ‘skip’ metastases.The clinically involved neck is usually treated by complete radical or functional neck dissection of levels I through V. Selective neck dissection has been employed successfully in selected cases, particularly for N1 or occasionally N2 nodal involvement. The selective neck dissection can be extended to include structures at risk. More advanced disease has been treated in this manner often in association with adjuvant chemotherapy and/or irradiation. While the benefit of adjuvant treatment is difficult to assess, it appears most useful in cases with extranodal spread of disease, a factor associated with the worst prognosis.
The Effect of Interferon-γ and Tumor Necrosis Factor-α on the Expression of ICAM-1 and HLA-DR Molecules on Cells of a Human Germ Cell Neoplasm and Their Susceptibility to Lysis by Lymphokine-Activated Killer Cells
Authors: Eisenthal Avi , Marder Oleg , Maymon Batya , Misonzhnik Faina , Skornick Yehuda , Brazowski Eli , Czernobilsky Bernard , Walt Heinrich , Lifschitz-Mercer Beatriz
Published: April 2003

The ICAM-1 molecule plays a role in the interaction of NK cells with a variety of tumor cells, including carcinoma, melanoma and glioblastoma cells. In the present study, we analyzed the effect of IFN-γ and TNF-α on both the expression of HLA-DR and ICAM-1 molecules on HGCN (Germa-2), and on their susceptibility to lysis by LAK cells. Our results show that 1,000 U/ml IFN-γ induced a substantial increase in the expression of both ICAM-1 molecules and HLA-DR on the cell surface, while the effect of TNF-α on the expression of these molecules was substantially less prominent. When Germa-2 cells, previously exposed to 1,000 U/ml IFN-γ, were employed as target cells in a 4-hour 51Cr release assay, a statistically significant increase in the lysis by LAK cells was noted. These results show that in the presence of IFN-γ, Germa-2 tumor cells undergo modulation which affects both the expression of ICAM-1 and HLA-DR molecules as well as their susceptibility to lysis by LAK cells.
Effect of Ramiprilat or Captopril on Myocardial Infarct Size: Assessment in Canine Models of Ischemia Alone and Ischemia with Reperfusion
Authors: Black Shawn C. , Driscoll Edward M. , Lucchesi Benedict R.
Published: April 2003

Cardioprotective effects of the angiotensin-converting enzyme inhibitors captopril and ramiprilat were studied in two in vivo canine models of myocardial ischemic injury: 90 min of regional ischemia with 18 h reperfusion (protocol I) and 6 h of continuous ischemia without reperfusion (protocol II). In protocol I, neither ramiprilat (50 µg/kg) nor captopril (5 mg/kg + 0.25 mg/kg/h) reduced infarct size after 18 h of reperfusion (vs. controls). In protocol II, drugs were administered directly into both left anterior descending coronary artery and left circumflex branch. Compared to controls, continuous intracoronary administration of ramiprilat (40 ng/kg/min) or captopril (400 ng/kg/min) did not reduce infarct size. Thus neither captopril nor ramiprilat protected the heart from injury under conditions of ischemia with reperfusion or ischemia without reperfusion.
Studies on Pyrazinoylguanidine
Authors: Vesell Elliot S. , Beyer Jr. Karl H.
Published: April 2003

In a three-phase study, single oral doses of placebo, followed in 1 week by pyrazinoylguanidine (PZG; 900 mg), followed in 3 weeks by pyrazinoic acid (PZA; 300 mg) were given to 8 normal male subjects. Blood analyses performed 0, 2 and 4 h after administration of placebo or drug revealed that compared to mean 0 h values, PZG and also PZA, but not placebo, decreased mean values for serum glucose, insulin, C-peptide, triglycerides and free fatty acids. In all groups, serum potassium, urea, fibrinogen, high-density lipoprotein and low-density lipoprotein were unchanged. PZA, but not PZG, increased serum uric acid. PZG significantly reduced very-low-density lipoprotein whereas PZA only tended to do so. PZG was well tolerated and without any side effect, but in 7 of the 8 normal volunteers, PZA produced a variable vasomotor response over the blush area of the face and neck lasting from 30 min in 3 subjects to 4 h in 1 subject. Collectively, these results suggest generally similar metabolic responses of normal subjects to PZG and PZA after only a single oral dose of each. Previously, it was unrecognized that acute administration of PZG and PZA could produce such rapid metabolic changes.
Rasmussen’s Encephalitis: Neuroimaging Findings in 21 Patients with a Closer Look at the Basal Ganglia
Authors: Bhatjiwale Mohinish G. , Polkey Charles , Cox Tim C.S. , Dean Andrew , Deasy Neil
Published: April 2003

Rasmussen’s encephalitis usually presents in childhood. The clinical picture in Rasmussen’s disease is protean, and the findings from direct brain imaging help to explain the variations seen in this syndrome. The role and involvement of the basal ganglia in this condition is clarified by comparing the changes seen on computerised tomography and magnetic resonance imaging with the clinical details of 21 patients described in this retrospective study.
Diffuse Cerebral Vasospasm with Ischemia after Resection of a Cerebellopontine Angle Primitive Neuroectodermal Tumor in a Child
Authors: Lee Thomas T. , Ragheb John , Bruce Jocelyn C. , Altman Nolan , Morrison Glenn
Published: April 2003

This case report describes a 15-month-old female who developed diffuse cerebral vasospasm after resection of a cerebellopontine angle primitive neuroectodermal tumor. The patient developed an acute dense left hemiparesis 16 days postoperatively with partial right ptosis. Initial magnetic resonance imaging and diffusion study were unremarkable, though a magnetic resonance angiography 1 day later demonstrated severe intracranial vasospasm of both carotid and vertebral arteries. The vasospasm was confirmed with cerebral angiography. The patient progressed to bihemispheric infarcts with laminar necrosis despite combination therapy with anticoagulation, pharmacological hypertension, hypervolemia, and nimodipine. The clinical course, radiographic, and pathological findings are presented.
Down Syndrome and Craniovertebral Instability
Authors: Brockmeyer Douglas
Published: April 2003

The diagnosis and management of occipital-atlantal and atlantoaxial instability in Down syndrome patients is a challenging problem in pediatric spine surgery. To date, no systematic review of this topic has been presented on this confusing and sometimes contentious issue. This topic review will focus on the biomechanical and radiographic foundations for which treatment recommendations in Down syndrome patients are made. In addition, otolaryngologic and anesthetic considerations in Down syndrome are also discussed, as well as advances in surgery that have made the operative fusion of these patients easier and safer.
Value of Free Prostate-Specific Antigen (Hybritech Tandem-R) in Symptomatic Patients Consulting the Urologist
Authors: Hofer Christian , Sauerstein Peter , Wolter Christian , Scholz Michael , Hartung Rudolf , Breul Jürgen
Published: April 2003

Introduction: Prostate-specific antigen (PSA) is a widely used tumor marker in the detection and follow-up of adenocarcinoma of the prostate. Selection of candidates for prostate biopsies is hampered by the lack of specificity resulting in a large number of unnecessary biopsies. The intention of our study was to compare the percent free PSA (f-PSA; Hybritech Tandem-R) with total PSA and age-specific PSA reference values to evaluate the clinical benefit in detecting patients with prostate cancer (PC) in a selected group of patients consulting the urologist. The question was whether cutoff points are influenced by this selection of patients. Methods: A total of 188 patients, 114 with benign prostate hyperplasia (BPH) and 74 with PC were selected. It is a selected group of patients consulting the urologist. Diagnosis was confirmed in the BPH and PC groups by either ultrasound-guided biopsy or transurethral resection of the prostate or suprapubic adenomectomy or cystoprostatectomy. Total PSA (t-PSA) and f-PSA of all patients were measured before any manipulation by Tandem-R assay for f-PSA and Tandem-E assay for t-PSA (Hybritech). Mean values of age, prostate volume, t-PSA, f-PSA, percent f-PSA were compared in patients with BPH and PC by Mann-Whitney U test. The sensitivity and specificity of t-PSA and age-specific PSA were compared to the sensitivities and specificities of different cutoff points of percent f-PSA. Results: The mean value of t-PSA, f-PSA and percent f-PSA in patients with BPH (n = 114) and PC (n = 74) were statistically significantly different. At PSA levels between 4 and 10 ng/ml 19% of negative biopsies could be avoided by the use of percent f-PSA (cutoff point 25%). There was no additional benefit of age-specific PSA. At a PSA of <4 ng/ml 6 of 7 PCs could be diagnosed by percent f-PSA (cutoff point 25%), whereas only 1 patient would be diagnosed by age-specific PSA. Conclusion: Percent f-PSA seems to decrease the biopsy rate at PSA levels from 4 to 10 ng/ml without missing a relevant number of cancers and to increase the detection rate at PSA <4 ng/ml. Our data indicate that it might be necessary to choose high cutoff points (25%; Tandem-E and R assay, Hybritech) in a selected study population consulting the urologist with large glands and a high prevalence of disease. However, this situation is not comparable to testing of screening populations. No benefit of age-specific PSA could be observed in this study.
Sonographic Detection of a Foreign Body in the Urethra and Urinary Bladder
Authors: Barzilai Menashe , Cohen Inbal , Stein Avi
Published: April 2003

Reported herein is a 41-year-old male who presented for ultrasound due to two episodes of lower urinary tract infections within a period of 5 months. The sonographic examination revealed an elongated foreign body in the urethra extending into the urinary bladder. Self-insertion of foreign bodies into the urethra is usually done for erotic stimulation. However, foreign bodies can be inserted by children due to curiosity and by mentally retarded people, patients with psychiatric disorders as well as by intoxicated patients and in confusional states. Due to embarrassment, the patients seek medical help only when they are symptomatic and hence some of the foreign bodies are removed only several months after insertion. Detection might be either by plain abdominal films when the foreign bodies are radiopaque or by the use of contrast media. In the case presented by us, this was done by sonography. Endoscopic removal of these foreign bodies is considered the treatment of choice. Recurrent or chronic unexplained urinary tract infections should raise a high index of suspicion to the possible existence of a foreign body in the urethra and/or urinary bladder.
Prevalence of the G20210A Polymorphism in the 3'-Untranslated Region of the Prothrombin Gene in Different Human Populations
Authors: Franco R.F. , Santos S.E.B. , Elion J. , Tavella M.H. , Zago M.A.
Published: April 2003

Recently a novel polymorphism in the 3′-untranslated region of the prothrombin gene (a G to A transition at position 20210) was discovered, and an association with venous thrombosis and cardiovascular disease was found. The prevalence of the polymorphic allele in different human populations is unknown. We investigated the prevalence of the A 20210 allele of the prothrombin gene in 420 unrelated individuals (840 chromosomes) who belong to four different ethnic groups: Whites, African and Brazilian Blacks, Asians and Amerindians. PCR amplification followed by HindIII digestion was employed. The polymorphism was found in heterozygosity in 2 out of 120 Whites or a prevalence of 1.6% (allele frequency 0.8%), similar to that observed for other Caucasian populations. The A allele was absent among the other ethnic groups analyzed. Our data indicate that in non-Caucasians the prevalence of the 20210 G→A mutation in the prothrombin gene, if any, must be extremely low. The absence of this novel genetic risk factor for venous and arterial thrombotic disease among non-Caucasians may contribute to explaining geographical and ethnic differences in the risk of vascular disease.
Acute Promyelocytic Leukemia with Marrow Fibrosis at Initial Presentation: Possible Involvement of Transforming Growth Factor-β1
Authors: Mori Ako , Wada Hiroshi , Okada Masaya , Takatsuka Hiroyuki , Tamura Amane , Fujimori Yoshihiro , Okamoto Takahiro , Takemoto Yoshinobu , Kanamaru Akihisa , Kakishita Eizo
Published: April 2003

Although the occurrence of marrow fibrosis in acute myeloid leukemia has been described, there have been no reports of acute promyelocytic leukemia (APL) associated with marrow fibrosis. Here we describe an APL patient with severe marrow fibrosis at initial presentation. He had the typical manifestations of APL, except for marrow fibrosis. Complete remission was achieved by treatment with all-trans retinoic acid plus chemotherapy, and his marrow fibrosis gradually improved concomitantly with the decrease in leukemic cells. To clarify the mechanism of marrow fibrosis in this patient, we investigated the expression of genes for several cytokines promoting fibrosis by the reverse transcriptase polymerase chain reaction methods. An overexpression of transforming growth factor-β1 was noted in his leukemic cells at initial presentation, whereas no increase in expression was observed at the time of relapse when he no longer had marrow fibrosis. These findings suggest that overexpression of transforming growth factor-β1 was involved in the development of marrow fibrosis in this APL patient.
Reversal of Nephrotic Syndrome due to AA Amyloidosis in Psoriatic Patients on Long-Term Colchicine Treatment
Authors: Kagan Alexander , Husza’r Monica , Frumkin Azriel , Rapoport Jayson
Published: April 2003

A case of nephrotic syndrome due to AA amyloidosis in a young woman suffering from erythrodermic psoriasis and psoriatic arthropathy is reported. The nephrotic syndrome regressed completely during long-term (57 months) colchicine treatment. There are 39 case reports in the literature of psoriasis associated with amyloidosis. More than 85% of these patients had concomitant arthropathy. This suggests that arthritis may be an important factor in the appearance of amyloidosis. 59% of psoriatics with amyloidosis had renal failure and 56% of them died shortly after diagnosis of amyloidosis. These observations support the view that amyloidosis associated with psoriasis is an aggressive disease that may be fatal. However, the clinical course of our patient suggests that renal amyloidosis associated with psoriasis may be successfully treated by colchicine.
C-Type Natriuretic Peptide Inhibits Proliferation and Monocyte Chemoattractant Protein-1 Secretion in Cultured Human Mesangial Cells
Authors: Osawa Hiroshi , Yamabe Hideaki , Kaizuka Mitsuaki , Tamura Naoyuki , Tsunoda Satoru , Baba Yoshiko , Shirato Ken-ichi , Tateyama Fumiko , Okumura Ken
Published: April 2003

Background: Mesangial cell proliferation and matrix accumulation are hallmarks of various progressive glomerular diseases. We examined whether C-type natriuretic peptide (CNP) that is known to regulate the proliferation of vascular smooth muscle cells could modulate these pathological processes using human glomerular mesangial cells (GMCs) in culture. Methods: Proliferation of GMCs cultured with different concentrations of CNP-22 for 48 h was determined by a colorimetric assay using a tetrazorium salt. Monocyte chemoattractant protein-1 (MCP-1) and type IV collagen secretion into the culture media by GMCs in the presence or absence of CNP-22 were evaluated by ELISA. Expression of mRNA for natriuretic peptide receptor B (NPR-B), a specific receptor for CNP, was examined by reverse transcription polymerase chain reaction (RT-PCR). Results: CNP-22 (1–10 µM) inhibited serum-induced GMC growth in a dose-dependent manner. The amount of MCP-1 in the culture supernatant was increased approximately 2.4-fold by 5 µg/ml of lipopolysaccharide. This increase was inhibited by CNP-22 at 0.1–1 µM in a dose-dependent fashion. CNP-22 (10 µM) inhibited GMC type IV collagen secretion stimulated by 20 ng/ml of platelet-derived growth factor. Expression of NPR-B mRNA was confirmed in GMCs by RT-PCR. Conclusions: CNP suppresses GMC proliferation and MCP-1 and type IV collagen secretion by GMCs. It may have a therapeutic potential against human proliferative glomerular diseases, especially those with the involvement of monocytes.
Effects of Ionizing Radiation on Progressive Experimental Renal Disease: A Hemodynamic Approach
Authors: Teixeira Vicente P.C. , Segreto Helena R.C. , Boim Mirian A. , Razvickas Clara V. , Schor Nestor
Published: April 2003

In order to evaluate the progression of renal disease, Munich-Wistar rats were submitted to 5/6 nephrectomy and given whole-body x- or γ-irradiation with or without remnant kidney protection or were submitted only to remnant kidney irradiation. All groups received a single 6-Gy dose immediately after surgery. Whole-kidney function, glomerular hemodynamics, 24-hour proteinuria and histopathology were assessed 60 days after surgery and irradiation. The irradiated nephrectomized animals presented whole-kidney function parameters comparable to those of normal rats. In addition, they were less hypertensive and had higher hematocrit. They showed glomerular hyperfiltration and hypertension even greater than their respective nephrectomized controls. However, the interrelations among the glomerular filtration determinants were somewhat different in irradiated animals. Their 24-hour proteinuria was significantly lower and the sclerosis index and tubulointerstitial injury score were markedly smaller. Among irradiated animals, the worst sclerosis index was observed in those with a shielded remnant kidney and the best in those without protection of the remnant kidney. This led us to speculate about a possible influence of resident mesangial cells on the early events following renal mass ablation and on the maintenance of subsequent physiopathologic changes. Therefore, radiation undoubtedly provoked a beneficial change in the course of renal disease when the renal mass ablation model was employed. Many factors could have contributed to this favorable feature including lower levels of systemic arterial pressure, less increment in ΔP, diminished proteinuria, and maintenance of tubulointerstitial space integrity. Our data also suggest that development of glomerulosclerosis seems to be determined by events occurring immediately after injury.
Shiga Toxin-1 Regulation of Cytokine Production by Human Glomerular Epithelial Cells
Authors: Hughes Alisa K. , Stricklett Peter K. , Kohan Donald E.
Published: April 2003

Background/Aims: Inflammatory cytokines may enhance renal injury in post-diarrheal hemolytic uremic syndrome (Stx HUS) by enhancing the cytotoxic effect of Shiga toxins (Stx). The sources of inflammatory cytokines in Stx HUS are unclear. Since Stx-1 potently inhibits protein synthesis by glomerular epithelial cells (GEC) and increases cytokine release by renal epithelial cells, we examined Stx-1 regulation of cytokine production by human GEC. Methods: Stx-1 (and cycloheximide (CHX), another protein synthesis inhibitor) cytotoxicity, protein synthesis inhibition, and effect on interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) release and mRNA levels were determined. Results: Stx-1 alone had a modest stimulatory effect on inflammatory cytokine production by GEC that occurred at toxin concentrations ranging from minimal to 50% inhibition of protein synthesis. CHX, at concentrations that produced similar inhibition of protein synthesis, increased IL-1, IL-6, and TNF protein release and mRNA accumulation, but in a different time- and dose-dependent pattern than Stx. Lipopolysaccharide (LPS) did not change IL-1, but stimulated IL-6 and TNF production. LPS and Stx-1 combined stimulated production of all three cytokines to a greater extent than either toxin alone. Conclusion: These data indicate that: (1) Stx-1 alone modestly stimulates GEC inflammatory cytokine production; (2) LPS and Stx-1 combined can potently enhance GEC cytokine release, and (3) this action of Stx-1 may relate in part to inhibition of protein synthesis but cannot be fully attributed to this effect.
Epidemiology of Nephrolithiasis
Authors: Serio Angelo , Fraioli Antonio
Published: April 2003

The main purpose of the study is to acquire useful information on nephrolithiasis in Italy, given the recent increase in its prevalence. The analysis was based on data from sample surveys of the Italian population carried out in 1983 and 1993–1994 as well as on data obtained from medical records of patients treated at the ASTIF in Fiuggi. An increase in the prevalence of the disease from 11.7 to 17.2 out of 1,000 inhabitants has been observed over the last 10 years; most patients are men and elderly, and the highest frequency is in southern and the lowest in northern Italy. The results of the study confirm the hereditary predisposition, since nephrolithiasis is very common among patients’ parents (22.5%) and siblings (14.1%). The patients eat more meat than others and are often overweight or obese; the latter represent 18% of these patients and 11% of the general population.
Immunohematological Findings in Myelodysplastic Syndrome
Authors: Novaretti M.C.Z. , Sopelete C.R. , Velloso E.R.P. , Rosa M.F.C. , Dorlhiac-Llacer P.E. , Chamone D.A.F.
Published: April 2003

Background: Few immunohematological studies have been done in myelodysplastic syndrome (MDS). Methods: Twenty-nine MDS patients were retrospectively evaluated with a direct antiglobulin test (DAT), antibody screening, serum electrophoresis and immunoelectrophoresis. Clinical and laboratory studies (hemoglobin level, reticulocyte count, DHL, total and indirect bilirubin) were done simultaneously, as well as the French-American-British subtype and bone marrow biopsy findings. Results: Alloantibodies were demonstrated in 17 patients (58.6%), autoantibodies in 10 (34.4%) patients and cold agglutinin in 18 (62%) patients. DAT was mediated by only IgG in 8 patients (80%), by IgG and C3 in 1 patient (10%) and by IgG, IgA and C3 in 1 (10%) patient. No hemolytic disease occurred in patients with autoantibodies. Increased serum gammaglobulin was observed in 16 (54.4%) patients. There was no correlation between the incidence of allo-/autoantibodies and the gammaglobulin level (p = 0.937) and the presence of lymphocyte infiltrates in bone marrow biopsies (p = 0.156). No significant difference was observed when the incidence of autoantibodies and number of red blood cell transfusions were compared (p = 0.334). Patients with refractory anemia and refractory anemia with ringed sideroblasts subtypes had a higher incidence of allo-/autoantibodies than other MDS subtypes (p = 0.03). Conclusion: Patients with MDS, in particular refractory anemia and refractory anemia with ringed sideroblasts have a high incidence of allo- and autoantibodies, probably related to intrinsic immune disorder, without clinical or laboratory hemolysis.
Coagulopathy of Acute Promyelocytic Leukemia
Authors: Falanga Anna , Barbui Tiziano
Published: April 2003

Life-threatening bleeding is frequent in acute leukemias, particularly in acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia, characterized by the balanced reciprocal translocation between chromosomes 15 and 17. Laboratory assessments show profound hemostatic imbalance compatible with the clinical picture of disseminated intravascular coagulation. Activation of the coagulation system, hyperfibrinolysis and nonspecific proteases activity can be observed in this condition. An important pathogenetic role is attributed to the leukemic cell properties for activating hemostatic mechanisms. This review will summarize what is currently known about the coagulopathy of APL, the principal pathogenetic mechanisms, and the therapeutic tools for the management of this complication. Special attention will be devoted to the new therapy with all-trans retinoic acid, which has completely changed the natural history of APL and APL-related coagulopathy.
Cerebrovascular Brainstem Diseases with Isolated Cranial Nerve Palsies
Authors: Thömke Frank , Gutmann Ludwig , Stoeter Peter , Hopf Hanns Christian
Published: April 2003

There is a significant number of individual patients with cranial nerve palsies as the sole manifestation of MRI- and, less frequently, CT-documented small brainstem infarctions or hemorrhages. The 3rd and 6th nerves are most commonly involved and, less frequently, the 4th, 5th, 7th, and 8th nerves. An intra-axial basis for such lesions may be underestimated if the diagnosis is based solely on MRI. The electrophysiologic abnormalities indicating brainstem lesions may be independent of MRI-documented morphological lesions. This paper reviews the literature on cerebrovascular brainstem diseases manifesting as isolated cranial nerve palsies. It supports the concept that small pontine and mesencephalic infarctions are the main cause of non-traumatic cranial nerve palsies in the middle-aged and elderly population. Microvascular infarction of the respective extra-axial cranial nerve segments seem to be less important.
Squamous Cell Carcinomas of the Mandibular Alveolus: Analysis of Prognostic Factors
Authors: Shingaki Susumu , Nomura Tsutomu , Takada Masahito , Kobayashi Tadaharu , Suzuki Ichirou , Nakajima Tamio
Published: April 2003

Background: To assess the effect of clinicopathologic factors on local tumor control and survival in patients with mandibular alveolar carcinoma. Methods: Fifty patients with mandibular alveolar carcinoma treated surgically were included in this study. There were 3 patients with T1, 25 with T2, 5 with T3, and 17 with T4 disease. Clinical evidence of bone invasion was noted in 47 patients. A hemi- or segmental mandibulectomy was performed on 37 patients, whereas 10 patients had a marginal mandibulectomy. The impact of clinicopathologic variables on local tumor control and patient survival was assessed by univariate analysis. Variables included T and N stage, dental extraction, treatment modality, tumor differentiation, nodal status, surgical margin, and bone invasion. Results: Eleven patients (22%) develop recurrent disease, including 8 local recurrences, 1 neck, and 2 distant metastases. Overall, the 5-year actuarial rates of local control and disease-specific survival were 85 and 73%, respectively. Most local recurrences after surgical treatment were caused by inadequate resection margins. When resection margins were negative, the survival and local control rate were significantly better than when there were positive resection margins (survival, 91 vs. 11%; local control, 100 vs. 49%; p < 0.01). Neither T and N stages, clinical stage, tumor differentiation, dental extraction, bone invasion, extent of bone resection, nor treatment modality influenced outcome. Conclusions: The status of surgical margins was of major importance for the outcome of patients with gingival carcinoma of the mandible.
Effects of Rotational Stress of Different Duration on NK Cell Activity, Proinflammatory Cytokines, and POMC-Derived Peptides in Mice
Authors: Hale Kimberly D. , Ghanta Vithal K. , Gauthier Dorothy K. , Hiramoto Raymond N.
Published: April 2003

Previous studies have shown that the same stressor, depending on intensity, controllability, or duration, can have different effects on the immune system. The purpose of this study was to determine the effect of 10- and 20-min rotation on natural killer (NK) cell activity and also to establish if changes in body temperature, proinflammatory cytokine (IL-1β, IL-6, and TNF-α) levels, and proopiomelanocortin (POMC)-derived peptide (ACTH and β-endorphin) levels parallel the changes in NK cell activity in mice. We found that 10-min rotation significantly increased NK cell activity as compared to both the control (home cage) group and the 20-min-rotation group, while NK cell activity in the 20-min group was not significantly changed compared to the control group. Both 10 and 20 min of rotational stress decreased body temperature and induced significant changes in the proinflammatory cytokine and POMC-derived peptide levels as compared to the control group. The pattern of proinflammatory cytokine expression was quite different between the 10- and 20-min rotation groups. All three proinflammatory cytokines were expressed sequentially (at 0 h after rotation TNF-α, at 6 h IL-1β and IL-6, and at 24 h IL-6) in the 10-min rotation group, while the 20-min rotation group had a small increase in IL-1β (6.7 ± 1.8 pg/ml) at 0 h and increased levels of IL-6 at 6 and 24 h. There was a dissociation of ACTH and β-endorphin expression in both groups resulting in significantly more β-endorphin (p < 0.05) in the 10-min group at 6 h and significantly more ACTH (p < 0.04) in the 20-min group at 6 h. IL-1β and β-endorphin have both been shown to have a direct stimulatory effect on NK cell activity. Therefore, we suspect that the significant increase in both IL-1β and β-endorphin at 6 h in the 10-min-rotation group may be involved in the increased NK cell activity observed at 24 h in the 10-min-rotation group.