bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Radical Retropubic Prostatectomy in Patients with Locally Advanced Prostate Cancer: The Influence of Gleason Score 8–10
Authors: Sciarra Alessandro , Gentile Vincenzo , Voria Giuseppe , Mariotti Gianna , Seccareccia Fulvia , Pastore Antonio , Di Silverio Franco
Published: April 2003

Background: To define whether in locally advanced prostate cancer submitted to radical retropubic prostatectomy (RRP) the presence of a Gleason score 8–10 represents an index of high risk for progression and cancer-specific death. Methods: Finally, a total of 130 men with pathologically confirmed T3 cancer were included in this analysis. On the basis of the histological grade obtained at RRP, patients were divided into two groups: patients with a Gleason score 8–10 (group 1) and patients with a Gleason score <8 (group 2). Postoperative follow-up ranged from 24 to 120 months (median 60). After RRP no patients received additional treatments until a biochemical or clinical disease progression was found. Kaplan-Meier projections were used in each group. Results: After RRP, 41 patients (31.5%) had a Gleason score 8–10 tumor. The incidence of positive lymph nodes was significantly higher (p = 0.0030) in group 1 (36.6%) when compared with group 2 (12.3%). Significant differences between the two groups were also found with respect to seminal vesicle involvement (p = 0.0045) and positive surgical margins (p = 0.0040). The actuarial cumulative disease-specific survival for group 1 and group 2 was, respectively, 69 and 82% at 10 years. A Kaplan-Meier analysis demonstrated a 100% disease-specific survival, a 92% clinical progression-free survival and a 38% biochemical progression-free survival 10 years postoperatively if patients in group 1 had negative surgical margins and negative lymph nodes (48.8%). Conclusions: Our data indicate a significant association between Gleason score 8–10 and disease-specific survival, only if patients in group 1 are stratified on the basis of surgical margins and/or lymph node involvement.
Prevalence of Dementia in China
Authors: Liu Li , Guo Xiu-E , Zhou Yong-Qing , Xia Jie-Lai
Published: April 2003

To obtain prevalence estimates of dementia in China, an analysis of 17 studies published in Chinese from 1990–1999 was carried out. The prevalence rates for the population aged 60 years and older were 1.26% for Alzheimer’s disease (AD) and 0.74% for vascular dementia (VD). The prevalence of AD was 2.10% in women and 0.76% in men, while the prevalence of VD was 0.71 and 0.69%, respectively. The prevalence of AD among the three educational levels in our study (illiterate, primary school and high school) were 1.79, 0.45 and 0.15%, respectively, and those of VD were 0.26, 0.58 and 0.26%, respectively. Although the prevalence of AD (2.29%) was higher in urban than in rural areas (1.67%), the difference was not statistically significant. The difference between the prevalence of VD in urban (0.67%) and in rural areas (1.13%) was not significant either. The prevalence of AD increased with age, and gender was found to be associated with Alzheimer’s disease. The prevalence of VD also increased with age, but there was no association between VD and gender.
Attenuated Left Prefrontal Activation during a Verbal Fluency Task in Patients with Depression
Authors: Okada G. , Okamoto Y. , Morinobu S. , Yamawaki S. , Yokota N.
Published: April 2003

Functional neuroimaging studies on patients with depression have found abnormal activity in the left prefrontal and anterior cingulate cortex compared with healthy controls. Other studies have shown that these regions become active in healthy subjects during verbal fluency tasks, while patients with depression show impaired performance on such tasks. We used functional magnetic resonance imaging to investigate changes in cerebral blood oxygenation associated with a verbal fluency task in depressed patients and healthy volunteers. In contrast to 10 age- and sex-matched healthy control subjects who activated the left prefrontal cortex and the anterior cingulate cortex during word generation, 10 depressed subjects showed attenuated activation in the left prefrontal cortex and did not show significant activation in the anterior cingulate cortex. These findings suggest that impaired performance during verbal fluency task in depressed patients is associated with abnormal neural responses within these regions.
Clinical Evidence of the Endocrinological Influence of a Triphasic Oral Contraceptive Containing Norgestimate and Ethinyl Estradiol in Treating Women with Acne vulgaris
Authors: Sator P.-G. , Schmidt J.B. , Hönigsmann H.
Published: April 2003

Background and Objective: The aim of this study was to evaluate the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol in the treatment of women with acne vulgaris. Methods: 12 female patients were included and 10 completed the trial. Over a period of 6 months, efficacy was assessed by means of facial acne lesion counts, by an investigator’s global assessment, by patients’ self-assessments and by measuring epidermal moisture and skin surface lipids. In addition, a photo documentation was compiled and hormone levels were measured. Results: After 6 months of therapy, the number of acne counts improved. The success of treatment was rated positively both by the investigator and by all patients but one who did not report any changes. Skin surface lipids were significantly reduced while skin hydration showed no significant change. Testosterone and progesterone decreased, and sex-hormone-binding globulin increased, significantly. Conclusion: Our data show that an OC containing norgestimate and ethinyl estradiol is a good therapeutic option for women of fertile age suffering from mild to moderate acne vulgaris.
T-Cell Proliferative Responses following Sepsis in Neonatal Rats
Authors: Dallal Ousama , Ravindranath Thyyar M. , Choudhry Mashkoor A. , Kohn Annamarie , Muraskas Jonathan K. , Namak Shahla Y. , Alattar Mohammad H. , Sayeed Mohammed M.
Published: April 2003

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (103 CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20–25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis.
Mononuclear Cell Antigen Expression after Contact with One-Day Disposable Contact Lens Materials
Authors: Versura Piera , Iannelli Sandra , Stefoni Sergio , Caramazza Roberto
Published: April 2003

Purpose: To analyse the effects of 1-day disposable contact lens (CL) material on mononuclear cell activation antigens and adhesion molecules, in an in vitro model set up in order to simulate the first 2 h of wear. Methods: Etafilcon A and Hilafilcon A materials were analysed. Mononuclear cells, collected from peripheral blood samples of normal human donors, were placed in contact with the materials, both new and coated with artificial tear solution. As a control, Thermanox coverslips and a group with no material were included. Immunofluorescence reactions were carried out on cells, to study the distribution of activation (HLA-DR, CD25, CD69) and adhesion (CD11a, CD18, CD54) molecules; the flow cytometry technique was used to analyse cells. Results: Statistically significant results were demonstrated for the CD69 and all the 3 adhesion molecules. Artificial tear coating enhanced the mononuclear cell response. Conclusions: The daily mononuclear cell activation can lead, with time, to production of inflammatory mediators that may be responsible for discomfort or, at worst, intolerance and definitely to CL wear remittance.
Localization of Cell Apoptosis in the Opaque Portion of Anterior Polar Cataract and Anterior Capsulotomy Margin
Authors: Majima Kiyoyuki , Itonaga Kouichirou , Yamamoto Naoki , Marunouchi Tohru
Published: April 2003

Fas, Caspase 3 and single-stranded (ss) DNA are indicators of cell apoptosis. In the present study, Fas, Caspase 3 and ssDNA were found in the pyramidal opaque portions of anterior polar cataracts and the opaque portions of the anterior capsulotomy margin following intraocular lens (IOL) implantation. It is thus possible that apoptosis occurs in the lens epithelial cells in these regions, and this finding may be related to the fact that the pyramidal opaque portion of anterior polar cataracts and the opaque portions of the anterior capsulotomy margin following IOL implantation do not spread beyond a given range.
Insertion/Deletion Plasminogen Activator Inhibitor 1 and Insertion/Deletion Angiotensin-Converting Enzyme Gene Polymorphisms in Diabetic Retinopathy in Type 2 Diabetes
Authors: Globočnik-Petrovič Mojca , Hawlina Marko , Peterlin Borut , Petrovič Daniel
Published: April 2003

In an association study, the relationship between the insertion/deletion (I/D) plasminogen activator inhibitor 1 (PAI-1) gene polymorphism or the I/D angiotensin 1-converting enzyme (ACE) gene polymorphism and the development of diabetic retinopathy in patients with type 2 diabetes was investigated. One hundred and twenty-four subjects with type 2 diabetes and diabetic retinopathy were compared to 80 diabetic subjects without retinopathy with diabetes of a duration of more than 10 years. The PAI-1 gene distribution and ACE gene distribution in patients with diabetic retinopathy (4G4G 31.4%, 4G5G 46.8%, 5G5G 21.8%; DD 26.6%, ID 50.8%, II 22.6%) were not significantly different from those of diabetic subjects without retinopathy (4G4G 31.3%, 4G5G 50%, 5G5G 18.7%; DD 31.3%, ID 40%, II 28.7%). Neither the 4G/5G PAI-1 gene polymorphism nor the I/D ACE gene polymorphism contributed to the genetic susceptibility to diabetic retinopathy, either non-proliferative, proliferative or severe proliferative diabetic retinopathy, i.e. visual acuity of 0.1 or less in the better eye, in a group of Caucasian subjects with type 2 diabetes.
Evaluation of Lenticonus in Alport’s Syndrome: Quantitative Scheimpflug Analysis
Authors: Zhou Wei , Hirsch Marc , Junk Anna K. , Casper Daniel S. , Braunstein Richard , David Janice , Worgul Basil V.
Published: April 2003

Anterior lenticonus is an ocular abnormality that can occur in Alport’s syndrome. In this study, Scheimpflug slit imaging analyses were employed for quantitative and objective evaluation of lens changes associated with Alport’s syndrome. It was determined that while the apices of the lenticular protrusions are central in the vertical plane, they are nasally displaced in the horizontal meridian. The eccentricity and dimensions of the diameters and thicknesses of the conical aberration are highly correlated in both eyes. Lens thickness and anterior chamber depth do not differ between eyes. Densitometrically similar differences are apparent in the cortex and nuclear regions although evidence of overt opacification may or may not be present. The data strongly suggest that the physical parameters of the lenticonus are consistent with the constraints imposed by the pupil. Changes observed in the cornea and the vitreous may be associated with the syndrome.
Importance of Early Allergen Contact for the Development of a Sustained Immunoglobulin E Response in a Dog Model
Authors: Schiessl B. , Zemann B. , Hodgin-Pickart L.A. , de Weck A.L. , Griot-Wenk M. , Mayer P. , Nefzger M. , Schneider H. , Liehl E.
Published: April 2003

Background: Immunoglobulin E (IgE)-mediated allergies are postulated to require early allergen contact and sensitization for the full development of sustained IgE levels. Methods: Thirty-two Beagle dogs from seven litters selectively bred for their high IgE response were sensitized by subcutaneous injection of chicken ovalbumin (OVA), peanut extract and recombinant birch pollen allergen (Bet v 1). In half of the dogs from each litter, sensitization injections were started on the first day of life; the other half of the same litter was first sensitized at the age of 4 months. To evaluate whether early sensitization also predisposes the animals to IgE responses to other allergens later in life, we injected a recombinant timothy grass pollen allergen (Phl p 5) later on, at the age of 10–12 months. Allergen-specific serum IgE and IgG levels were evaluated with enzyme-linked immunosorbent assays. In addition, 21 dogs were challenged with aerosolized OVA to measure bronchoconstrictive changes in lung function. Results: Early sensitized dogs developed significantly higher OVA-specific serum IgE levels than late sensitized dogs, in contrast to the IgG levels, which were lower in these dogs (p < 0.001). The increase in specific serum IgE and IgG following boosting remained different between the two groups for over a year. Titers of specific serum IgE and IgG were also different after sensitization with a new allergen injected later in life for the first time. Dynamic pulmonary compliance and resistance, both parameters for bronchoconstriction induced by OVA aerosol challenge, were also significantly higher in early sensitized dogs (for both parameters, p < 0.01). Conclusions: Contact with an allergen early in life is decisive for the development of sustained IgE levels and the development of IgE responses to additional allergens encountered later in life. Allergen avoidance during early life may have some preventive effect on IgE-mediated allergy in dogs.
IGF-I and NT-3 Signaling Pathways in Developing Oligodendrocytes: Differential Regulation and Activation of Receptors and the Downstream Effector Akt
Authors: Ness Jennifer K. , Mitchell Nina E. , Wood Teresa L.
Published: April 2003

A previous study from our laboratory demonstrated differences in the ability of insulin-like growth factor-I (IGF-I) and neurotrophin-3 (NT-3) to promote survival of pro-oligodendroblasts (pro-OLs) against glutamate-mediated apoptosis. In the current study, we tested whether submaximal concentrations of NT-3 would maintain receptor tyrosine kinase TrkC activation and Akt phosphorylation and thus promote long-term survival of the pro-OL against glutamate. Our results demonstrate that NT-3 at any concentration sufficient to activate the TrkC receptor results in a transient phosphorylation of the receptor and of Akt due, in part, to downregulation of the Trk receptor. In contrast, even submaximal IGF-I concentrations maintain long-term Akt activation and prevent glutamate-mediated apoptosis in pro-OLs. In addition, we also present data showing that IGF-I and NT-3 differentially activate their receptors and Akt depending on the maturational stage of the oligodendrocyte.
Damage to the Choroid Plexus, Ependyma and Subependyma as a Consequence of Perinatal Hypoxia/Ischemia
Authors: Rothstein Raymond P. , Levison Steven W.
Published: April 2003

Cerebral hypoxia/ischemia (H/I) of the premature infant is a major cause of cerebral palsy and mental retardation. An important determinant of the ultimate outcome from this insult is the extent to which the stem cells and progenitors in the brain are affected. Irreversible injury to these cells will impair normal development of the infant’s brain and, hence, its function. In the present study, we examine early intervals after H/I to identify which cells in the periventricular region are most vulnerable. At 0 h of recovery from a perinatal H/I insult, the choroid plexus shows extensive necrotic damage. The adjacent ependymal and subependymal cells are also affected. Swelling of the ependymal and medial subependymal cells is observed; however, these cells rarely sustain permanent damage. By contrast, cells in the most lateral aspect of the subventricular zone (SVZ) show more delayed, but extensive apoptotic and hybrid cell deaths. Interestingly, activated macrophages/microglia are observed adjacent to the swollen ependymal cells as well as within the affected subependyma. We conclude that the choroid plexus is an especially vulnerable structure in the immature brain, whereas the ependymal and adjacent subependymal cells are relatively resistant to damage. As the medial aspect of the SVZ contains neural stem cells, we predict that neural stem cells will be especially resistant to perinatal H/I brain damage.
Positron Emission Tomographic Study of Post-Ischaemic-Hypoxic Amnesia
Authors: de Reuck J. , Vanwalleghem I. , Hemelsoet D. , de Weweire M. , Strijckmans K. , Lemahieu I.
Published: April 2003

Background: Despite extensive research, it still remains controversial as to what the precise location of the critical lesions underlying amnesia actually is. The amnesic syndrome is believed to be heterogeneous and due to several distinct functional deficits. Patients and Methods: Two patients, a 45-year-old woman and a 56-year-old man, with sudden cardiopulmonary arrest and successful resuscitation, were left with a clear amnesic syndrome as main neurological sequela. During their revalidation period, they underwent a positron emission tomographic (PET) examination, utilizing the 13NH3 bolus technique at rest and after intravenous acetazolamide administration. Results: Both PET studies showed more or less similar features with a decrease in regional cerebral blood flow (rCBF) in the frontal, temporal and parietal lobes. In addition, the rCBF was increased in both thalami of the 45-year-old woman and in the striata of the 56-year-old man. Acetazolamide vasoreactivity was most lost in the frontal lobes. Conclusions: In the present PET study, we demonstrated that destruction of the inhibitory pathways to the thalamus and basal ganglia by ischaemic-hypoxic frontal lesions could be one of the mechanisms leading to amnesia.
Spinal MRI Supporting Myelopathic Origin of Early Symptoms in Unsuspected Cobalamin Deficiency
Authors: Fritschi Jürg , Sturzenegger Matthias
Published: April 2003

We report two patients with subjectively progressive sensory symptoms and gait disturbance due to cobalamin deficiency, but only slight or absent abnormalities on neurological examination. In both patients, spinal MRI provided evidence for a myelopathic origin of the symptoms, disclosing characteristic T2 hyperintense signal alterations confined to the posterior columns of the cervical and thoracic spinal cord. The patients illustrate the early clinical presentation of subacute combined degeneration (SCD) with a sensory neuropathy starting with acroparesthesia and Lhermitte’s sign. Furthermore, the diagnostic value of spinal MRI for early diagnosis of SCD with characteristic findings is highlighted.
Spontaneous Spinal Epidural Hematoma in a 14-Year-Old Girl
Authors: Rosenberg Oded , Itshayek Eyal , Israel Zvi
Published: April 2003

Spontaneous spinal epidural hematoma is a rare cause of spinal cord compression in adults and even rarer in children. It is characterized by a sudden onset of acute back pain followed by acute neurological deterioration within a few hours. We report the case of a 14-year-old girl who presented with acute onset of back pain and progressive weakness of her lower limbs, to the point of being unable to stand or walk. CT imaging disclosed an acute thoracic spinal epidural hematoma. The hematoma was emergently evacuated. Postoperative examination disclosed no neurological deficit.
Wegener’s Granulomatosis with Parotid Gland Involvement and Pneumothorax
Authors: Bülbül Yılmaz , Özlü Tevfik , Öztuna Funda
Published: April 2003

Objective: Wegener’s granulomatosis is a systemic vasculitis characterized by necrotizing granulomatous lesions mostly involving the upper and lower respiratory tract. The disease rarely causes parotid gland involvement and pneumothorax. We report a case of Wegener’s granulomatosis involving parotid gland, and complicated with a pneumothorax. Clinical Presentation: A 45-year-old man admitted with a 3-week history of painful left parotid gland enlargement and hemoptysis. On physical examination a painful and hard mass was detected on the left pre-auricular area. Cervical CT revealed a 2 × 1.5 cm hypodense lesion mimicking an abscess on the left parotid gland. Chest radiograph and thorax CT demonstrated nodular and cavitating opacities on the right and left upper zones. There were numerous erythrocytes in urine sediment. The drained pus material from the parotid abscess demonstrated only gram-positive cocci (Staphylococcus aureus). Two weeks treatment with teicoplanin resulted in no improvement. Meanwhile, parotid gland biopsy revealed necrotizing granulomatous inflammation. There was a sixfold increase in serum cANCA levels. With the diagnosis of Wegener’s granulomatosis, cyclophosphamide and prednisolone were initiated. However, 1 month later, pneumothorax developed as a complication of rupture of a cavitary lesion. Conclusion: Parotid gland swelling may be the initial presenting symptom of Wegener’s granulomatosis. It can be confused with infectious or malignant diseases of the gland, and the lung involvement may be complicated with pneumothorax.
A Comparative Study of Samarium-153-Ethylenediaminetetramethylene Phosphonic Acid with Pamidronate Disodium in the Treatment of Patients with Painful Metastatic Bone Cancer
Authors: Wang Rong Fu , Zhang Chun Li , Zhu Shou Li , Zhu Mei
Published: April 2003

Objective: To assess the therapeutic efficacy and toxicity of samarium-153-ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) and pamidronate disodium in patients with painful metastatic bone cancer. Subjects and Methods: Eighteen patients with histopathologically confirmed malignancy and multifocal bone metastases were randomized into two equal groups of 9 patients each. Group A was treated with 153Sm-EDTMP, while group B was treated with pamidronate disodium. The pain score for each patient was recorded before and after therapy using visual analogue scales that graded both the intensity and frequency of the bone pain. Therapeutic response was classified as inefficient, mild, effective and excellent. Results: Pain score in each group prior to therapy was more than 6. In group A, 2 (22.2%) and 7 (77.8%) cases showed mild and effective response, respectively. The therapeutic efficacy of 153Sm-EDTMP was adjudged to be 77.8%. Transient myelosuppression was generally mild and reversible with white blood cells and platelets recovering after 6 weeks. In group B, palliative response in 4 cases (44.4%) was inefficient, in 1 case (11.1%) mild, in 3 cases (33.3%) effective and in 1 case (11.1%) excellent, with a therapeutic efficacy of 44.4% for pamidronate disodium. No hematological toxicity was noted. Conclusion: The data showed that the therapeutic efficacy of 153Sm-EDTPM was higher than that of pamidronate disodium (for pain relief maintained more than 3 weeks) and its incidence of blood toxicity was also higher than that of pamidronate disodium.
Acoustic Properties of Vocally Disruptive Behaviors in the Nursing Home
Authors: Cohen-Mansfield Jiska , Werner Perla , Hammerschmidt Kurt , Newman John D.
Published: April 2003

Background: Disruptive vocalizations are among the most common behavior problems in the nursing home. However, their acoustic properties have not been previously investigated. Objective: This paper examines the acoustic properties of disruptive vocalizations and attempts to link them to resident and verbalization characteristics. Methods: This study characterizes the sounds emitted by 26 nursing home residents who manifested disruptive vocalizations. Verbalizations were audiotaped and then used in a sonographic evaluation and an acoustic analysis. Results: Vocalizations of verbally agitated nursing home residents were characterized by their relatively short duration. Consistent positive correlations were found between seemingly disturbing types of vocalizations, such as yelling and howling, and higher levels of several parameters of the fundamental frequency. A similar positive correlation was also found between acoustic parameters and medical disease indicators. With the exception of the length of stream of utterances, the indicators did not differentiate between types of dementia. Conclusions: Because of the large number of comparisons undertaken, it is difficult to conclude which associations between acoustic properties and resident or vocalization characteristics are attributable to real underlying trends and which are due to chance and error. Consistencies that deserve further research pertain to the perceptions of the types of vocalizations the person tends to emit and to the physical health of the person.
Postnatal Maternal Separation Elevates the Expression of the Postsynaptic Protein Kinase C Substrate RC3, but Not Presynaptic GAP-43, in the Developing Rat Hippocampus
Authors: McNamara Robert K. , Huot Rebecca L. , Lenox Robert H. , Plotsky Paul M.
Published: April 2003

We have shown that exposure of rats to neonatal handling/maternal separation results in mossy fiber axon hypoplasia in field CA3 of the hippocampus. To better understand the molecular basis of this neuroanatomical alteration, the present study examined three developmentally regulated protein kinase C substrate mRNAs that are highly expressed in hippocampal granule cells during mossy fiber outgrowth: GAP-43, a presynaptic substrate implicated in axonal outgrowth, RC3 (neurogranin), a postsynaptic substrate implicated in calmodulin signaling, and MARCKS-like protein (MLP), which binds calmodulin and filamentous actin in neurons and glial cells. mRNA expression was examined by quantitative in situ hybridization in the developing [postnatal day 7 (P7), P13, P21, and P90] hippocampus (CA1, CA3, granule cells) in Long-Evans hooded rats: (1) reared under normal animal facility (AFR) conditions, (2) subjected to brief (15 min/day, HMS15), or (3) subjected to moderate (180 min/day) handling/maternal separation (HMS180) on P2–14. RC3 mRNA expression was consistently elevated in all of the hippocampal cell fields in HMS180 rats relative to HMS15 and/or AFR rats over postnatal development, but did not differ from HMS15 rats in adulthood. In contrast, neither GAP-43 mRNA nor MLP mRNA expression differed among AFR, HMS15, or HMS180 rats at any postnatal time point. Elevations in RC3 expression would be predicted to perturb calcium-calmodulin signaling that may, in turn, impair the formation and/or maintenance of mossy fiber-CA3 synapses during postnatal development.
Immunocytological Studies of L-MAG Expression Regulation during Myelination of Embryonic Brain Cell Cocultures
Authors: Keita Mahamane , Magy Laurent , Heape Anthony , Richard Laurence , Piaser Martine , Vallat Jean-Michel
Published: April 2003

The myelin-associated glycoprotein (MAG) possesses two isoforms, known as S-MAG and L-MAG. We followed the expression and localization of L-MAG in comparison to myelin basic protein (MBP) during myelination in dissociated embryonic rat brain cell cocultures. Using immunofluorescence microscopy, we observed L-MAG and MBP in oligodendrocyte (OL) cell bodies and processes before and at the onset of myelination. At advanced stages of myelination, L-MAG immunostaining decreased, and subsequently disappeared from OL soma and myelinated internodes, whereas MBP immunoreactivity decreased only in the OL soma. These results are consistent with biochemical studies and provide the first clear demonstration of a transient expression of L-MAG during the early stages of myelination in vitro, providing further evidence that L-MAG plays a role during this period.
An Extensive Search for Autoantibodies to Myelin Basic Protein in Cerebrospinal Fluid of Non-Multiple-Sclerosis Patients: Implications for the Pathogenesis of Multiple Sclerosis
Authors: Warren Kenneth G. , Catz Ingrid
Published: April 2003

Inflammation of multiple sclerosis (MS) brain and spinal cord tissue consists of macrophages, T lymphocytes and cytokines as well as B lymphocytes and immunoglobulins (IgGs). IgG can be detected in high concentrations in both central nervous system tissue and cerebrospinal fluid (CSF). Using a sensitive radioimmunoassay (RIA), autoantibodies to myelin basic protein (anti-MBP) can be detected in the CSF of 90–95% of MS patients with active disease. The purpose of the present report was to determine whether these same autoantibodies can be reliably detected in non-MS patients. Between 1978 and 1998, CSF was collected from 1,968 control non-MS patients with psychiatric, inflammatory and noninflammatory neurological diseases as well as nonneurological systemic diseases, and anti-MBP were measured by the same RIA used to detect anti-MBP in MS CSF. Anti-MBP were undetectable in 98% of CSF samples from non-MS controls. In the remaining 2% of control samples, CSF IgGs capable of binding to MBP in vitro were unpredictably detected. This latter group included 1% of patients with miscellaneous diseases such as encephalomyelitis, 5 siblings with familial spastic paraparesis, rare patients with strokes, Wernicke-Korsakoff’s syndrome, inherited leukodystrophy, motor neuron disease and some patients with miscellaneous spinal cord diseases. An additional 1% of patients included a group with neurological symptoms suggestive of early or predisseminated MS. The high prevalence of free and/or bound anti-MBP in the CSF of MS patients and the rare and unpredictable occurrence in the CSF of non-MS patients suggest that autoimmunity to MBP may be operative in the demyelination of MS. Molecular clones of anti-MBP with specificity towards variable surface or cryptic MBP epitopes in vivo may determine whether or not they are involved in the demyelinating process, and this variability may also be present within the MS population. Potential mechanisms of anti-MBP-mediated demyelination in MS patients are discussed.
Natural Killer Cell Frequency and Function in Yorkshire Pigs Selectively Bred for High or Low Antibody and Cell-Mediated Immune Response
Authors: Raymond Claudine , Wilkie Bruce , Mallard Bonnie , Quinton Margaret
Published: April 2003

Porcine NK cells are small to medium-size lymphocytes having a variety of functions that may include the regulation of immune response. Thus frequency and function of NK cells were examined in generations 6 and 8 (G6, G8) of pigs selectively bred for high (H) and low (L) antibody and cell-mediated immune response (CMIR). Using the monoclonal antibody 5C6 as a pan NK phenotype marker and target cell binding and lysis as assays of function, it was found that H and L immune response pigs had high and low NK cell frequency, respectively, at G6 and G8. Function of NK cells differed by line, with the control (unselected) pigs being higher (with respect to target cell binding) or similar (with respect to lytic activity) to H which were higher than the L line pigs. Frequency of NK cells after primary immunization was in significant negative correlation with antibody after secondary immunization with hen egg white lysozyme (HEWL). Therefore, simultaneous selection for antibody and CMIR altered the frequency and function of NK cells in pigs with C ≧ H > L.
Immunomodulatory Effects of IL-12 in Relation to the Pineal Endocrine Function in Metastatic Cancer Patients
Authors: Lissoni Paolo , Rovelli Franco , Giani Luisa , Fumagalli Luca , Mandalà Mario
Published: April 2003

In addition to IL-2, IL-12 would constitute one of the most promising cytokines in the treatment of human neoplasms. IL-2 has been proven to induce in vitro and in vivo several evident changes in the secretion of cytokines and various other immunoinflammatory substances. In contrast, very litte data are available about the immune effects of IL-12 in humans. The present study was carried out to investigate the in vivo immunoinflammatory effects of IL-12 by analyzing the secretions of neopterin, soluble IL-2 receptor (SIL-2R), tumor necrosis factor α (TNF), IL-2 and IL-6 in relation to the neuroendocrine function of the pineal gland, which is one of the most important organs involved in neuroimmunomodulation. Pineal endocrine function was investigated by evaluating the whole daily urinary excretion of the main catabolite of its hormone melatonin, 6-sulfatoxymelatonin (6-MTS). The study was performed on metastatic renal cell cancer patients. Each course of IL-12 consisted of 1.25 µg/kg b.w. subcutaneously in the morning once a week for 3 consecutive weeks. The study evaluated 10 IL-12 courses. Mean serum levels of neopterin, SIL-2R and TNF significantly increased in response to IL-12, whereas no significant change occurred in IL-6 and IL-2 mean concentrations. Finally, 6-MTS urinary excretion was significantly reduced by IL-12 injection, particularly during the dark phase of the day. This preliminary study would suggest that IL-12 may induce important changes in the in vivo immunoinflammatory response. Moreover, IL-12 administration would suppress pineal endocrine activity, thus confirming its previously suggested involvement in the neuroimmunomodulatory processes. Because of the fundamental role of the pineal gland in neuroimmunomodulation, IL-12-induced immune variations could depend at least in part on its action at central neuroendocrine sites.
CSF-1 (M-CSF) Enhances the Inflammatory Response of Fibronectin-Primed Macrophages: Pathways Involved in Activation of the Cytokine Network
Authors: Kremlev Sergey G. , Chapoval Andrei I. , Evans Robert
Published: April 2003

We have previously reported that the priming of thioglycollate-elicited peritoneal macrophages (PMφ), as a representative population of mononuclear phagocytes (MNP), by macrophage-colony-stimulating factor (M-CSF or CSF-1) rendered these cells more susceptible to secondary stimulation by extracellular matrix (ECM) proteins, in particular fibronectin (FN), and that at least two β1 integrins, VLA 4 (α4β1 or CD49d) and VLA 5 (α5β1 or CD49e), regulate IL-6 gene expression when PMφ come into contact with FN. In this report, we focused our attention on resident PMφ, as a more mature/differentiated MNP subpopulation. By using granulocyte-macrophage colony-stimulating factor (GM-CSF)- and IL-6-knockout (null) mice, we demonstrated that the cooperative effect between CSF-1 and FN in IL-6 release was a result of a sequential stimulation of the GM-CSF, but not the TNF-α, gene via interaction with VLA 5. We also showed that regardless of the presence or absence of CSF-1 or FN, IL-6 inhibits GM-CSF and TNF-α gene expression in an autocrine manner. The observed effects were specific because CSF-1 enhanced VLA 5 expression and blocking FN-treated resident PMφ in vitro with VLA 5 monoclonal antibodies inhibited the IL-6 response. We found that treatment of resident PMφ with the protein kinase C inhibitor, staurosporine, and the activator, phorbol myristate acetate (PMA), resulted in marked modulation of either FN- or FN/CSF-1-induced cytokine release. An increased level of VLA 5 expression was observed in PMA-treated resident PMφ. We concluded that in inflammatory processes, CSF-1 drives a number of pathways involved in the regulation of the expression of several genes and renders MNP highly susceptible to stimulation by ECM proteins that transform the MNP into secretory inflammatory cells.
Expression of Fas and Fas Ligand and Apoptosis in Tumor-Associated Lymphocytes and in Tumor Cells from Malignant Pleural Effusions
Authors: Sikora Jan , Dworacki Grzegorz , Żeromski Jan
Published: April 2003

The CD95 (APO-1/Fas)-Fas ligand (FasL) system is an important mediator of antitumor T cell cytotoxicity. The aim of the current study was to assess its significance in human cancer. Malignant effusions were selected as an environment allowing direct cell-to-cell contact in a fluid phase. Malignant pleural effusions collected from 23 patients with metastatic carcinoma of the bronchus, ovary, stomach or breast were examined by means of flow cytometry. The expression of Fas and FasL, probed with the appropriate antibodies, apoptosis of tumor cells and the characteristics of tumor-associated lymphocytes (TAL) were determined by TUNEL reaction in malignant and nonmalignant (control) effusions. All malignant cells had partially or completely lost the expression of CD95 and expressed an elevated level of FasL. In contrast, TAL obtained from malignant pleural effusions demonstrated a marked decrease in the expression of surface FasL and an increase in surface-bound Fas. The percentage of apoptotic malignant cells was significantly decreased, as compared to TAL and lymphocytes from nonmalignant pleural effusions. There were also differences in the expression of Fas and FasL among mononuclear cells from malignant and nonmalignant pleural effusions. The ability of TAL from malignant pleural effusions to induce apoptosis of K562 cells was diminished, as compared to peripheral blood lymphocytes. Taken together, these data suggest that tumor cells in the microenvironment of malignant pleural effusions can evade immune attack by downregulation of the CD95 receptor and by killing lymphocytes through the expression of FasL. These results confirm earlier reports which showed that lymphocytes from a tumor microenvironment appear to have a depressed cytotoxic action.
Immunocytochemical Detection of Estrogen Receptor-α in the Female Rabbit Forebrain: Topography and Regulation by Estradiol
Authors: Caba Mario , Beyer Carlos , González-Mariscal Gabriela , Morrell Joan I.
Published: April 2003

Two antibodies (H222 and Zymed) directed towards different sites of the estrogen receptor-α (ERα) were used for the following objectives: (1) to map the ERα in the forebrain of ovariectomized (ovx) rabbits by immunocytochemistry and (2) to determine the effect of endogenous (intact non-pregnant animals) and exogenous (ovx, estrogen-treated animals) estradiol (E2) on the population of ERα in the forebrain. Similar results were obtained with both antibodies used: dense aggregations of ERα-immunoreactive (IR) neurons were found in the infundibular nucleus (IN), the medial preoptic area (POA), the bed nucleus of the stria terminalis (BNST), and some nuclei of the amygdala. By contrast, no ERα-IR neurons were present in the ventromedial hypothalamic nucleus (VMN), but a dense aggregation of ERα-IR neurons occurred lateral to it in nucleus X. Numerous ERα-IR neurons were observed in the paraventricular hypothalamic nucleus, but not in the supraoptic or suprachiasmatic nuclei. The hippocampus proper lacked ERα-IR neurons, but the ventral subiculum in the hippocampal formation had a dense group of such cells. Intact non-pregnant rabbits showed less ERα-IR neurons in all regions tested than ovx animals. This difference was particularly clear in the medial POA, amygdala and BNST, while the IN showed only a marginal decrease. The dorsal, but much less the ventral, part of nucleus X also showed a decrease in the number of ERα-IR neurons compared with ovx animals. E2 benzoate (5 µg/day for 5 days) reduced even further the number of ERα-IR neurons in all regions except in a circumscribed area of the IN and the ventral part of nucleus X. These results show the existence of both sensitive and insensitive neurons to the down-regulatory effect of E2 on the presence of ERα. Sensitive neurons are located in the telencephalon, POA and several hypothalamic nuclei (PVN), while insensitive neurons are mainly restricted to the IN and the ventral part of nucleus X in the basal hypothalamus.
Micromolar A and B Blood Group Active Trisaccharides Abolish Human Complement Haemolytic Activity Assayed by Erythrocytes
Authors: Bakács Tibor , Szabó Miklós , Varga László , Mushens Rosey , Mehrishi Jitendra N. , Lutz Hans U. , Merry Tony H. , Tusnády Gábor
Published: April 2003

Background: At present, there is really no satisfactory treatment of severe haemolytic transfusion reactions involving the ABO system other than the use of steroids that at best are palliative in their effects. In contrast, the use of micromolar concentrations of A or B blood group active trisaccharides that are inexpensive and readily available may prevent lysis by generating soluble immune complexes (ICs) that consume complement. The purpose of this study was to determine the total lytic activity of human serum and to estimate the extent to which trisaccharides can exhaust this capacity. Methods: We measured complement consumption by (ICs) formed between anti-blood group antibodies and A or B blood group active sugars on erythrocytes (solid phase) or soluble components carrying trisaccharides (fluid phase) in AB serum. A direct complement-mediated lysis (DCL) assay measured the solid-phase reaction and an indirect complement consumption assay (CCA) allowed determination of the fluid-phase reaction. In CCA, the residual lytic activity of AB serum was measured following preincubation with various ICs. Results: Based on over 4000 data points a new mathematical model of complement consumption was formulated. Its predictions deviated by less than 6% in DCL and 9% in CCA when compared with the experimentally accessible data. The new model describes the dynamics of complement consumption including the soluble phase of the reaction. Conclusions: The mathematical model extrapolation predicts that: (1) in undiluted human serum up to 40% of the physiological erythrocyte concentration could be lysed (when antibodies did not limit lysis); and (2) a 40 µM (or less) concentration of blood group active trisaccharides per patient is sufficient to block the haemolytic complement activity.
Effect of Glucose Polymer on the Intercellular Junctions of Cultured Human Peritoneal Mesothelial Cells
Authors: Ito Takafumi , Yorioka Noriaki , Kyuden Yasufumi , Asakimori Yukiteru , Kiribayashi Kei , Ogawa Takahiko , Kohno Nobuoki
Published: April 2003

Background: Glucose polymer is an active osmotic agent that is increasingly used as an alternative to glucose in peritoneal dialysis fluids. It was recently reported that the duration of peritoneal dialysis can be extended by using glucose polymer in patients with poor ultrafiltration. We previously demonstrated that high glucose levels damage the intercellular junctions of cultured human peritoneal mesothelial cells (HPMC), but little is known about the influence of glucose polymer. Therefore, we investigated the effects of glucose polymer on the intercellular junctions of HPMC. Methods: HPMC were isolated, cultured, and identified according to the modified method of Stylianou. M199 medium was supplemented with peritoneal dialysis solutions containing 7.5% glucose polymer or 1.5, 2.5, and 4.25% glucose. After 6 h, cell viability was assessed, intercellular junction proteins were examined by immunofluorescence techniques, and the concentration of transforming growth factor-β1 in the culture supernatant was determined. Results: Glucose significantly suppressed cell viability and significantly increased transforming growth factor-β1 production when compared with control or glucose polymer cultures. Peritoneal dialysis solutions containing 4.25% glucose caused the detachment of HPMC. Immunofluorescence of intercellular junction proteins (tight junctions: ZO-1, occludin, and claudin-1; adherens junctions: β-catenin) became weak and uneven after culture with glucose. On the other hand, glucose polymer caused little change in the immunofluorescence of these proteins when compared with control cultures. Conclusions: Glucose polymer seems to be less toxic to HPMC than glucose itself, suggesting that the glucose polymer may be better for peritoneal dialysis.
‘Clonal Pluralization of the Self’: A New Form of Delusional Misidentification Syndrome
Authors: Vörös Viktor , Tényi Tamás , Simon Mária , Trixler Mátyás
Published: April 2003

The authors present a patient with paranoid schizophrenia, who has the delusion that he exists in plural numbers. The patient declares these doubles to be both psychologically and physically completely identical to him, and he believes ‘them’ to be in fact women. In connection with the case, the authors discuss the phenomena of reduplicative paramnesia and clonal pluralization, and they suggest introducing the psychopathological term ‘clonal pluralization of the self’ for the reported phenomenon.
Histological and Ultrastructural Study of the Effect of Chemotherapy with 5-Fluorouracil on Normal Liver of Wistar Rats
Authors: Zafiriou G. , Grekou A. , Stravoravdi P. , Natsis K. , Barich A.
Published: April 2003

Background: In this study, we analysed the histopathological and ultrastructural effects of systemic chemotherapy with 5-fluorouracil (5-FU) on the liver of healthy rats. Methods: Twenty inbred Wistar rats were used as controls and another 20 rats received a bolus infusion, via the inferior vena cava, of 375 mg/m2 5-FU. The animals of each group were sacrificed 16 h, 3 days or 1, 2, 3 and 6 months postoperatively. Results: Histologically, in one rat 16 h after 5-FU administration, we observed only a small necrotic focus of hepatocytes. Ultrastructurally, a mild vacuolization of cytoplasm, a decrease in mitochondria and an increase in lysosomes were observed. These abnormalities were restored 1 month later. Conclusion: Our results confirm that the particular dose, route and duration of 5-FU administration do not cause hepatotoxic morphological changes in the liver of healthy Wistar rats.