bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological Significance of the Interleukin 1 Receptor Accessory Protein
Authors: Layé Sophie , Liège Stéphane , Li Kang-Sheng , Moze Elisabeth , Neveu Pierre J.
Published: April 2003

Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal-transducing component of the IL-1 receptor type I. The recent availability of IL-1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP. Animals were injected intraperitoneally with rat recombinant IL-1β (200 ng/mouse), lipopolysaccharide (LPS, 5 µg/mouse), or subjected to 1-hour restraint stress. Neuroendocrine and immune parameters were measured 2 h after IL-1 or LPS injection or just after restraint. In wild-type controls, IL-1 and LPS activated the hypothalamic-pituitary-adrenal axis and increased plasma IL-6. In KO mice, the plasma levels of corticosterone and IL-6 increased after LPS, but not after rat recombinant IL-1β. The LPS-induced depression of the lymphoproliferation was similar in wild-type and KO mice. Finally, the 1-hour restraint was able to increase the plasma levels of corticosterone in KO mice. These results show that IL-1RAcP is essential for physiological activities of peripheral IL-1, as it was previously demonstrated for those of brain IL-1. However, using IL-1RAcP KO mice, we were unable to demonstrate a specific role of endogenous IL-1 during LPS-induced inflammation. Moreover, stress-induced activation of the hypothalamic-pituitary-adrenal axis may occur in the absence of the IL-1-transducing receptor, IL-1RAcP.
Adenomyomatosis of the Papilla of Vater: A Case Illustrating Diagnostic Difficulties
Authors: Kayahara Masato , Ohta Tetsuo , Kitagawa Hiroshisa , Miwa Koichi , Urabe Takeshi , Murata Takashi
Published: April 2003

Aim: To describe the extremely rare case of an adenomyoma of the papilla of Vater. Case Report: A 42-year-old woman was hospitalized for epigastralgia and high fever. The clinical presentation and endoscopic, biochemical, and radiologic findings led to the diagnostic impression of a dysfunction of the papilla of Vater. The patient was treated successfully by laparotomy and duodenotomy, incorporating cholangiomanometry and cholangiography. Intraoperative frozen-section examination of a transduodenal papillectomy specimen led to the diagnosis of adenomyomatosis of the papilla. The patient is doing well 38 months postoperatively. Conclusion: Such a combined approach to intraoperative diagnosis was important to avoid excessive surgery for a benign periampullary disease.
Expression of Nitric Oxide Synthase during the Development of RCS Rat Retinas
Authors: Sharma Rajesh K. , Warfvinge Karin , Ehinger Berndt
Published: April 2003

Nitric oxide (NO) has been reported to be both neurodestructive and neuroprotective in the central nervous system and could possibly play an important role in neurodegenerative disorders. On the assumption that NO synthesis may influence degenerative processes in the retina, we have examined the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive cells in developing Royal College of Surgeons (RCS) rat retinas, which is an animal model for retinal degeneration. An antibody against constitutive neuronal NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days 3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days 3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas but were distinctly seen in the PN 7 retina along with a plexus in the inner plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of the plexus in the inner plexiform layer could be seen at PN 10, which became more distinct at PN 14. The immunoreactive cells were detected also in the oldest retina examined, which was PN 281 in the case of RCS rats. In both groups, certain amacrine cells, certain bipolar cells and certain horizontal cells were found to be immunoreactive. In conclusion, the developmental timetable of the NOS immunoreactivity was identical in the normal and the RCS rat retinas. The NOS-immunoreactive cells persisted in the RCS retinas even when the retina had degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot be ruled out from this study. We conclude that the chronological and qualitative development of the constitutive neuronal NOS immunoreactivity is normal in RCS rat retinas.
Intraocular Pressure Response to Selective Laser Trabeculoplasty in the Treatment of Primary Open-Angle Glaucoma
Authors: Gračner Tomaž
Published: April 2003

Purpose: To evaluate the intraocular pressure (IOP) response to selective laser trabeculoplasty (SLT) in the treatment of uncontrolled primary open-angle glaucoma (POAG) in a prospective clinical study. SLT is a new laser procedure that selectively targets trabecular meshwork (TM) cells without coagulative damage to the TM. Methods: 50 eyes with uncontrolled POAG were treated with a frequency-doubled, Q-switched Nd:YAG laser (532 nm). A total of approximately 50 nonoverlapping spots were placed over 180° of the TM at energy levels ranging from 0.40 to 0.92 mJ/pulse. After SLT, the eyes were maintained with the identical hypotensive medical therapy as that before treatment. IOP was estimated before and 1 day, 7 days, 1 month, 3 months and 6 months after treatment. Results: The mean pretreatment IOP was 22.48 mm Hg (SD 1.84). At the end of 1 month of follow-up IOP was reduced with a mean of 4.86 mm Hg (SD 2.38) or 21.6%; after 3 months, IOP was reduced with a mean of 5.66 mm Hg (SD 2.40) or 25.2%; at the end of 6 months of follow-up, IOP was reduced with a mean of 5.06 mm Hg (SD 2.37) or 22.5%. Conclusions: SLT is an effective method for lowering IOP in the treatment of POAG.
Bullous Pemphigoid in a Patient Treated with UVA-1 Phototherapy for Disseminated Morphea
Authors: Sacher C. , König C. , Scharffetter-Kochanek K. , Krieg T. , Hunzelmann N.
Published: April 2003

Bullous pemphigoid is an autoimmune disease of the skin characterized by the production of antibodies directed at structures of the basement membrane zone (BMZ) leading to subepidermal blisters. Several causative triggers have been described in the literature, among them UV light. Here, we report on a 73-year-old Caucasian female with disseminated morphea who developed blisters on her extremities after receiving whole-body UVA-1 phototherapy. The initial differential diagnosis of a phototoxic versus photoallergic reaction was ruled out as the lesions continued to spread after discontinuation of phototherapy. Histological and direct immunofluorescence examination showing a subepidermal blister and linear IgG deposits along the BMZ along with detection of circulating anti-BMZ antibodies led to the diagnosis of bullous pemphigoid. Immunosuppressive therapy resulted in regression of all blisters. After ruling out other possible causes, such as neoplasias or drugs, we conclude that UVA-1 has to be regarded as the most likely trigger of the disease.
NC/Nga Mice: A Mouse Model for Atopic Dermatitis
Authors: Suto Hajime , Matsuda Hiroshi , Mitsuishi Koichi , Hira Kayako , Uchida Takafumi , Unno Tetsushi , Ogawa Hideoki , Ra Chisei
Published: April 2003

Atopic dermatitis (AD) is a common pruritic disease that occurs primarily in infancy and childhood. AD is characterized by itching and the patient having an individual or family history of atopic diseases. Although AD is also frequently associated with elevated serum IgE levels and with common environmental factors contributing to its pathogenesis, the etiology of AD is still unknown. We examined NC/Nga mice (NC mice) that showed AD-like skin lesions with aging as a possible mouse model for AD. NC mice were maintained under conventional (Conv) or specific pathogen-free (SPF) conditions. Clinical symptoms, serum IgE levels and histopathology of the skin were compared between these 2 groups, and we explored their application as a model of human AD. It was found that the skin lesions of inbred NC mice were clinically and histologically very similar to human AD when the mice were raised under Conv conditions, but not under SPF conditions, and we assumed that some kinds of environmental factors might trigger AD-like signs and symptoms in NC mice. To further investigate the pathophysiology and treatment of AD, a suitable animal model is absolutely required, and NC mice are very useful for this purpose.
Controlled Comparison of the Efficacy and Safety of Cetirizine 10 mg o.d. and Fexofenadine 120 mg o.d. in Reducing Symptoms of Seasonal Allergic Rhinitis
Authors: Horak F. , Stübner P. , Zieglmayer R. , Kavina A. , De Vos C. , Burtin B. , Donnelly F.
Published: April 2003

Background: The efficacy, onset and duration of action and safety of cetirizine 10 mg o.d., fexofenadine 120 mg o.d., and placebo were compared in this investigator-blinded, crossover study involving the use of the Vienna Challenge Chamber. Methods: 40 volunteers with seasonal allergic rhinitis were exposed to a controlled grass pollen concentration for 6 h on 2 consecutive days. Subjective symptoms and objective measurements were recorded during the allergen exposure periods. Results: Both active medications were significantly more effective than placebo and had a comparable onset of action in alleviating the symptoms of seasonal allergic rhinitis. The efficacy of both active drugs was comparable for the first 4 h after administration of the drugs on day 1 and day 2. However from 22 to 24 h after the first dose cetirizine was significantly superior to fexofenadine for the major symptom complex score and for sneezing. Concerning the total symptom complex score at day 2 fexofenadine could not reach superiority to placebo. No serious adverse events were reported. Conclusions: Cetirizine and fexofenadine were significantly better than placebo, also in reducing the symptom of nasal congestion. However cetirizine appears to have a longer duration of action than fexofenadine.
A Comparison of FcεRI-Mediated RANTES Release from Human Platelets between Allergic Patients and Healthy Individuals
Authors: Hasegawa Shunji , Tashiro Norimichi , Matsubara Tomoyo , Furukawa Susumu , Ra Chisei
Published: April 2003

Background: Recently some studies have suggested that human platelets may play an important role in allergic inflammation through the high affinity IgE receptor (FcΕRI), the low affinity IgE receptor (FcΕRII/CD23) and the low affinity IgG receptor (FcγRIIA/CD32) expressed on the cell surface. We reported that human platelets via the FcΕRI induced the release of the chemical mediator serotonin and the chemokine RANTES (regulated upon activation, normal T expressed and presumably secreted), but the biological implication of human platelets in type I allergy has not yet been understood clearly. Methods: We compared the levels of RANTES release from platelets obtained from allergic patients and healthy individuals, stimulated with monoclonal antibody (Ab) to human FcΕRI α-chain, or human myeloma IgE and anti-human IgE Ab. Results: We confirmed that the level of RANTES release from platelets of allergic patients stimulated with human IgE and anti-human IgE was significantly higher than that of healthy individuals. Conclusions: We demonstrated that the surface expression levels of FcΕRI on the platelets from allergic patients and healthy individuals were not significantly different, but that the platelets of allergic patients were more activated by the IgE-FcΕRI pathway than those of healthy individuals. Taken together, these results suggest a novel and important role for human platelets in perpetuating allergic inflammation through the IgE and FcΕRI.
Atopic Eczema/Dermatitis Syndrome and Malassezia
Authors: Scheynius Annika , Johansson Catharina , Buentke Eva , Zargari Arezou , Tengvall Linder Maria
Published: April 2003

Atopic dermatitis is a chronic multifactorial inflammatory skin disease, which has had a marked increase in prevalence during the last decades. Recently, a new nomenclature was recommended where the term ‘atopic eczema/dermatitis syndrome’ (AEDS) should be used to reflect the heterogeneity in this group of patients and where those patients without measurable IgE reactivity should be classified as either ‘nonallergic AEDS’ or ‘non-IgE-associated allergic AEDS’. For nearly 20 years it has been discussed whether the opportunistic yeast Malassezia, previously designated Pityrosporum, is a contributing factor to AEDS. Today there are several reports that demonstrate specific serum IgE or positive skin prick test and/or atopy patch test reactions to Malassezia in patients with AEDS. Several IgE-binding components have been identified in extracts of Malassezia ranging in molecular mass between 10 and 100 kD. The genes for nine Malassezia allergens with molecular weights ranging from 14 to 36 kD have hitherto been identified and cloned. Six of them are now produced by recombinant techniques and used in diagnostic tests. At present the genus Malassezia is subdivided into seven different species, which all have been isolated from human skin. The respective contribution of different Malassezia spp. to AEDS and in what proportion they share allergens remains to be clarified. We summarize here data that Malassezia can play a role in eliciting and maintaining eczema in patients with AEDS.
Inhibition of Cytomegalovirus in vitro and in vivo by the Experimental Immunosuppressive Agent Leflunomide
Authors: Waldman W. James , Knight Deborah A. , Blinder Leonard , Shen JiKun , Lurain Nell S. , Miller Daniel M. , Sedmak Daniel D. , Williams James W. , Chong Anita S.-F.
Published: April 2003

Despite progress in antiviral chemotherapy, cytomegalovirus (CMV) remains a major cause of morbidity and mortality among pharmacologically immunosuppressed transplant recipients, frequently engaging the clinician in a struggle to balance graft preservation with control of CMV disease. Leflunomide, an inhibitor of protein kinase activity and pyrimidine synthesis, is an experimental immunosuppressive agent effective against acute and chronic rejection in animal models. Herein we summarize our recent studies demonstrating that leflunomide inhibits the production of multiple clinical CMV isolates (including multi-drug-resistant virus) in both human fibroblasts and endothelial cells. In contrast to all other anti-CMV drugs currently in use, leflunomide does not inhibit viral DNA synthesis, but rather appears to interfere with virion assembly. Finally, preliminary studies in a rat model suggest that this agent reduces viral load in vivo. These findings imply that leflunomide, an effective immunosuppressive agent, shows potential to concurrently attenuate a major complication of immunosuppression, CMV disease, by a novel mechanism of antiviral activity.
Simultaneous Blockade of Two Glutamate Receptor Subtypes (NMDA and AMPA) Results in Stressor-Specific Inhibition of Prolactin and Corticotropin Release
Authors: Zelena Dóra , Makara Gábor B. , Jezova Daniela
Published: April 2003

Many neurons express simultaneously two or more isotypes of glutamate receptors, so that pharmacological modulation of more than one receptor may be necessary to reveal the role of glutamate in mediating physiological processes. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic hormone (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-801, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rats were pretreated for 4–5 days and then exposed to stressful stimulation. Basal hormone levels were not affected by the antagonists. In male rats, combined, but not separate blockade of NMDA and AMPA/kainate subtypes of glutamate receptors prevented the rise in plasma PRL in response to footshock stress. In female rats, footshock-induced PRL release was inhibited even by separate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobilization or ether stress. Simultaneous blockade of NMDA and AMPA receptor subtypes resulted in a mild inhibition of immobilization-induced ACTH release without any effect on ACTH response to footshock or ether stress. The data suggest that involvement of glutamatergic pathways in neuroendocrine response during stress is selective for discrete stress stimuli and stress hormones. In addition a concerted action of glutamate on both NMDA and non-NMDA receptor subtypes is involved in the control of PRL release during footshock stress.
Neuropeptide Y Innervation and Neuropeptide-Y-Y1-Receptor-Expressing Neurons in the Paraventricular Hypothalamic Nucleus of the Mouse
Authors: Broberger Christian , Visser Theo J. , Kuhar Michael J. , Hökfelt Tomas
Published: April 2003

The paraventricular hypothalamic nucleus (PVH) serves as integrator and link between the neuroendocrine and autonomic nervous systems. Neuropeptide-Y (NPY)-producing neurons in the arcuate nucleus project to the PVH, where neurons expressing NPY Y1 receptor (Y1R) have been demonstrated. This projection has been suggested to be involved in the regulation of parameters related to energy metabolism, e.g. food intake and thermoregulation. The present study aimed at characterizing this pathway and chemically defining Y1R-expressing neurons by means of immunohistochemistry. The densely distributed NPY-immunoreactive (ir) terminals in the PVH co-stained for agouti gene-related protein (AGRP) mainly in the medial parvocellular regions, indicating an origin in the arcuate nucleus. This was in contrast to noradrenergic/adrenergic terminals in the PVH, which were less frequently seen to contain NPY-like immunoreactivity. Furthermore, AGRP-ir terminals were seen forming abundant close appositions on Y1R-ir cell bodies. Double staining revealed co-existence of Y1R-like immunoreactivity and immunoreactivities for thyrotropin-releasing hormone (TRH) and, to a minor extent, cocaine- and amphetamine-regulated transcript peptide in parvocellular neurons. No Y1R-like immunoreactivity was noted in parvocellular neurons expressing corticotropin-releasing hormone or in magnocellular neurons expressing vasopressin or oxytocin. The present results suggest that the arcuatoparaventricular NPY projection targets the TRH neurons preferentially via the Y1R, whereas the NPYergic regulation of corticotropinergic and magnocellular neurons may be relayed through other subtypes of NPY receptors. This study further defines the link between NPY-induced feeding and the hypothalamus-pituitary-thyroid axis.
Minimal Change Nephrotic Syndrome Developing during Postoperative Interferon-Beta Therapy for Malignant Melanoma
Authors: Nakao Kazushi , Sugiyama Hitoshi , Makino Eiichi , Matsuura Hironori , Ohmoto Akiko , Sugimoto Taro , Ichikawa Haruo , Wada Jun , Yamasaki Yasushi , Makino Hirofumi
Published: April 2003

A 64-year-old man presented with proteinuria during postoperative interferon (IFN)-β therapy against malignant melanoma. Renal pathologic findings were consistent with minimal change nephrotic syndrome (MCNS) showing extensive foot process effacement of visceral glomerular epithelial cells (podocyte). Nephrotic range proteinuria gradually regressed after stoppage of local injection of IFN-β without glucocorticoid treatment. To our knowledge this is the first report that demonstrates histological abnormalities of the glomerulus associated with postoperative IFN-β therapy for the malignant melanoma.
Low Arylsulphatase A Activity in the Development of Psychiatric Disorders
Authors: Mihaljević-Peleš Alma , Jakovljević Miro , Miličević Željko , Kračun† Ivica
Published: April 2003

Previous studies have suggested that arylsulphatase A (ASA) deficiency may be present in psychiatric patients. A number of patients with low ASA activity and various neuropsychiatric symptoms have been observed. Metachromatic leucodystrophy (MLD) is a disease caused by deficiency of the enzyme ASA. Clinically, adult MLD may present as a schizophrenia-like psychosis, deterioration of cognitive functions, personality changes, depression and dementia. However, there are individuals with low ASA activity without clinical symptoms of MLD. This state is described as ASA pseudodeficiency. It remains controversial whether low ASA activity predisposes to or influences the development of psychiatric symptoms. Relatively little attention has been paid to the role of neurodegenerative processes in the pathophysiology of psychiatric disorders. The hypothesis underlying this work is that there is a subclass of mentally ill patients whose psychiatric problems are at least partly caused by an abnormal ASA. The purpose of this particular study was to determine whether an abnormal ASA could be detected in schizoprenic, major depressed and demented patients and control subjects. There were 66 schizophrenic, 59 major depressed and 61 demented patients. The control group consisted of 102 healthy volunteers. Leucocyte ASA activity was determined from blood samples, using p-nitrocatechol sulphate as substrate. Our results show that low ASA activity is more frequently found in psychiatric patients than in control subjects. Our findings indicate that clinical types of major depression and schizophrenia could be connected with low ASA activity. The presence of a decreased ASA activity points to the conclusion that an enzyme deficit entails vulnerability to psychiatric disorders.
Animal Study on the Effects of Catalin on Aftercataract and Posterior Capsule Opacification
Authors: Biswas Nihar R. , Mongre Praveen K. , Das Gopal K. , Sen Seema , Angra Surinder K. , Vajpayee Rasik B.
Published: April 2003

Purpose: To find out the role of Catalin in the prevention of posterior capsular opacification (PCO), we undertook this experimental study in rabbits. Methods: Twenty rabbits (10 for the Catalin group and 10 for the placebo group) were operated on for extracapsular clear lens extraction in an aseptic environment. In all cases, capsulorrhexis of 8 mm diameter was carried out. Both the test drug and placebo were given at a dose of 4 times/day from the first postoperative day for 8 weeks. Common drugs in both groups were topical corticosteroid, antibiotic and cycloplegic drops. Periodic slitlamp examinations and photographic documentations were carried out to find any evidence of aftercataract. At the end ot 8 weeks, histopathological examination was carried out to document any evidence of aftercataract. Result: Overall, evidence of aftercataract was seen in 6 rabbits in the control group and 3 in the Catalin group; the degree of PCO was higher in the placebo group. Conclusion: We found that Catalin played some role in preventing PCO.
Age-Related Nuclear Cataract: A Lens Transport Problem
Authors: Truscott Roger J.W.
Published: April 2003

Age-related nuclear cataract is a major cause of blindness. It is characterised by opacification and colouration in the centre of the lens and is accompanied by extensive protein oxidation. The reason for the onset of nuclear cataract is not known, but it is proposed here that the underlying cause is the development, with age, of a barrier to the transport of metabolites within the lens. Such a barrier may result in an increase in the half-lives of reactive molecules, such as UV filters, thus promoting posttranslational modification of proteins in the nucleus and may also act to prevent an adequate flux of antioxidants from reaching the lens interior and, as a consequence, allow oxidation of nuclear components. Further, this oxidation may take place even if the lens outer cortex and epithelium remain perfectly functional.
TIMP-1 Production by Human Scleral Fibroblast Decreases in Response to Cyclic Mechanical Stretching
Authors: Yamaoka Akihiro , Matsuo Toshihiko , Shiraga Fumio , Ohtsuki Hiroshi
Published: April 2003

Purpose: The effect of mechanical stretching was examined on cultured scleral fibroblasts of the human eye in order to observe changes in their production of TIMP (tissue inhibitor of metalloproteinase)-1, MMP (matrix metalloproteinase)-1 and -2 in response to physiological strain. Methods: Human scleral fibroblasts were cultured from scleral tissue resected during foveal translocation surgery. The fibroblasts in near confluency were exposed to mechanical stretching of the bottom of a 6-cm Petri dish at the maximum magnitude of 4500 microstrain and at a cycle of 30 s for 72 h. TIMP-1, MMP-1 and MMP-2 levels in the medium following 24, 48 and 72 h of cyclic stretching were measured by enzyme immunoassay. Results: The growth of scleral fibroblasts during the 72-hour period of stretching did not show a significant difference from that of non-stretched control fibroblasts. Scleral fibroblasts in the stretched group produced a significantly smaller amount of TIMP-1 at 72 h after stretching, compared with nonstretched control (p = 0.0353, Student t-test). The levels of MMP-1 and MMP-2 produced by scleral fibroblasts were not significantly different between the stretched group and nonstretched group. Conclusion: The production of TIMP-1 by human scleral fibroblasts was suppressed by cyclic mechanical stretching. Mechanical strain would be one factor to regulate the homeostasis of extracellular matrix in the sclera.
Image-Guided, Frameless Stereotactic Sectioning of the Corpus callosum in Children with Intractable Epilepsy
Authors: Hodaie Mojgan , Musharbash Awni , Otsubo Hiroshi , Snead III O. Carter , Chitoku Shiro , Ochi Ayako , Holowka Stephanie , Hoffman Harold J. , Rutka James T.
Published: April 2003

Corpus callosotomy is an effective neurosurgical procedure for children with intractable atonic or drop attack seizures. While this procedure has not changed significantly over the past three decades, some technical issues remain to be resolved. These include the intraoperative determination of the extent of the callosotomy, the need to stage the procedure, as well as side of approach of craniotomy. We report our 8-year experience with corpus callosotomy using a frameless stereotactic image-guided system (ISG Viewing Wand®). Seventeen children with atonic seizures underwent sectioning of the corpus callosum. The mean patient age was 10.5 years. Six children underwent complete callosotomy while 11 underwent resection of the anterior two-thirds. MRI 3D reconstruction of the sagittal sinus and draining cerebral veins was undertaken in all cases. The side of the craniotomy was determined on the basis of favorability of the draining veins with respect to the extent of the callosotomy. The extent of the callosotomy was determined by intraoperative feedback using the ISG Viewing Wand®. Nine of 11 patients in the partial callosotomy group and 4 of 6 patients in the complete callosotomy group showed significant improvement in atonic seizures. We conclude that the use of frameless stereotaxy can function as an important adjunct in the planning and conduction of successful sectioning of the corpus callosum in children with intractable seizures.
Pituitary Adenomas: The Effect of Gamma Knife Radiosurgery on Tumor Growth and Endocrinopathies
Authors: Pan L. , Zhang N. , Wang E. , Wang B. , Xu W.
Published: April 2003

Seventy-three patients have been treated with Gamma Knife radiosurgery (GKR) for pituitary adenomas. 12 had undergone surgery prior to GKR. Three had had previous radiation therapy. The prescription dose administered to the tumor margin ranged from 9 to 35 Gy. 65 patients were followed up for an average of 29 months. A slight expansion of tumor volume occurred in 3 cases. Otherwise, the tumor volume remained unchanged or decreased in the remainder. Endocrine changes were present in all except 3 cases. GKR was followed by a speedy decrease in raised serum hormone levels in the case of both growth hormone (GH)and adrenocortico-tropic hormone (ACTH). In 3 patients there was some visual deterioration associated with a slight increase in tumor volume. In 2 cases, the tumors were removed surgically. Some preliminary conclusions may be drawn. The dose required to correct an endocrinopathy may be higher than that required for control of tumor growth. The recommended prescription dose for endocrine-active adenomas may be more than 30 Gy. While clinical improvement may be noted in patients with raised serum prolactin levels (PRL), normalization of the endocrinopathy may be less readily achieved than in the case of raised GH and ACTH levels. Gamma Knife radiosurgery as a primary treatment of pituitary adenomas can be safe and effective.
Monozygotic twins of opposite sex
Authors: Wachtel S.S. , Somkuti S.G. , Schinfeld J.S.
Published: April 2003

Although discordant karyotypes are known in identical twins, cases involving differences in sex phenotype are rare. We studied identical twins with the 46,XY karyotype – a male with mixed gonadal dysgenesis and a female with “pure” gonadal dysgenesis. The testis-determining SRY gene was present in DNA from both twins but no mutations were detected in the SRY conserved motif. Monozygosity was indicated by short tandem repeat polymorphism analysis. These observations could be attributed to (i) mutation and mosaicism involving “downstream” sex-determining loci, (ii) variable penetrance of genes such as DSS/NR0B1, duplication of which can disrupt the male-determining pathway, or (iii) occurrence of cryptic 45,X gonadal cell lines.
Exploitation of an Ancient Escape Circuit by an Avian Predator: Relationships between Taxon-Specific Prey Escape Circuits and the Sensitivity to Visual Cues from the Predator
Authors: Jabłoński P.G. , Strausfeld N.J.
Published: April 2003

The painted redstart Myioborus pictus uses visual displays to flush, pursue, and then capture an abundance of brachyceran Diptera that are equipped with giant fiber escape circuits. This paper investigates the relationships between features of the giant fiber system, the structure of visual stimuli produced by redstarts and their effectiveness in eliciting escape reactions by flies. The results show that dipterous taxa having large-diameter giant fibers extending short distances from the brain to motor neurons involved in escape are flushed at greater distances than taxa with longer and small-diameter giant fibers. The results of behavioral tests show the importance of angular acceleration of expanding image edges on the compound eye in eliciting escape responses. Lateral motion of stimulus profile edges as well as structured visual profiles additionally contribute to the sensitivity of one or more neural systems that trigger escape. Retinal subtense and angular velocity are known to trigger physiological responses in fly giant fiber circuits, but the contributions of edge length and lateral motion in a looming stimulus suggest that escape pathways might also receive inputs from circuits that are tuned to different types of motion. The present results suggest that these several properties of escape pathways have contributed to the evolution of foraging displays and plumage patterns in flush-pursuing birds.
Further Modification to Soft Drinks to Minimise Erosion
Authors: Hughes J.A. , Jandt K. D. , Baker N. , Parker D. , Newcombe R.G. , Eisenburger M. , Addy M.
Published: April 2003

Soft drinks have been successfully modified to reduce enamel erosion. The aim of this study was to further modify an original low erosive blackcurrant drink product by the addition of a gum, to manipulate more favourably other drink parameters. The study was a single–blind, randomised four treatment crossover design involving 12 healthy volunteers. During 10 working–day study periods, subjects wore enamel samples in the mid palatal region of a removable appliance. Specimens were taped to expose a 2–mm enamel window. The drinks under test were: (1) Orange juice, (2) Original blackcurrant drink, (3) Water, and (4) Experimental blackcurrant drink. Drinks were imbibed at 250–ml volumes 4 times a day during appliance wearing from 09.00 to 17.00. Appliances were removed at lunchtime. Measurements of specimens were made at baseline, 2, 5 and 10 days using a profilometer. One 5–day and one 10–day specimen from each subject during each treatment were ultrasonicated. Significant differences, in erosion between drinks, were seen at days 5 and 10. Comparisons of preselected pairs of drinks of interest showed significantly reduced erosion by the two blackcurrant drinks compared to orange juice with no significant differences from water. The original blackcurrant drink produced significantly less erosion than the experimental drink. Ultrasonication removed enamel from the Orange juice specimens but very little from those exposed to water and the two blackcurrant drinks. Extrapolating the effects of both blackcurrant drinks suggested that alone they should not cause significant clinical erosion in a lifetime’s intake of 1 litre per day.
The Beneficial Toxicity Paradox of Antimicrobials in Leg Ulcer Healing Impaired by a Polymicrobial Flora: A Proof-of-Concept Study
Authors: Fumal I. , Braham C. , Paquet P. , Piérard-Franchimont C. , Piérard G.E.
Published: April 2003

Background: Some of the views contrasting the beneficial and toxic effects of antimicrobials upon wound healing remain controversial. Objective: To assess the clinical relevance of histological findings following antimicrobial applications on chronic leg ulcers. Method: The present study was performed in three parallel groups of 17 patients suffering from at least 2 similar chronic leg ulcers. Clinical planimetric assessments were performed before and after 3 and 6 weeks of treatment using hydrocolloid dressings. In addition, 1 ulcer in each patient received applications of povidone-iodine (PVP-I), silver sulfadiazine or chlorhexidine digluconate. Histological examinations were made at inclusion and after the 6-week therapy. Time to healing was also recorded. Results: At entry in the study, fibroblasts, macrophages, neutrophils and vessels were abundant in the ulcers. In addition, focal necrotizing vasculitis was related to the microbiological load. Compared to the control lesions, both the healing rate and time to healing of the leg ulcers showed a modest improvement at the sites receiving silver sulfadiazine (2–7%) or chlorhexidine digluconate (–1 to 5%). By contrast, PVP-I increased significantly the healing rate (4–18%, p < 0.01), and time to healing was reduced by 2–9 weeks (p < 0.01). The 3 antimicrobials decreased the bacterial density, and the vascular margination and migration of inflammatory cells, thus abating the vasculitic changes. PVP-I applications did not alter the microvessels and did not significantly reduce the density in dendrocytes and fibroblasts. By contrast, both silver sulfadiazine and chorhexidine digluconate appeared to alter the superficial microsvasculature including the dendrocyte population. Conclusion: Although topical antimicrobials may apparently achieve almost similar activity on the bacterial load inside chronic leg ulcers, the toxicity upon host cells was different among these agents. PVP-I appeared to be an efficient compound in these respects exhibiting a positive and relevant clinical effect.
Cystine Transport Activity of Heterozygous rBAT Mutants Expressed in Xenopus Oocytes
Authors: Ishihara Masanari , Ogura Takehiko , Akakura Koichiro , Egoshi Ken-ichi , Mikami Kazuo , Nakaya Haruaki , Ito Haruo
Published: April 2003

The rBAT gene encodes a transport protein for cystine and dibasic amino acids. It is a candidate gene for type I cystinuria, a genetic disorder inherited as an autosomal-recessive trait. Recently, several mutations in rBAT from Japanese patients with cystinuria have been reported from our laboratory. Some of these patients were heterozygous, which appears to be inconsistent with the previous concept that mutations in rBAT are recessive. To investigate the function of heterozygous mutants, we introduced these mutations into rBAT gene and analyzed the transport activity of cystine associated with the mutants in Xenopus oocytes. Co-injection of the mutant T1037C (L346P) and the polymorphism G1854A (M6181) into Xenopus oocytes produced a transport activity of 67.9% of the wild type. Oocytes co-injected with T2017C (C673R) and wild type had a transport activity of 70.3% of the wild type. These findings indicate that the heterozygous mutants show decreased transport activity compared to wild-type rBAT. Further, some mutants in rBAT may show decreased cystine transport activity even in heterozygous condition, which may contribute to stone-forming cystinuria.
The Role of Family and Partnership in Recovery from Alcohol Dependence: Comparison of Individuals Remitting with and without Formal Help
Authors: Rumpf Hans-Jürgen , Bischof Gallus , Hapke Ulfert , Meyer Christian , John Ulrich
Published: April 2003

The aim of this study was to analyse the role of family and partnership in remission from alcohol dependence in treated (n = 50) and untreated (n = 115) individuals. Standardised questionnaires to assess social support, social pressure, coping behaviour, and self-efficacy to stay remitted were used. In both media-solicited samples, social support increased from the pre- to the post-resolution period and was stated as an important resolution maintenance factor. Remitters with formal help experienced more partnership conflicts prior to remission and tended to experience more social pressure from their partner. Social support and social pressure from the family and partner were related to an increase in cognitive coping, as hypothesised, however, only in remitters without formal help, whereas an inverse relationship was found in formal help seekers. Implications for alcohol-related interventions are discussed.
Mal de Meleda: Genetic Haplotype Analysis and Clinicopathological Findings in Cases Originating from the Island of Mljet (Meleda), Croatia
Authors: Bakija-Konsuo A. , Basta-Juzbasic A. , Rudan I. , Situm M. , Nardelli-Kovacic Magdalena , Levanat Sonja , Fischer Judith , Hohl Daniel , Loncaric Davorin , Seiwert Sven , Campbell Harry
Published: April 2003

Background: Mal de Meleda (keratoderma palmoplantaris transgrediens) is an autosomal recessive disorder, first described on the island of Mljet (Meleda), Croatia. The candidate region for the gene responsible for this disorder was found on the chromosome 8qter, and the responsible mutations have recently been identified in 12 Algerian and 7 Croatian families. Objectives: To fully characterize all 12 living cases originating from the original setting of the disease, the island of Mljet, in the light of new findings and using modern diagnostic technology. Patients and Methods: Twelve patients and 37 family members were identified over the period 1998–1999, interviewed and examined. Results: The reconstruction of 8 genealogies suggests a common ancestry of all cases but one. The clinical presentation and pathologic findings of these cases are described in detail and are consistent with previous reports. Symptoms and signs were found to be milder in non-manual workers who had applied continuous symptomatic treatment. Blood samples were taken from 8 cases and 16 close relatives for genetic studies. These confirmed a shared haplotype in all cases, but in none of 17 unaffected control individuals, near the marker D8S1751 on chromosome 8. Conclusions: This review characterizes mal de Meleda in its original setting and shows that the sporadic cases found in the regions of medieval trade routes of the Republic of Dubrovnik (Middle East and Northern Africa) carry the same mutation as the patients from Mljet Island, Croatia.
Nephrotic Syndrome due to Immunologically Mediated Hypocomplementic Glomerulonephritis in a Patient of Waldenström’s Macroglobulinemia
Authors: Haraguchi Souichiro , Tomiyoshi Yoshiyuki , Aoki Shigehisa , Sakemi Takanobu
Published: April 2003

A 72-year-old man was diagnosed as having nephritic syndrome complicated by Waldenström’s macroglobulinemia (WM). A monoclonal IgM lamda protein and decreased serum complements were observed. The renal biopsy disclosed the capillary occluded by thrombi which was stained with IgG, IgA, IgM, C4, lamda light chain and slight kappa light chain in a granular pattern. Electron dense deposits were noted in the subendothelial spaces. An unusual case of WM who developed nephrotic syndrome due to immunologically mediated hypocomplementic glomerulonephritis is described.
Skin Tensile Properties in Patients Treated for Acromegaly
Authors: Braham Catherine , Betea Daniela , Piérard-Franchimont Claudine , Beckers Albert , Piérard Gérald E.
Published: April 2003

Background: Somatotropic effects are described in the skin. Indeed, acromegaly is in part clinically recognized by cutaneous coarsening. The actual changes in tensile properties associated with the cutaneous manifestations are largely unknown. Objectives: To study the relationships between the skin tensile properties and the severity of acromegaly as assessed by serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Patients and Method: Assessments were made in 13 patients with acromegaly treated by somatostatin agonists combined or not with surgery. A total of 39 age- and sex-matched healthy subjects served as controls. Skin tensile properties were measured on the forearm and nape of the neck using a computerized suction device. Results: Significant differences were yielded between the skin tensile properties in patients and normal subjects. The highest IGF-1 values in the patients’ medical records were positively correlated with both skin distensibility and biologic elasticity. The most recent IGF-1 serum levels were negatively correlated with the visco-elastic ratio. No correlations were yielded between any of the biomechanical parameters and GH levels, disease duration and treatment dosages, respectively. Conclusion: The skin in acromegaly appears to be functionally more redundant and elastic than normal skin. The biomechanical changes appear quite different from those observed in other diseases with collagen deposition such as diabetes mellitus and scleroderma.
Endothelial Dysfunction in Uraemia
Authors: Cross Jenny
Published: April 2003

Cardiovascular disease is a major cause of morbidity and mortality in chronic renal failure (CRF). The endothelium plays a central role in the control of many aspects of vascular function, and abnormalities may contribute to the generation of atherosclerosis. The endothelium produces a wide range of regulatory molecules which, in health, function in concert to provide a carefully balanced anti-atherogenic environment. Endothelial dysfunction has been repeatedly demonstrated in renal failure, is present in the absence of anatomically obvious disease and appears to be useful in the prediction of morbidity and mortality in other cardiovascular risk groups. One of the most intensively studied and important mediators of endothelial function is nitric oxide (NO), whose production is reduced in CRF. A number of possible mechanisms for reduced NO bioavailability have been investigated including substrate limitation, competitive inhibition of NO synthase by endogenous NO synthase inhibitors known to accumulate in renal failure, and premature quenching of NO by free radicals present in high concentrations in this group. A clearer understanding of the pathogenesis of endothelial dysfunction in CRF has potential clinical implications. It may provide avenues for therapeutic interventions before the onset of clinically obvious cardiovascular disease in this high-risk patient group.
Significance of Serotonin Transporter Gene 5-HTTLPR and Variable Number of Tandem Repeat Polymorphism in Attention Deficit Hyperactivity Disorder
Authors: Zoroğlu Süleyman Salih , Erdal Mehmet Emin , Alaşehirli Belgin , Erdal Nurten , Sivasli Ercan , Tutkun Hamdi , Savaş Haluk A. , Herken Hasan
Published: April 2003

The purpose of this study was to evaluate the relationship between attention deficit hyperactivity disorder (ADHD) and polymorphism of the two regions of the 5-HTT gene [variable number of tandem repeats (VNTR) and 5-HTTLRR] in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 71 patients with ADHD and 128 healthy controls. The 5-HTTLPR S/S genotype was significantly lower in the patients than in the controls (p = 0.018). Homozygous and heterozygous L variant predominated in the ADHD group. But the VNTR STin2.12/12 genotype was significantly less found in the patients than in the controls (p = 0.001). There was no significant difference between the frequency of the short (S), long, 10, and 12 alleles of both groups. The lack of an S/S variant of 5-HTTLPR polymorphism of the STin2.12/12 variant of VNTR polymorphism appears to be associated with an increased risk of ADHD.
Papulonodular Lichenoid and Pseudolymphomatous Reaction at the Injection Site of Hepatitis B Virus Vaccination
Authors: Stavrianeas N.G. , Katoulis A.C. , Kanelleas A. , Hatziolou E. , Georgala S.
Published: April 2003

Immunization with the hepatitis B virus (HBV) is effective and safe with an estimated incidence of adverse reactions, either local or systemic, of less than 0.1%. Cutaneous side effects are rare and include lichen planus (LP) and lichenoid reactions. We report the case of a 21-year-old female, in whom a persistent, papulonodular lesion developed at the site of the injection, 6 weeks after the second dose of the HBV. Histological examination revealed lichenoid and pseudolymphomatous features. In addition, sensitization to thiomersal, a vaccine constituent, was documented by patch testing. The association of LP with chronic liver disease is well established. Furthermore, less than 20 cases of lichen or lichenoid reactions, following HBV vaccination, have been reported. Although several arguments have been presented, it is still debated whether there is a causal association or the occurrence of LP following HBV vaccination is a simple coincidence. It has been speculated that a T-cell-mediated, graft-versus-host-like reaction, triggered by a sensitizing protein, is directed against keratinocytes expressing an epitope of hepatitis B surface antigen or a similar epitope. Our case may represent a localized lichenoid reaction to HBV vaccination, a local reactive hyperplasia or a persisting delayed hypersensitivity reaction to a vaccine constituent. This is the first case of a local lichenoid reaction at the injection site of the HBV vaccine, providing further documentation for a causal association linking the HBV vaccine with LP.
Heme Oxygenase-1 Localization in the Rat Nephron
Authors: Shepard Michelle , Dhulipala Prasad , Kabaria Sunit , Abraham Nader G. , Lianos Elias A.
Published: April 2003

Background/Aims: Renal tubules undergo oxidative injury in various nephropathies. It is unknown whether tubular cells possess mechanisms to attenuate this form of injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, may provide such a mechanism by reducing levels of free heme, a prooxidant molecule, and by limiting activity of heme-containing prooxidant enzymes. Determination of the distribution of HO-1 in the nephron may identify those segments where HO-1 can afford protection against oxidative injury. Methods: Rats were injected subcutaneously with two different inducers of HO-1: Stannous chloride and cobalt protoporphyrin. At completion of injections, frozen sections of kidneys were stained for HO-1 using a biotin-conjugated monoclonal anti-HO-1 antibody. To identify the origin of tubules staining positive for HO-1, Tetragonolobus purpureas (TP)-derived lectin and Arachnis hypogaea (AH)-derived lectin were applied to sequential sections of the kidney cortex. Results: In rats injected with either HO-1 inducer, HO-1 was immunolocalized in tubules but not in glomeruli. Staining of sequential sections with TP-derived lectin, which binds mainly to proximal tubular cells, was negative in the tubules that stained positive for HO-1. Staining of sequential sections with AH-derived lectin, which binds mainly to distal and collecting tubular cells, was positive in those tubules that were also positive for HO-1. Conclusion: In kidneys of rats injected with inducers of HO-1, distal and collecting tubular cells were identified as the main segments of the nephron that express HO-1. We suggest that the distal nephron, by expressing HO-1, may be less vulnerable to oxidative injury.