bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocrine and Non-Endocrine Actions of Ghrelin
Authors: Broglio Fabio , Gottero Cristina , Arvat Emanuela , Ghigo Ezio
Published: April 2003

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amounts were detected in bowel, pancreas, kidneys, the immune system, placenta, testes, pituitary, and hypothalamus. Ghrelin displays strong growth hormone (GH)-releasing action mediated by the activation of the so-called GH secretagogue (GHS) receptor (GHS-R) type 1a. GHS-R are concentrated in the hypothalamus-pituitary unit but are also distributed in other central and peripheral tissues. Apart from the potent GH-releasing action, ghrelin has other actions including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, influence on exocrine and endocrine pancreatic function as well as on glucose metabolism, cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system. The discovery of ghrelin opened many new perspectives of research in neuroendocrinology and metabolism, and even also in other fields of internal medicine as gastroenterology, immunology, oncology and cardiology. The possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact is obviously suggested and is receiving great attention.
IGF-I Transcript Levels in Whole-Liver Tissue, in Freshly Isolated Hepatocytes, and in Cultured Hepatocytes from Lean and Obese Zucker Rats
Authors: Tenoutasse S. , van Vliet G. , Ledru E. , Deal C.
Published: April 2003

Background: The mechanisms underlying the maintenance of normal to high rates of linear growth and plasma insulin-like growth factor I (IGF-I) levels in spite of a low growth hormone secretion in obese children remain unknown. Among the animal models of early-onset obesity, obese Zucker (fa/fa) rats (which are homozygous for an inactivating missense mutation in the leptin receptor) are particularly appropriate, because their linear growth shows this growth hormone independence. Methods: To study the regulation of IGF-I synthesis in this model, we have established primary cultures of hepatocytes derived from 12-week-old Zucker male obese and lean rats. The rat IGF-I gene contains six exons, and alternative splicing generates different mRNAs, one of which (called IGF-1B) has been shown to be decreased by fasting. We report steady state mRNA levels for IGF-I (all transcripts) and for IGF-IB in hepatocytes after 3 days in culture, in freshly isolated hepatocytes, and in whole-liver tissue. RT-PCRs using primers specific for IGF-I or IGF-IB were performed with two different internal competitors for quantification. Results: In primary cultures of hepatocytes, the IGF-IB mRNA was increased by >50-fold (p = 0.01) in cells derived from obese animals as compared with cells from lean animals. However, these transcript levels were not significantly different when measured in freshly isolated hepatocytes or in whole-liver tissue. Conclusions: Increased IGF-IB transcription could be an intrinsic characteristic of cultured hepatocytes harbouring leptin receptors that bear the fa mutation. However, the modulation of this characteristic by cell-cell interactions and by in vivo hormone and metabolic status remains to be studied.
Effects of Mitoxantrone on Multiple Sclerosis Patients’ Lymphocyte Subpopulations and Production of Immunoglobulin, TNF-alpha and IL-10
Authors: Gbadamosi Joystone , Buhmann Carsten , Tessmer Wiebke , Moench Andrea , Haag Friedrich , Heesen Christoph
Published: April 2003

We designed this longitudinal study to clarify the short- and long-term effects of mitoxantrone on the immune system in a subgroup of multiple sclerosis patients treated at our centre. After 14 days we found a highly significant sustained reduction of leucocytes, primarily affecting neutrophils and most lymphocyte subsets except for naive and activated T lymphocytes. The CD4/CD8 ratio and serum immmunoglobulin levels were not affected. Furthermore, whole blood-stimulated mononuclear cell IL-10 production showed a significant lower level 2 weeks treatment, whereas basal IL-10 as well as stimulated and basal TNF-α secretion showed no significant changes. Longitudinal data disclosed a persistent decrease of B lymphocytes, while secretion of immunoglobulins, IL-10, and TNF-α was not altered in the follow-up. In conclusion, we confirmed a selective short-term effect of mitoxantrone therapy on most lymphocyte subpopulations, but not on immunoglobulines or the pro- and anti-inflammatory cytokines TNF-α and IL-10, which do not serve as possible response markers.
Reformation of the Posterior Atlanto-Occipital Membrane following Posterior Fossa Decompression with Subsequent Constriction at the Craniocervical Junction
Authors: Tubbs R. Shane , Wellons III John C. , Oakes W. Jerry , Blount Jeffrey P.
Published: April 2003

The posterior atlanto-occipital membrane (PAO) contributes little to craniocervical stability and is generally underappreciated and incised with most suboccipital craniectomies. We report a case of a child who underwent posterior fossa decompression for Chiari I malformation with syringomyelia whose symptoms had not resolved months after surgery. A secondary exploratory operation revealed a healed constricting PAO which had been incised linearly at the initial operation. This patient’s symptoms improved soon after the second surgery. We propose that attention be given to this membrane, and if it is incised with underlying dura mater as in a standard posterior fossa decompression, it should be removed or cauterized separately and laterally to inhibit its reformation.
Cystic Schwannoma of the Anterior Tentorial Hiatus
Authors: Du Rose , Dhoot Jashdeep , McDermott Michael W. , Gupta Nalin
Published: April 2003

Intracranial schwannomas not arising from the facial, trigeminal, or vestibular nerves in the absence of neurofibromatosis are extremely rare. We report a case of a schwannoma arising in the region of the anterior tentorial hiatus and posterior cavernous sinus. A 17-year old girl presented with headaches and intermittent diplopia. An MRI of the brain revealed a heterogeneously enhancing mass adjacent to the free edge of the tentorium, superior to the cerebellopontine angle. An orbitozygomatic pterional craniotomy was done with complete resection of the tumor. Postoperatively, the patient remained neurologically intact. The clinical presentation and treatment of schwannomas arising in this location are discussed.
Management of CNS Mucormycosis in the Pediatric Patient
Authors: Hamilton John F. , Bartkowski Henry B. , Rock Jack P.
Published: April 2003

Rhinocerebral mucormycosis (RM) is a rare, rapidly progressive disorder caused by fungi from the Mucoraceae family. With extensive central nervous system involvement, this disease is uniformly fatal within weeks. Mucormycosis normally presents in poorly controlled diabetics, intravenous drug abusers and immunocompromised patients. Many have advocated radical surgical resection (i.e. exenteration of the cavernous sinus with carotid sacrifice and en bloc resection) with administration of amphotericin B. We present a case of mucormycosis involving the paranasal sinuses and cranial base in a pediatric patient who experienced long-term survival with a more limited resection. We also present a review of the relevant literature. A 14-year-old diabetic male presented with RM with involvement of the bilateral frontal lobes, right basal ganglia and temporal lobe. Additionally, there was involvement of the sphenoid sinus and right cavernous sinus with extension into the posterior fossa along the course of the trigeminal nerve and encasement with narrowing of the right carotid artery. The patient underwent sinus endoscopy with debridement of necrotic fungal tissue and bone. This was followed by craniotomy with evacuation of bifrontal, right temporal and basal ganglia abscesses in such a way that all abscess cavities communicated. An Ommaya reservoir was placed into the largest cavity. The patient continued to receive intrathecal and intravenous antibiotics as well as hyperbaric oxygen therapy. The patient was clinically and radiographically free of disease 1 year after diagnosis. While invasive RM is generally a fatal disease, this rare disorder can be treated successfully without radical resection, particularly if multimodality treatment options are implemented.
Ultrastructure of the Optic Nerve in Magnesium-Deficient Rats
Authors: Gong Huaqing , Takami Yumiko , Amemiya Tsugio
Published: April 2003

Purpose: The ultrastructure of the optic nerves in magnesium (Mg)-deficient rats was studied to elucidate the function of Mg. Methods: After delivery, mother Wistar Kyoto rats were fed a low-Mg diet containing 0.1 mg Mg/100 g diet with all other nutrients and distilled and deionized water. Infant rats were suckled by their mothers for 21 days and then fed the same Mg-deficient diet. Control mother rats were fed commercial rat pellets containing 24 mg Mg/100 g diet and all other nutrients. The optic nerves were examined by electron microscopy at 6 weeks of age. Results: In the Mg-deficient rats, serum Mg levels were significantly lower and calcium levels higher than in the control rats. Ultrastructural findings were: significantly fewer myelinated axons and significantly thinner myelin sheaths in the Mg-deficient rats than in the control and pair-fed controls, and more numerous unmyelinated axons. There were multifocal areas of destruction and necrosis in the optic nerve of Mg-deficient rats. Conclusions: This study suggests that the optic nerve needs Mg for the development and maintenance of its cell structure.
High Circulating Levels of Tumor Necrosis Factor-α in Centenarians Are Not Associated with Increased Production in T Lymphocytes
Authors: Sandmand Marie , Bruunsgaard Helle , Kemp Kåre , Andersen-Ranberg Karen , Schroll Marianne , Jeune Bernard
Published: April 2003

Background: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-α are strongly associated with morbidity and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-α levels are unknown. Objective: The aim of the present study was to investigate if high plasma levels of TNF-α are associated with increased production of TNF-α by T lymphocytes in elderly humans. Methods: TNF-α production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14 81-year-olds and 25 centenarians. Results: Plasma levels of TNF-α increased with increasing age. An increased percentage and number of T lymphocytes from the 81 year olds expressed TNF-α, whereas centenarians did not show this altered TNF-α secretion profile. Conclusion: T cells may contribute to the elevated levels of plasma TNF-α in healthy elderly subjects, whereas other mechanisms are responsible in very old individuals.
Associations of Biomarkers, Cognition and Self-Reports of Sensory Function with Self-Reported Driving Behaviour and Confidence
Authors: Anstey Kaarin J. , Smith Glen A.
Published: April 2003

Background: Older adults report self-regulating their driving habits but little is known about factors associated with driving habits and driving confidence. Objective: We aimed to evaluate cognitive performance, biomarkers and self-reported sensory function as correlates of self-reported driving behaviour and confidence. Methods: A volunteer sample of 153 drivers aged between 60 and 90 were assessed on biomarkers (vision, hearing, vibration sense, grip strength and FEV1), and cognitive performance. A subsample of 121 also completed a questionnaire on driving behaviour, driving confidence and self-reported sensory function. Structural equation modelling techniques were used to evaluate the relative importance of subjective and performance-based variables. Results: Driving behaviour and confidence were associated with cognitive performance, biomarkers, chronological age and one question on self-rated hearing difficulty. Structural equation modelling showed that biomarkers were most important in predicting self- reported driving behaviour. Conclusion: These results suggest that individuals self-monitor according to their physiological well-being and report their driving behaviour accordingly.
No Influence of Surgical Stress on Postoperative Leptin Gene Expression in Different Adipose Tissues and Soluble Leptin Receptor Plasma Levels
Authors: Schoof Ellen , Stuppy Anja , Harig Frank , Singer Helmut , Carbon Roman , Horbach Thomas , Kratzsch Jürgen , Rascher Wolfgang , Dötsch Jörg
Published: April 2003

As part of the postsurgical stress response, plasma leptin levels increase in-between 12 h postoperatively. Objective: To study the kinetics of leptin gene expression in different adipose tissues before and after severe surgical trauma in children and adults. Methods: In 22 adults and 23 children with cardiac and 19 adult patients with abdominal surgery, we measured plasma leptin concentrations preoperatively, 4 and 10–17 h postoperatively and quantified leptin mRNA expression by TaqMan real-time PCR in adipose tissue taken at the beginning and the end of surgery from subcutaneous, intrathoracic, omental and mesenteric fat. Plasma-soluble leptin receptor levels were measured in 23 children after cardiosurgery. Results: Plasma leptin levels doubled between 4 and 10–17 h postoperatively in adults (p < 0.001) as well as in children (p = 0.0002) with cardiac surgery. After abdominal surgery, 10–17 h postoperatively, plasma leptin concentrations increased significantly (p < 0.05). During the operation, leptin gene expression did not change in neither of the patient groups. Plasma-soluble leptin receptor levels decreased immediately after the onset of surgery and remained unchanged thereafter. Conclusions: Leptin gene expression is not up-regulated during surgery. The measured increase in plasma leptin after surgery does not result from elevated levels of soluble leptin receptor but may follow an up-regulation of leptin gene expression later after the operation due to postsurgical metabolic changes.
Hypocalcemic Cardiomyopathy due to Untreated Hypoparathyroidism
Authors: Altunbaş Hasan , Balcı Mustafa Kemal , Yazıcıoğlu Gökhan , Semiz Ender , Özbilim Gülay , Karayalçın Ümit
Published: April 2003

Hypocalcemic cardiomyopathy due to hypoparathyroidism is a very rare condition which is usually refractory to conventional treatment for cardiac failure but which responds favorably to restoration of normocalcemia. A 55-year-old man and a 46-year-old woman with a history of postoperative hypoparathyroidism presented with symptoms of cardiac failure and hypocalcemia. A presumptive diagnosis of dilated cardiomyopathy was considered by echocardiography and endomyocardial biopsies were consistent with cardiomyopathy. The coronary angiograms were normal and there was no apparent cause for dilated cardiomyopathy in these patients. The history of the patients and partial recovery of cardiac function after restoration of normocalcemia suggest that hypocalcemia was the cause of dilated cardiomyopathy.
Sex Differences in the Middle Ear of the Bullfrog (Rana catesbeiana)
Authors: Mason Matthew J. , Lin Chris C. , Narins Peter M.
Published: April 2003

Impedance transformation by the middle ear of terrestrial vertebrates is considered to be a function of the ossicular lever apparatus, which increases force and decreases velocity at the stapes footplate relative to the tympanic membrane, and the ratio of tympanic membrane area to stapes footplate area (the area ratio), which increases pressure at the stapes. A recent vibrometric study has found that the velocity ratio between tympanic membrane and stapes footplate is higher in male bullfrogs (Rana catesbeiana) than in females. Although the tympanic membrane area is known to be larger in male bullfrogs, the area ratio has apparently never been compared between the sexes. The hypothesis that a lower area ratio in males helps to compensate for the higher velocity ratio was investigated by comparing tympanic membrane, stapes footplate and operculum areas in frogs of both sexes. Contrary to expectation, the difference in stapes footplate area between males and females is very small, and area ratios are considerably higher in males. Area ratios increase with increasing body size in both sexes. Operculum area does not differ between the sexes. The apparent difference in impedance transformation between male and female frogs might be necessary due to different inner ear impedances, or might reflect serious inadequacies in the conventional models of middle ear function.
Differential Influence of Rearing Conditions and Methamphetamine on Serotonin Fibre Maturation in the Dentate Gyrus of Gerbils (Meriones unguiculatus)
Authors: Busche A. , Neddens J. , Dinter C. , Dawirs R.R. , Teuchert-Noodt G.
Published: April 2003

Environmental experience and drugs are two parameters that affect the maturation of neurotransmitter systems. The influence of impoverished rearing (IR) versus enriched rearing (ER) was compared in conjunction with postnatal methamphetamine (MA) treatment. The densities of immunostained 5-HT fibres were quantified in septal and temporal regions of the hippocampal dentate gyrus (DG) in young adult gerbils. In the IR group, 5-HT fibre densities were significantly increased in the molecular, granular and polymorphic layers of the DG in the temporal plane. After postnatal MA treatment, the 5-HT fibre density in the ER group reached a level equivalent to that of the IR group in nearly all respects. Under IR conditions, the pharmacological intervention significantly increased the maturation of fibre densities in septal layers only in the right hemisphere with no significant alterations in the left hemisphere and in temporal regions of either hemisphere. According to our previous studies on hippocampal neurogenesis, adaptations of 5-HT fibre densities partly proved to be positively correlated to cell proliferation rates for each of the specific conditions. Thus, the induced MA sensitivity, caused by pharmacological intervention at day 14, was manifested as direct interaction of 5-HT fibre maturation and cell proliferation in dependence of environmental factors. Both IR and MA together give us a better understanding of raphe-hippocampal plasticity and offer new perspectives for pharmacological studies on the 5-HT participation in mental disorders.
Implications of Removing a Normal Appendix
Authors: Bijnen C.L. , van den Broek W.T. , Bijnen A.B. , de Ruiter P. , Gouma D.J.
Published: April 2003

Background: The diagnosis of acute appendicitis remains difficult, and therefore 15–30% of the removed appendices appear to be normal. The aim of this study is to investigate the morbidity, mortality and costs of removing a normal appendix in patients with suspected appendicitis. Patients and Methods: A retrospective study was performed on patients who underwent a negative appendectomy for suspected appendicitis in the period 1991–1999 with a median follow-up of 4.4 years. Patients who underwent an elective appendectomy or appendectomy for other reasons were excluded. Results: In 285 patients (70% women, 30% men) a normal appendix was removed. In 192 (67%) patients a muscle-splitting incision was performed, in 6 (2%) a median laparotomy, and in 51 (18%) the normal appendix was removed by laparoscopy. In 36 patients (13%) a diagnostic laparoscopy was converted to a muscle-splitting incision. Complications occurred in 16 (6%) patients, in 5 (2%) a reoperation was needed. The mean hospital stay was 4.4 (SE 2.8) days, in case of complication 7.4 (SE 4.2) days. The mean extra hospital costs of a negative appendectomy were EUR 2,712. Conclusion: The removal of a normal appendix has considerable complications and costs. In an attempt to prevent these costs, extra diagnostic tools should be considered. Expensive diagnostic tools as diagnostic laparoscopy should be used selectively in order to not further exceed costs.
Hepatic Cryotherapy Involving the Vena cava
Authors: Eggstein S. , Neeff H. , Szarzynski M. , Jungraithmayr W. , Haberstroh J. , Kirste G. , Schmitt-Graeff A. , Farthmann E.H.
Published: April 2003

Liver tumors located near the retrohepatic vena cava are often considered nonresectable. For these patients cryoablation could be a therapeutic option. In this study the safety and efficacy of hepatic cryosurgery involving the retrohepatic vena cava were investigated. Cryolesions involving the vena cava were created in 26 pigs. Follow-up was 24 h and 14 days. The extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. The cyronecrosis extended into the wall of the vena cava in 81% of the animals. All animals had an uneventful recovery without any complications such as ruptures of the vessel, thrombosis or pulmonary embolism. Microscopically elastic and collagenous fibers of the cava wall remained intact. The continuity of the vessel wall was conserved. In conclusion, the safety and efficacy of cryosurgical treatment involving the retrohepatic vena cava were shown in a pig model.
Experimental Monkey Model Sensitized with Mite Antigen
Authors: Yasue Masaaki , Nakamura Shin , Yokota Toyokazu , Okudaira Hirokazu , Okumura Yasushi
Published: April 2003

Background: Monkeys are considered to have an immune system very similar to that of humans, as compared with mice, rats, and guinea pigs. Although primate allergic models to several pollen allergens have been developed, no model of house dust mite allergy has been reported. In this study, we attempted to induce type I allergy to mite allergens in rhesus monkeys. Methods: Six rhesus monkeys were immunized subcutaneously with crude mite extract adsorbed on aluminum hydroxide for 4 months. Then 5 monkeys positive for IgE production to mite extract were further immunized subcutaneously and conjunctivally with recombinant Der f 2 (rDer f 2). The status of sensitization to mite extract and rDer f 2 in monkeys was examined before and after the immunization. Plasma antigen-specific IgE and IgG levels, cutaneous reaction, and histamine release from peripheral blood leukocytes were measured. After conjunctival immunization, immediate conjunctivitis and leukocyte influx into conjunctiva after rDer f 2 challenge were examined. Results: After immunization with crude mite extract, 5 of 6 sensitized monkeys showed IgE response to the mite, and 4 out of 5 rDer f 2-sensitized monkeys exhibited IgE production to rDer f 2. Three monkeys sensitized with rDer f 2 showed immediate conjunctivitis and conjunctival eosinophilia after applying rDer f 2 to their eyes. Sensitized animals also showed IgG response to mite antigens. Conclusion: Four rhesus monkeys were positive for IgE production and allergic reactions to both mite extract and rDer f 2. These monkeys could represent a useful model for studying the development and regulation of house dust mite allergy.
Distribution of Small Intestinal Lesions in Anaphylaxis of Rats
Authors: Levine Seymour , Saltzman Arthur
Published: April 2003

Hemorrhage and congestion were not uniformly distributed along the small intestine during systemic anaphylaxis in rats. Duodenum had little hemorrhage and congestion and the terminal ileum had even less. Maximum involvement occurred in jejunum of 13% of rats, in ileum of 47%, and in both jejunum and ileum of 40%. Sequential scoring along the entire length of small intestine revealed different patterns of distribution with more than one peak of intensity in some of the rats. Within a lesioned area, banding was common except where hemorrhage and congestion were so severe as to obliterate all patterns. Banding represented a gradient of injury with respect to the vascular supply. The pale stripes (less severe hemorrhage) contained the penetrating vessels derived from the terminal mesenteric arcades. The dark stripes (more severe hemorrhage) did not contain such vessels. In addition, the mesenteric side of the intestine was less affected than the antimesenteric side. This constituted a second gradient that might also be related to the distance from the vascular supply. In both instances, proximity to larger blood vessels had a protective effect. These two gradients and the variable sites and patterns of distribution have not been described previously in intestinal anaphylaxis. Gradients and the variability of the distribution of lesions in intestinal anaphylaxis should be considered in experiments on pathogenesis and altered function.
Adherence to Secondary Stroke Prevention Strategies – Results from the German Stroke Data Bank
Authors: Hamann Gerhard F. , Weimar Christian , Glahn Joerg , Busse Otto , Diener Hans-Christoph
Published: April 2003

Only very limited data are available concerning patient adherence to antithrombotic medication intended to prevent a recurrent stroke. Reduced adherence and compliance could significantly influence the effects of any stroke prevention strategies. This study from a large stroke data bank provides representative data concerning the rate of stroke victims adhering to their recommended preventive medication. During a 2-year period beginning January 1, 1998, all patients with acute stroke or TIA in 23 neurological departments with an acute stroke unit were included in the German Stroke Data Bank. Data were collected prospectively, reviewed, validated and processed in a central data management unit. Only 12 centers with a follow-up rate of 80% or higher were included in this evaluation. 3,420 patients were followed up after 3 months, and 2,640 patients were followed up one year after their stroke. After one year, 96% of all patients reported still adhere to at least one medical stroke prevention strategy. Of the patients receiving aspirin at discharge, 92.6% reported to use that medication after 3 months and 84% after one year, while 81.6 and 61.6% were the respective figures for clopidogrel, and 85.2 and 77.4% for oral anticoagulation. Most patients who changed medication switched from aspirin to clopidogrel. Under the conditions of this observational study, adherence to stroke prevention strategies is excellent. The highest adherence rate is noticed for aspirin and oral anticoagulation. After one year, very few patients stopped taking stroke preventive medication.
Role of BK Potassium Channels Shaping Action Potentials and the Associated [Ca2+]i Oscillations in GH3 Rat Anterior Pituitary Cells
Authors: Miranda Pablo , de la Peña Pilar , Gómez-Varela David , Barros Francisco
Published: April 2003

Measurements of electrical activity and intracellular Ca2+ levels were performed in perforated-patch clamped GH3 cells to determine the contribution of large-conductance calcium-activated K+ (BK) channels to action potential repolarization and size of the associated Ca2+ oscillations. By examining the dependence of action potential (AP) duration on extracellular Ca2+ levels in the presence and the absence of the specific BK channel blocker paxilline, it is observed that plateau-like action potentials are associated to low densities of paxilline-sensitive currents. Extracellular Ca2+ increases or paxilline additions are not able to largely modify action potential duration in cells showing a reduced expression of BK currents. Furthermore, specific blockade of these currents with paxilline systematically elongates AP duration, but only under conditions in which short APs and/or prominent BK currents recorded under voltage-clamp mode are present in the same cells. Our data indicate that in GH3 cells, BK channels act primarily ending the action potential and suggest that by contributing to fine-tuning cellular electrical properties and hence intracellular Ca2+ variations, BK channels may play an important role on time- and cell-dependent modulation of physiological outputs in adenohypophyseal cells.
Critical Role of IL-5 in Antigen-Induced Pulmonary Eosinophilia, but Not in Lymphocyte Activation
Authors: Matsumoto Nobuhiro , Katoh Shigeki , Mukae Hiroshi , Matsuo Takeshi , Takatsu Kiyoshi , Matsukura Shigeru
Published: April 2003

Infiltration of antigen-specific CD4+ T cells and production of interleukin (IL)-5 in inflammatory regions play a central role in antigen-induced pulmonary eosinophilia. Genetically IL-5-deficient mice lack antigen-induced airway eosinophilia, but little is known about the role of IL-5 in accumulation and activation of CD4+ T cells in the lung and in airway hyperresponsiveness (AHR). Ascaris suum extract (Asc) has been used to induce airway eosinophilia and analyze airway inflammation in IL-5 receptor α-chain-deficient (IL-5RKO) mice. We examined the role of IL-5 in CD4+ T cell activation, cytokine production, and AHR upon Asc sensitization. Pulmonary CD4+ T cells in Asc-immunized mice were activated and produced IL-5 upon local exposure to Asc in both wild-type (WT) and IL-5RKO mice. IL-2, IL-4, IL-5, IL-10 and eotaxin were detected in bronchoalveolar lavage fluid of both WT and IL-5RKO mice following exposure to Asc. Airway eosinophilia and AHR were seen only in WT mice, but not in IL-5RKO mice. We conclude that IL-5 appears to be required for the accumulation of eosinophils and AHR in the inflammatory lung. However, IL-5 does not play a critical role in the accumulation of activated CD4+ T cells in the inflammatory lung.
Acute Stress Results in Skin Corticotropin-Releasing Hormone Secretion, Mast Cell Activation and Vascular Permeability, an Effect Mimicked by Intradermal Corticotropin-Releasing Hormone and Inhibited by Histamine-1 Receptor Antagonists
Authors: Lytinas Michael , Kempuraj Duraisamy , Huang Man , Boucher William , Esposito Pamela , Theoharides Theoharis C.
Published: April 2003

Background: Mast cells play an important role in allergic inflammation by releasing vasoactive molecules, proteases and cytokines. Corticotropin-releasing hormone (CRH) and its structural analogue urocortin (Ucn) were shown to trigger skin mast cell activation and vascular permeability. We investigated the effect of acute stress on rat skin vascular permeability and CRH secretion, as well as the effect of intradermal CRH, and that of two histamine-1 receptor antagonists, azelastine and olopatadine, on vascular permeability. Methods: Rats were stressed by restraint and vascular permeability was assessed by extravasation of 99Tc-gluceptate, while mast cell activation was determined by skin rat mast cell protease-1 (RMCP-1) content. Skin CRH content was evaluated by ELISA. The effect of intradermal injection of CRH and Ucn, as well as that of two histamine-1 receptor antagonists, azelastine and olopatadine, was assessed by Evan’s blue extravasation. Purified rat peritoneal mast cells (RPMCs) were also pretreated with azelastine (24 µM) or olopatadine (133 µM) for 5 min before challenge with compound 48/80 (0.5 µg/ml) for 30 min. Histamine secretion was measured fluorometrically. Intracellular Ca2+ ions were evaluated in RPMCs loaded with calcium crimson and stimulated with compound 48/80. Results: Acute stress increased skin vascular permeability and CRH content, while it decreased RMCP-1. Intradermal injection of CRH or Ucn induced substantial Evan’s blue extravasation that was inhibited by pretreatment with azelastine (24 µM) and olopatadine (133 µM). Both antihistamines also inhibited histamine release and intracellular increase of Ca2+ ions from RPMCs stimulated by compound 48/80. Conclusions: These results indicate that acute stress increases skin CRH that can trigger mast cell-dependent vascular permeability, effects inhibited by certain histamine-1 receptor antagonists, possibly acting to reduce intracellular Ca2+ ion levels.
Characterization of Exposure to Low Levels of Viable Penicillium chrysogenum Conidia and Allergic Sensitization Induced by a Protease Allergen Extract from Viable P. chrysogenum Conidia in Mice
Authors: Schwab Christopher J. , Cooley J. Danny , Brasel Trevor , Jumper Cynthia A. , Graham Suzanne C. , Straus David C.
Published: April 2003

Background: Previous evidence by our laboratory has shown that mice inoculated with viable Penicillium chrysogenum conidia or spores at levels comparable to those found in contaminated buildings induced spore antigen-specific allergic responses. We proposed that mice exposed to low levels of viable P. chrysogenum conidia would not develop allergic symptoms. We also hypothesized that the symptoms induced by high numbers of conidia were the result of sensitization to allergens released by the conidia. Methods: C57BL/6 and BALB/c mice were exposed to 1 × 102 viable P. chrysogenum conidia by intranasal instillation weekly for a period of 11 weeks. C57BL/6 mice were also sensitized to a viable P. chrysogenum conidia protease extract by intraperitoneal injections for a period of 6 weeks followed by intranasal challenge with protease extract, viable, or nonviable P. chrysogenum conidia for 2 weeks. Results: C57BL/6 mice inoculated with low numbers of conidia developed no significant lung inflammation or increased serum immunoglobulins. Mice sensitized to the protease extract and challenged with both protease extract and viable conidia produced significant increases in serum IgE and IgG1. Mice sensitized to and challenged with the protease extract developed significant eosinophilia and mucus hyperproduction as determined by bronchoalveolar lavage and histopathological examination of lung tissue. Conclusions: Mice did not develop allergic symptoms in response to challenge with low levels of P. chrysogenum conidia. Protease allergens from viable conidia induced specific allergic responses in mice, indicating the importance of P. chrysogenum conidia in allergic sensitization to the organism.
Persistent, Unwanted Erections in an 8-Year-Old Boy
Authors: Montgomery John H. , Waller David A. , Robinson Roger
Published: April 2003

Although unusual somatic preoccupations can be seen in somatoform disorders and obsessive-compulsive disorder (OCD), unwanted penile erections have been described only in two cases of OCD, both adults. In the present case an 8-year-old boy developed unwanted erections, other obsessive-compulsive symptoms, as well as symptoms of posttraumatic stress disorder, such that he met criteria for both disorders. Treatment consisted of sertraline combined with individual play therapy and family therapy, following which the patient reported modest improvement in symptoms of both disorders.
Subjective Experience of Language Impairment and Psychopathology in Schizophrenia
Authors: Maggini Carlo , Raballo Andrea , Pelizza Lorenzo , Paini Matteo , Croci Roberto
Published: April 2003

The principal concern of this paper lies in the exploration of the possible role of the subjective experience of language impairment in shaping schizophrenic symptomatology. A previous model embracing the basic symptom theory and the vulnerability paradigm hypothesized that (self-perceived) impairment of receptive and expressive language and alexithymia may play a relevant role in facilitating the development of a nonparanoid prototype of schizophrenia. The experimental protocol which led to this model [emphasizing the comprehensive notion of ‘language capacity’ as pathoplastic modulator of overt schizophrenic syndromes (i.e. pathoplastic model)] was replicated on a wider schizophrenic sample, assessing contextually with diagnostic symptoms, depressive symptoms, alexithymia, subjective experience of negative symptoms and hedonic capacity. Since schizophrenics with self-experienced language capacity impairment did not differ from other schizophrenics, as regards positive, negative and disorganized symptoms, but just in negative symptom-related distress, an alternative interpretation of the possible role of the subjective experience of language impairment in schizophrenic psychopathology is proposed (i.e. idioplastic hypothesis).
Report of a Case with Polymicrobial Endocarditis Related to Multiresistant Strains
Authors: Kocazeybek Bekir , Ozder Ayşe , Kucukoglu Serdar , Kucukates Emine , Yuksel Husniye , Olga Rustem
Published: April 2003

We present a patient with polymicrobial endocarditis who had been operated on previously for a mycotic aneurysm and was seen at the cardiology clinic because of palpitations related to effort. A transesophageal echocardiogram revealed a 15-mm vegetation on his aortic valve. Staphylococcus epidermidis and Corynebacterium striatum were isolated from the blood cultures. Both strains were multiresistant (susceptible to 3 antibiotics at most) against chemotherapy in vitro. Microbiological eradication was not achieved from blood cultures even after applying antimicrobial therapy with effective antibiotics as determined with an antibiotic susceptibility test. For this reason, the patient underwent valve replacement. He was discharged from hospital in fairly good health.
Keratolytic Activity of Microemulsions
Authors: Gloor M. , Haus G. , Keipert S.
Published: April 2003

Objective: To compare the keratolytic activities of a drug-free hydrophilic microemulsion (ME) and a drug-free lipophilic ME with water, and with regard to the hydrophilic ME also with a 5% salicylic acid gel on the sole of the foot. Methods: Twenty healthy volunteers had their plantar forefoot, midfoot, and rearfoot stratum corneum blackened with silver nitrate and a photographic developer, and a chromameter was used to determine the extent of removal of this black dye by a* value and L value measurement at 24 and 48 h. Results: Both drug-free MEs produced significantly greater increases in a* value and L value than water, and the hydrophilic ME was also more effective than 5% salicylic acid gel. Conclusion: The irritating effect of MEs is rather negligible on the sole of the foot because of the thick plantar stratum corneum. Both MEs therefore appear suitable for the elimination or prevention of plantar desquamative and hyperkeratotic skin changes.
Transcriptional Activity of Potent Glucocorticoids: Relevance of Glucocorticoid Receptor Isoforms and Drug Metabolites
Authors: Spika I. , Hammer S. , Kleuser B. , Korting H.C. , Schäfer-Korting M.
Published: April 2003

As compared to standard glucocorticoids (GC), prednicarbate (PC) is favorable in the treatment of eczema due to its high benefit/risk ratio. The remarkable anti-inflammatory effects of PC are in strong contrast to its reported low glucocorticoid receptor (GR) binding affinity. In transfected COS-7 cells we related the transcriptional potencies of PC, its metabolites and conventional GC to their receptor binding properties. Moreover, the expression pattern of the human GR isoform hGRα and its mutual dominant negative inhibitor hGRβ in skin cells have been investigated as well as the influence of hGRβ on receptor binding and transactivation. hGRα mRNA and protein was largely overexpressed in skin cells. hGRβ showed no influence on hGRα binding and transactivation. Concentration response curves indicated the greater transactivation potency of betamethasone 17-valerate followed by dexamethasone and prednisolone 17-ethylcarbonate. Native PC appeared almost as potent as dexamethasone. With both a strong correlation was observed between transactivation and GR binding.
Cystatin C as an Endogenous Marker of Glomerular Filtration Rate in Renal Transplant Patients
Authors: Pöge U. , Stoschus B. , Stoffel-Wagner B. , Gerhardt T. , Klehr H.U. , Sauerbruch T. , Woitas R.P.
Published: April 2003

Background: Serum creatinine is the most common endogenous marker used to estimate the glomerular filtration rate (GFR). However, creatinine depends considerably on muscle mass, and its tubular secretion increases, especially in chronic renal failure. Cystatin C is a 13-kD protease inhibitor which is produced by all nucleated cells and is independent of muscle mass and sex. Cystatin C is eliminated by glomerular filtration and metabolized by proximal tubular cells. Its measurement has been proposed as an alternative and more sensitive marker of GFR than creatinine in patients with slight to moderately decreased GFR. Methods: We investigated serum cystatin C levels in comparison with creatinine as a single measurement for estimation of GFR in 173 patients after renal transplantation. GFR was calculated as creatinine clearance according to standard equations. Results: Serum creatinine correlated well with cystatin C (r = 0.84; p < 0.0001). No significant differences were obtained for the comparison of the linear correlation of 1/creatinine with creatinine clearance (r = 0.77; p < 0.0001) and for the linear correlation of 1/cystatin C with creatinine clearance (r = 0.73; p < 0.0001). However, we found a significant advantage of cystatin C in detecting a clinical relevant reduction of kidney function (GFR <70 ml/min; p = 0.0047, McNemar test). Conclusion: Cystatin C is an alternative marker for the assessment of GFR in renal allograft recipients that may be superior to creatinine.
Influence of the Alpha-Adducin and ACE Gene Polymorphism on the Progression of Autosomal-Dominant Polycystic Kidney Disease
Authors: Merta M. , Reiterová J. , Stekrová J. , Rysava R. , Rihová Z. , Tesař V. , Viklický O. , Kmentova D.
Published: April 2003

Background: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability can not be fully explained by the genetic heterogenity of the disease. We examined the influence of the ACE I/D polymorphism, adducin Trp460Gly polymorphism and the association of both polymorphisms on the progression of ADPKD towards end-stage renal failure (ESRF). Methods: 320 ADPKD patients (pts) were analyzed, 220 pts (113 males, 107 females) with ESRF before 63 years of age, with a subgroup (rapid progressors) of 20 pts (12 males, 8 females) with ESRF before 40 years of age, 52 pts (23 males, 29 females) with ESRF later than 63 years of age (slow progressors), 48 ADPKD pts (18 males, 30 females) with mean age ±50 years with serum creatinine <110 µmol/l (slow progressors) and 200 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for the ACE I/D polymorphism and the Trp460Gly of α-adducin gene polymorphism. Results: The α-adducin genotypes showed no differences among the groups of slow progressors (74% Gly/Gly, 22.9% Gly/Trp and 3.1% Trp/Trp), pts with ESRF before 63 years of age (67.7% Gly/Gly, 30.5% Gly/Trp and 1.8% Trp/Trp) and rapid progressors (75% Gly/Gly, 25% Gly/Trp). The ACE genotypes did not differ among the groups of slow progressors (27.1% I/I, 44.8% I/D and 28.1% D/D), pts with ESRF before 63 years of age (23.6% I/I, 51.4% I/D and 25% D/D) and rapid progressors (20% I/I, 55% I/D and 25% D/D). The distribution did not differ from the control group. The ages of ESRF according to different genotypes did not significantly differ. We observed a significant tendency to better prognosis in Trp allele carriers for I/I genotype in comparison with Gly/Gly homozygous subjects. Conclusion: The ACE and α-adducin polymorphisms do not play a significant role in the progression of ADPKD to ESRF.
Chromosome assignment of eight SOX family genes in chicken
Authors: Kuroiwa A. , Uchikawa M. , Kamachi Y. , Kondoh H. , Nishida-Umehara C. , Masabanda J. , Griffin D.K. , Matsuda Y.
Published: April 2003

Chromosome locations of the eight SOX family genes, SOX1, SOX2, SOX3, SOX5, SOX9, SOX10, SOX14 and SOX21, were determined in the chicken by fluorescence in situ hybridization. The SOX1 and SOX21 genes were localized to chicken chromosome 1q3.1→q3.2, SOX5 to chromosome 1p1.6→p1.4, SOX10 to chromosome 1p1.6, and SOX3 to chromosome 4p1.2→p1.1. The SOX2 and SOX14 genes were shown to be linked to chromosome 9 using two-colored FISH and chromosome painting, and the SOX9 gene was assigned to a pair of microchromosomes. These results suggest that these SOX genes form at least three clusters on chicken chromosomes. The seven SOX genes, SOX1, SOX2, SOX3, SOX5, SOX10, SOX14 and SOX21 were localized to chromosome segments with homologies to human chromosomes, indicating that the chromosome locations of SOX family genes are highly conserved between chicken and human.
Interspecific hybridization induced amplification of Mdm2 on double minutes in a Mus hybrid
Authors: Brown J.D. , Strbuncelj M. , Giardina C. , O’Neill R.J.
Published: April 2003

We report a case of interspecific hybridization induced amplification of Chromosome 10 on double minutes (dm) in the karyotype of a hybrid Mus embryo. Stable, non-mosaic dm were previously found in tissues of a 16.5-day Mus musculus × Mus caroli hybrid (Graves, 1984). Dm in tissues of the hybrid was of interest to us because of previous reports of genomic instability in interspecific hybrids (O’Neill et al., 1998) and thus we decided to characterize the dm in the hybrid karyotypes. Whole chromosome painting of the hybrid cell lines showed amplification of Chromosome 10 sequences. Southern analysis with a probe for the candidate gene Mdm2 showed amplification of the paternal allele of this oncogene. Overexpression of Mdm2 was confirmed by a western analysis that also showed an associated inactivation of the tumor suppressor, Trp53. Evidence indicates that the event leading to the instability observed was an early adaptive response to stress on the genome, i.e. interspecific hybridization.
Hemihypertrophy and the Chiari I Malformation
Authors: Tubbs R. Shane , Smyth Matthew D. , Wellons III John C. , Oakes W. Jerry
Published: April 2003

We report two children with hemihypertrophy and Chiari I malformation (CIM) and review the extant medical literature regarding CIM and overgrowth disorders. We propose that these two entities do not represent a spurious association but rather share a common dysembryology of mesoderm.
Life Expectancy of Ventriculosubgaleal Shunt Revisions
Authors: Tubbs R. Shane , Smyth Matthew D. , Wellons III John C. , Blount Jeffrey P. , Grabb Paul A. , Oakes W. Jerry
Published: April 2003

The subgaleal shunt has been and is currently used for the temporary bypass of the normal cerebrospinal fluid (CSF) pathways. We retrospectively reviewed all subgaleal shunts placed at the Children’s Hospital, Birmingham, Ala., USA, from 1993 to the present and examined the life expectancy of revisions of this temporary method of CSF diversion. The average length of survival of primary, secondary and tertiary subgaleal shunts in this population was 37.4, 32.4 and 19.6 days, respectively. This current review demonstrates that the majority of patients in whom a subgaleal shunt is utilized may continue to obtain therapeutic diversion of their CSF for greater than 2.5 months with intermittent subgaleal shunt revisions. In the majority of cases, this length of time is sufficient to manage and resolve issues that would make ventriculoperitoneal shunting undesirable.
Spontaneous Resolution of Calvarial Eosinophilic Granuloma in Children
Authors: Oliveira Marcelo , Steinbok Paul , Wu John , Heran Navraj , Cochrane Douglas
Published: April 2003

Objective: The recommended treatment for solitary calvarial eosinophilic granuloma (EG) is surgical resection by curettage, craniectomy or craniotomy. The purpose of this study was to describe the spontaneous resolution of calvarial EG and discuss ‘observation only’ as an option in the management of this condition. Methods: A retrospective review was performed of children with calvarial EG seen at a tertiary care children’s hospital. Of a total of 17 such patients, four were managed without any intervention and formed the basis of this report. Results: In all four patients treated by ‘observation only’, there was a tender calvarial mass which enlarged rapidly over a few days and then resolved slowly over many weeks. The diagnosis of EG was based on the findings of plain radiographs and/or computed tomography. All masses had resolved by 8 weeks, and the underlying cranial defect filled in spontaneously in all cases. There was no recurrence at follow-up, which ranged from 2 months to 7 years. Conclusions: ‘Observation only’ should be considered as a viable option in the management of children with solitary calvarial masses that have the radiographic features of EG. Consideration should be given to delaying surgical intervention to allow time to see if spontaneous resolution occurs.