bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitizing Capacity and Residual Allergenicity of Hydrolyzed Cow’s Milk Formulae: Results from a Murine Model
Authors: Niggemann Bodo , Nies Hartmut , Renz Harald , Herz Udo , Wahn Ulrich
Published: April 2003

Background: Cow’s milk allergy is the most common cause of clinically relevant adverse reactions to food in infants and children. Partially and extensively hydrolyzed formulae are used for the therapy and prevention of cow’s milk allergy. However, the immunogenic potency of hydrolyzed cow’s milk formulae to induce and/or enhance the allergic phenotype in vivo is still under debate. The aim of this study was to assess the sensitizing capacity and residual allergenicity of various partially and extensively hydrolyzed cow’s milk formulae in a murine model of cow’s milk allergy. Methods: BALB/c mice were immunized with either a cow’s milk formula or various partially and extensively hydrolyzed formulae. Immediate cutaneous hypersensitivity reactions and allergen-specific antibody production were assessed. Results: Although immunization with cow’s milk resulted in 12/13 cases in a positive skin test response to intradermal injection of cow’s milk formulae, only 1 mouse showed a positive skin test to one of the partially hydrolyzed formulae, and none showed positive reactions to other partially hydrolyzed formulae, any of the extensively hydrolyzed formulae, phosphate-buffered saline or the amino acid formula. However, 6 of 8 mice showed positive skin tests when immunized with partially hydrolyzed formulae and with one of the extensively hydrolyzed formulae. Conclusions: The residual allergenic potential is markedly reduced in many hydrolyzed formulae, but most of the formulae investigated could induce an allergic immune response in BALB/c mice. Our murine model seems to be suitable to investigate the sensitizing capacity of hydrolyzed formulae and to differentiate even between extensively hydrolyzed formulae.
Effect of Emedastine Difumarate on CC Chemokine-Elicited Eosinophil Migration
Authors: Saito Hiroshi , Yamamoto Naomi , Tomita Syogo , Taniguchi Masami , Hasegawa Maki , Akiyama Kazuo , Kawaguchi Hiroshi , Takahashi Kazuo
Published: April 2003

Emedastine difumarate (emedastine) is an antiallergic drug found among the derivatives which has a series of benzimidazole frames. It has been reported that emedastine can significantly inhibit the migration of eosinophils elicited by classical chemoattractants, including LTB4 or PAF. However, the effect of emedastine on the selective migration of eosinophils that have been stimulated with CC chemokines has not been examined. Emedastine at concentrations of 10 nM or higher strongly inhibited the eosinophil migration elicited by CC chemokines, including eotaxin, RANTES and MCP-3. Preincubation of the eosinophils with emedastine did not alter the expression of the CCR3 receptor, although a decrease in the concentration of intracellular calcium ions was observed after stimulation with 100 ng/ml of eotaxin. Herbimycin A, genistein, staurosporin and emedastine were all able to inhibit the eotaxin-elicited migration. Tyrosine kinase activity in the cytosol supernatant of eosinophils obtained after stimulation with eotaxin significantly decreased when the eosinophils were preincubated with emedastine. In addition, protein kinase A and protein kinase C activities in eotaxin-stimulated EoL-1 cell supernatants decreased significantly with emedastine pretreatment. These findings suggest that emedastine inhibits CC chemokine-elicited eosinophil migration by decreasing the activities of tyrosine kinase or protein kinases but does not alter CCR3 expression.
Development of the Capacity of Peripheral Blood Mononuclear Cells to Produce IL-4, IL-5 and IFN-γ upon Stimulation with House Dust Mite in Children with Atopic Dermatitis
Authors: Kimura Mitsuaki , Yamaide Akiko , Tsuruta Satoru , Okafuji Ikuo , Yoshida Takami
Published: April 2003

Background: Imbalances of IL-4 and IFN-γ production are widely known to increase IgE synthesis in allergic individuals, and IL-5 is known to play a critical role in the pathogenesis of various allergic diseases. However, little is known about how Th cells specific to house dust mite (HDM) develop the capacity to produce these cytokines in children with atopic dermatitis (AD). Objective: This study aims to clarify when HDM-specific Th cells develop the capacity to produce IL-4, IL-5 and IFN-γ in children with AD. Methods: The production of IL-4, IL-5 and IFN-γ by peripheral blood mononuclear cells (PBMCs) upon stimulation with HDM was measured in 91 children with AD and 37 control subjects. The changes in the cytokine production with age were analyzed transectionally and longitudinally. Results: IL-4 production by HDM-stimulated PBMCs in children with AD was already increased before age 1. Thereafter, it continuously rose until reaching a near-maximum level at age 2. Growth-related changes in the production of IL-5 resembled those in the production of IL-4 and peaked at age 1. The production of these cytokines was very low in control subjects up to age 2 and then gradually increased, albeit never above the levels measured in AD children. The production of IFN-γ in children with AD reached a near-maximum level during the first year of life and diminished after age 3. Although IFN-γ production in controls was lower than that in AD children during infancy, it continuously rose even after age 3 and surpassed the levels measured in AD children. The level of serum HDM-specific IgE antibody began to increase after age 1 following the rise of IL-4 production. Essentially the same relationship among IL-4, IFN-γ and IgE synthesis was seen in a longitudinal study of 6 AD infants, in whom HDM-specific IgE was initially negative but later turned positive. Conclusions: These findings suggest that the capacity of HDM-specific Th cells to produce IL-4, IL-5 and IFN-γ develops and effectively matures during the first 3 years of life in children with AD.
Apoptosis in Maternal Peripheral Blood during Pregnancy
Authors: Kolialexi A. , Tsangaris G.Th. , Antsaklis A. , Tzortzatou F. , Amentas C. , Koratzis A. , Mavrou A.
Published: April 2003

Objective: To investigate the mononuclear cell apoptosis rate during pregnancy. Materials and Methods: Apoptosis was quantitated by EtBr staining in whole peripheral blood samples of 135 women in different gestational weeks and 85 nonpregnant women used as controls. Apoptosis was also qualitated by TUNEL assay. Results: The apoptosis rate increased during pregnancy according to gestational age. In chromosomally abnormal fetuses apoptosis was 2.5-fold higher than that found in pregnancies with normal embryos matched for gestational age. FISH in TUNEL-positive cells using X, Y and 21 chromosome probes verified the fetal origin of part of the apoptotic population. Conclusion: Apoptosis is stimulated in maternal peripheral blood during pregnancy, possibly accounting partly for the presence of free fetal DNA in maternal serum. The increased apoptosis rate in pregnancies with chromosomally abnormal fetuses may have additional clinical importance.
Endoscopic Ligation of Umbilical Cord at 19 Week’s Gestation in Monoamniotic Monochorionic Twins Discordant for Hypoplastic Left Heart Syndrome
Authors: Young Bruce K. , Roqué Hank , Abdelhak Yaakov , Timor-Tristch Ilan , Rebarber Andrei , Rosen Robert
Published: April 2003

We report the first attempt of reduction of monoamniotic twins, discordant for hypoplastic left heart syndrome, using a new fetoscopic technique. Employing sonographic guidance and endoscopic visualization, cord ligation was accomplished, but significant cord entanglement, not previously appreciated, resulted in the ligation of the umbilical cord of the normal fetus. Cord entanglement may frustrate endoscopic techniques in monoamniotic twins.
Congenital Cystic Adenomatoid Malformation of the Lung Coexisting with Recombinant Chromosome 18
Authors: Roberts D. , Sweeney E. , Walkinshaw S.
Published: April 2003

Objective: Diagnosis of congenital cystic adenomatoid malformation of the lung (CCAM) in association with recombinant chromosome 18. Method: Ultrasound diagnosis of a CCAM and hydrops was made. The mother was known to have a pericentric inversion of chromosome 18 and had a previous pregnancy with a recombinant chromosome 18 (partial deletion of 18p and partial duplication of 18q). Cordocentesis for karyotype was therefore performed. Result: Fetal karyotype revealed a recombinant chromosome 18, this time with partial deletion of 18q and partial duplication of 18p. Postmortem confirmed a type III CCAM and a septum primum atrial defect. Conclusions: Although deletion/duplication of chromosome 18 is commonly associated with a wide variety of anomalies, the association with CCAM is an unusual one. Fetal and parental karyotyping should be considered in cases of CCAM, because fetal therapy is increasingly being considered in these pregnancies. Current management of parents with pericentric inversions must rely on invasive diagnostic testing in the second trimester because predicting the likelihood of an unbalanced karyotype and phenotype in a fetus is difficult.
Outcome of Fetal Cystic Hygroma and Experience of Intrauterine Treatment
Authors: Ogita Keiko , Suita Sachiyo , Taguchi Tomoaki , Yamanouchi Takeshi , Masumoto Kouji , Tsukimori Kiyomi , Nakano Hitoo
Published: April 2003

Objective: To review our cases of fetal cystic hygroma and to examine the prognostic factors with the goal of establishing criteria for the intrauterine treatment for cystic hygroma. Patients and Methods: Thirty-one cases of fetal cystic hygroma were managed by us from January 1988 to December 1997, and 21 cases were available for analysis. Three prognostic factors, namely chromosomal abnormality, structural anomaly and hydrops fetalis, were evaluated. We treated 2 cases of cystic hygroma associated with hydrops fetalis in utero using OK-432 injection under ultrasound guidance. Results: The fetuses without any of the prognostic factors listed above showed a good prognosis throughout the fetal and neonatal periods. However, in this group, 2 infants with large tumors died of hemorrhage from the tumor at 6 months and 3 years of age, respectively. Cases with hydrops fetalis without chromosomal abnormalities or structural anomalies (5 cases) resulted in either intrauterine fetal death (IUFD, 2 cases) or early perinatal neonatal death (early PND, 3 cases). The cause of early PND was circulatory failure. Most of the hydrops cases with either a chromosomal abnormality or structural anomaly resulted in IUFD before 22 weeks of gestation. The size of the cyst decreased in 1 of 2 cases treated in utero. Conclusions: The fetal cases of cystic hygroma showing hydrops fetalis without chromosomal abnormalities or structural anomalies are considered to be possible candidates for intrauterine therapy. Those with very large cystic hygroma without any of the three prognostic factors are also thought to be candidates for fetal treatment. Based on our clinical experience, sclerotherapy using OK-432 is considered to be a treatment option in selected cases with fetal cystic hygroma.
Extreme Elevation of Maternal Serum Alpha-Fetoprotein Associated with Mosaic Trisomy 8 in a Liveborn
Authors: Miller R.I. , Stephan M.J. , Hume R.F. , Walker W.O. , Kelly P. , Calhoun B.C. , Hoeldtke N.J. , Hayden J.E. , Martin L.S.
Published: April 2003

Constitutional mosaic trisomy 8 has been associated with syndromic dysmorphology, corneal opacities, leukemias, and trophoblastic disease. However, abnormal maternal serum alpha-fetoprotein (MSAFP) has not been reported in association with mosaic trisomy 8. Our case first presented for evaluation of an extremely elevated MSAFP with mild elevation of MShCG in an otherwise normal pregnancy: MSAFP 13.89 MoM, MShCG 3.57 MoM, and MSuE3 1.04 MoM. Fetal dysmorphism was limited to bilateral pyelectasis and a prominent third ventricle. Spontaneous labor at 38 weeks resulted in the birth of a 3,570-gram AGA male with APGARs 71/85. The neonate had facial asymmetry, 5th finger clinodactyly, 2–3 toe syndactyly, undescended testicle, abnormal prepuce, and mild pyelectasis. CT scan revealed hypoplasia of the corpus callosum, while echocardiography demonstrated bicuspid aortic valve, and the neonatal karyotype (blood) returned 46,XY/47,XY+8. Evaluation at 3 months revealed more prominent facial asymmetry, plagiocephaly, plantar creases, descent of the testis, and mild developmental delay. Review of the literature does not include any previously reported maternal serum alpha-fetoprotein aberrations in mosaic trisomy 8.
Nonspecific Aerobic Vaginitis and Pregnancy
Authors: Čuržik Darko , Dražančić Ante , Hrgović Zlatko
Published: April 2003

During the period 1996–1998, cervical swabs of 50 pregnant women with subacute amniotic infection syndrome (AIS) and the semen of their consorts were bacteriologically analyzed. In the control group were 50 healthy pregnant women and their consorts too. Pathogenic bacteria (the most common were Escherichia coli, Staphylococcus haemolyticus, Chlamydia trachomatis and Ureaplasma urealyticum) were isolated from the cervical swab of 50 pregnant patients with AIS in 86.0% of them, while in the control group of healthy pregnant women in 28.0%. Pathogenic bacteria were present in 70.0% of semen of consorts pregnant women with AIS and only in 30.0% of semen of the control group. The congruity of pathogenic bacteria in the cervical swab and semen in the investigated group was 69.2%, while only 35.7% in the control group. Following erythromycin, cefuroxime and local tetracyclin treatment, the negativization of the cervical swab resulted in 30 pregnant patients with AIS, while the colonization persisted in 20 of them. The outcome of pregnancy was significantly better in cases with negativization of the cervical swab: perinatal loss was 6.7%, while in cases with persistent infection it was 55.0%. The authors presume the amniotic infection syndrome should be ascending manifestation of nonspecific vaginitis, which is maintained by the consort’s urogenital infection. AIS should be classified as a ‘sexually-transmitted disease’.
A Fetal Lung Lesion Consisting of Bronchogenic Cyst, Bronchopulmonary Sequestration, and Congenital Cystic Adenomatoid Malformation: The Missing Link?
Authors: MacKenzie Tippi C. , Guttenberg Marta E. , Nisenbaum Harvey L. , Johnson Mark P. , Adzick N. Scott
Published: April 2003

A fetus was found to have a large left thoracic cyst on routine prenatal ultrasound at 23 weeks of gestation. This lesion caused compression of the normal left lung tissue and contralateral mediastinal shift. At 23 weeks of gestation the cyst was percutaneously aspirated without subsequent reaccumulation of fluid. Serial ultrasounds showed decrease in the size of the cyst. The clinical diagnosis of congenital cystic adenomatoid malformation was made. At birth, the child had no respiratory distress, and a CT scan confirmed the finding of a fluid-filled cyst in the left chest. At the time of resection, a nonaerated extralobar bronchopulmonary sequestration (with a systemic arterial blood supply and separate pleural investment) was found. The dominant cyst had ciliated respiratory epithelium with cartilage, indicative of a bronchogenic cyst, and the remainder of the specimen had the histologic hallmarks of a congenital cystic adenomatoid malformation. The coexistence of three separate anomalies in one lesion suggests a common embryological link for these malformations.
Duplication Dup(1)(q32q44) Detected by Comparative Genomic Hybridization (CGH): Further Delineation of Trisomies 1q
Authors: Bartsch Christine , Aslan Mücevher , Köhler Jutta , Miny Peter , Horst Jürgen , Holzgreve Wolfgang , Rehder Helga , Fritz Barbara
Published: April 2003

Partial trisomy 1q is rare and mostly the result of an abnormal segregation of parental translocation chromosomes and their homologues. Only 31 cases have been described with pure partial trisomy 1q. In the fetus presented, chromosome analysis after amniocentesis had shown an unbalanced male karyotype with an aberrant chromosome 1. A de novo terminal duplication of the long arm was suspected but could not be verified by FISH in 1994. Five years after fetal death, retrospective identification of the additional material in 1q could finally be achieved by comparative genomic hybridization (CGH) using DNA extracted from formalin-fixed and paraffin-embedded fetal tissues. A direct duplication dir dup (1)(pter→q44::q32.1→qter) was found. Only 6 other individuals with duplication of this segment have been described so far. Comparative delineation of a dup1q phenotype with regard to size and origin of the dup (1q) segment evidenced that large duplications as well as proximal and interstitial duplications coincide with more severe visceral malformations, severe mental retar- dation and a short life span. Terminal duplications (1q32→qter) concur with less severe malformations and longer periods of survival, but marked mental retardation. With small terminal duplications (1q42→qter) dysmorphisms are usually mild and intellectual performance is mostly in the normal range.
Fetal and Maternal White Cells andB- and T-Lymphocyte Subpopulations in Pregnant Women with Recent Infection
Authors: Poblete Andres , Roberts Alistair , Trespidi Laura , Guarneri Daniela , Bonati Francesca , Nicolini Umberto
Published: April 2003

Objective: To study maternal and fetal white cell counts, B- and T-lymphocyte subpopulations in pregnant women with evidence of recent infection. Methods: Thirty-seven pregnant women with recent infection and 38 controls were studied. All were referred for fetal blood sampling to exclude congenital infection, or to perform fetal chromosome analysis. There were 16 infected fetuses: 9 cytomegalovirus (CMV), 4 rubella, and 3 toxoplasmosis. Maternal and fetal blood was taken and white cell counts, the percentage of CD3+, CD4+, CD8+, CD56+, HLADR+CD3+ T-lymphocyte subpopulations and CD19+ B lymphocytes were measured. Results: The percentage of CD3+, CD8+ , and HLADR+CD3+ lymphocytes were significantly higher in infected mothers compared to controls, while CD19+ and the CD4+/CD8+ ratio were lower. Infected mothers carrying infected fetuses had significantly lower white blood cell counts compared to those infected mothers without fetal infection. The percentage of HLADR+CD3+ T lymphocytes was significantly higher and the CD4+/CD8+ ratio lower in infected fetuses compared to controls and noninfected fetuses of infected mothers. Abnormal CD4+/CD8+ ratios and/or increased HLADR+CT3+ T lymphocytes were found in 8 of 10 fetuses with structural abnormalities and/or hematological/biochemical signs of systemic damage, and in 7 of 27 without (RR = 3.1, 95% CI = 1.5–6.3). Conclusion: Both infected fetuses and their mothers have significant identifiable changes in white cell counts and T-lymphocyte subpopulations compared to controls. These tests may help in diagnosing maternal and fetal infection.
Time-Related Effects of Cytomegalovirus Infection on the Development of Chronic Renal Allograft Rejection in a Rat Model
Authors: Lautenschlager Irmeli , Soots Anu , Krogerus Leena , Inkinen Kaija , Kloover Jeroen , Loginov Raisa , Holma Kaisa , Kauppinen Harri , Bruggeman Cathrien , Ahonen Juhani
Published: April 2003

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.
Human Cytomegalovirus Infection of Immature Dendritic Cells and Macrophages
Authors: Jahn Gerhard , Stenglein Stephan , Riegler Susanne , Einsele Hermann , Sinzger Christian
Published: April 2003

A central aspect of human cytomegalovirus (HCMV) pathogenesis is the interaction of the virus with different antigen-presenting cell (APC) types of the host. In principle, a number of various cell types have the potential of antigen presentation when MHC II expression is induced by appropriate stimuli. The most potent antigen presenters are monocytes/macrophages and dendritic cells (DCs), therefore called professional APCs. Interestingly, these cells seem to be targets of productive HCMV infection. The susceptibility of the monocyte/macrophage system has been analyzed intensively during the past decade. Investigation of the role of DCs during HCMV infection, however, has begun only recently.
Alphavirus Vectors: Applications for DNA Vaccine Production and Gene Expression
Authors: Lundstrom Kenneth
Published: April 2003

Replication-deficient alphavirus vectors have been developed for efficient high-level transgene expression. The broad host range of alphaviruses has allowed infection of a wide variety of mammalian cell lines and primary cultures. Particularly, G protein-coupled receptors have been expressed at high levels and subjected to binding and functional studies. Expression in suspension cultures has greatly facilitated production of large quantities of recombinant proteins for structural studies. Injection of recombinant alphavirus vectors into rodent brain resulted in local reporter gene expression. Highly neuron-specific expression was obtained in hippocampal slice cultures in vivo. Additionally, preliminary studies in animal models suggest that alphavirus vectors can be attractive candidates for gene therapy applications. Traditionally alphavirus vectors, either attenuated strains or replication-deficient particles, have been used to elicit efficient immune responses in animals. Recently, the application of alphaviruses has been extended to naked nucleic acids. Injection of DNA as well as RNA vectors has demonstrated efficient antigen production. In many cases, protection against lethal challenges has been obtained after immunization with alphavirus particles or nucleic acid vectors. Alphavirus vectors can therefore be considered as potentially promising vectors for vaccine production.
Suppression of ICAM-1 Expression in Renal Proximal Tubular Cells by 1,25-Dihydroxyvitamin D3
Authors: Weinreich Thomas , Wüthrich Rudolf P. , Booy Christa , Binswanger Ulrich
Published: April 2003

Background: 1,25-Dihydroxyvitamin D3 is mainly synthesized by renal proximal tubular cells. More recently, it has been shown to affect cell growth and TGF-β1 synthesis in glomerular and tubular renal cells in vitro, and to prevent glomerulosclerosis in vivo in subtotally nephrectomized rats. The mechanisms involved have not been fully identified. We asked whether 1,25-vitamin D3 might interact with additional immunoregulatory functions of renal cells by studying its effects on the expression of the cellular adhesion molecules ICAM-1 (CD54) and VCAM-1 (CD106) in human proximal tubular cells in vitro (HK-2 cells). Methods: Expression of adhesion molecules was assessed in HK-2 cells cultured under basal conditions and after stimulation with TNF-α plus IFN-γ, by flow cytometry, gene transcription (RT-PCR) and measurement of soluble ICAM-1 in culture supernatant by ELISA. Results: Unstimulated HK-2 cells did not express VCAM-1 and only little ICAM-1. 1,25-Vitamin D3 had no effect on the expression of adhesion molecules in unstimulated cells. TNF/IFN stimulation resulted in a 4-fold increase in ICAM-1 and VCAM-1 expression. The TNF/IFN-induced increase in ICAM-1 expression was reduced by 1,25-vitamin D3 dose dependently (10–7 M vs. solvent: –30%; 10–9 M: –18%; 10–11 M: –17%). 25(OH)-vitamin D3 had no effect. ICAM-1 mRNA concentration was increased in TNF/IFN-stimulated cells. 1,25-Vitamin D3 treatment prevented the increase of ICAM-1 mRNA by 27% after 24–72 h incubation (p = 0.03). The TNF/IFN-induced increase in soluble ICAM in culture supernatants was unchanged by 1,25-vitamin D3. VCAM-1 expression was unchanged by incubation with 1,25-vitamin D3 under basal conditions and after TNF/IFN stimulation. Conclusion: 1,25-Vitamin D3 inhibits cytokine-induced ICAM-1 but not VCAM-1 expression in renal proximal tubular cells in vitro. The present data support the hypothesis that 1,25-vitamin D3 is not only synthesized by renal tubular cells, but may also affect immunoregulatory functions in these cells.
Intrarenal Distribution of Blood Flow in Sodium Depleted and Sodium Loaded Rats: Role of Nitric Oxide
Authors: Hably Csilla , Vág János , Tost Hilda , Csabai Zsuzsanna , Bartha Jenő
Published: April 2003

The renal hemodynamic effects of nitric oxide synthase (NOS) inhibition and dietary salt were studied in rats. L-NAME (0.1 mg/ml in the drinking fluid, about 12 mg/kg/day) was given for 4 days to rats receiving low (sodium depletion, SD), normal (N) or high (sodium load, SL) NaCl diet. Intrarenal hemodynamics was studied in anaesthesia. NOS inhibition decreased renal blood flow and increased renal vascular resistance in each group. Cortical and outer medullary but not inner medullary blood flow increased in direct ratio to the sodium intake. NOS inhibition decreased the blood flow and increased the vascular resistance in all layers of the kidney in SD, N, and SL rats as well. In SD and N, but not in SL rats L-NAME induced vasoconstriction was higher in the outer (OM) and inner medulla (IM) than in the cortex (C) [SD: ΔCVR 43%, ΔOMVR 54%, ΔIMVR 84%; N: ΔCVR 54%, ΔOMVR 96%, ΔIMVR 106%; SL: ΔCVR 50%, ΔOMVR 64%, ΔIMVR 35%]; in normal rats blood flow shifts from the medulla toward the cortex. In conclusion, nitric oxide may have a role in the regulation of renal vascular tone not only in the case of regular sodium uptake but in the sodium depleted or loaded organism as well. However, nitric oxide has no role in the dietary salt evoked vascular adaptation in the kidney.
Studies of the Relationship between Allergen-Specific IgE Antibodies and Skin Test Reactivity in Patients with Asthma in Kuwait
Authors: Khadadah M.E. , Onadeko B.O. , Ezeamuzie C.I. , Maroof R. , Mustafa H.S. , Sugathan T.N.
Published: April 2003

Background: Studies have shown that allergens are important sensitizing agents in asthma. The relationship between various allergy markers has not been documented in Kuwait, although asthma is common. This study was therefore designed to investigate this relationship. Method: One hundred and one adult asthmatics were recruited over a 1-year period for this study. After administering a skin prick test (SPT) for common allergens, blood was taken for measuring specific IgE concentrations. Results: Eighty-two percent of the patients had positive SPT reactions to at least one allergen. Chenopodium sensitization was the most common, occurring in 47% of cases. Specific IgE was positive in fewer cases, which showed a positive reaction to SPT with the same allergen, the highest being observed with cockroach, occurring in 76% of the cases. There was a positive correlation between the wheal diameter of SPT and the concentration of specific IgE in three of the four allergens tested (r = 0.376, p ≤ 0.001 for Bermuda grass; r = 0.255, p ≤ 0.01 for cockroach, and r = 0.254, p ≤ 0.01 for chenopodium). The sensitivity, specificity and diagnostic accuracy of SPT in the allergens tested were below the reported findings in studies from Western countries. Conclusion: This study revealed that SPT had a better predictive value than specific IgE, and there was evidence of increasing sensitization to the cockroach allergen in this environment.
Passage of Interleukin-1-Beta Across the Blood-Brain Barrier Is Reduced in Aged Mice: A Possible Mechanism for Diminished Fever in Aging
Authors: McLay Robert N. , Kastin Abba J. , Zadina James E.
Published: April 2003

Objective: Cytokine signaling is the key to fighting infection. Fever is elicited by the production of inflammatory cytokines, particularly interleukin-1β (IL-1β), and the subsequent action of cytokines in the hypothalamus. In old age, the ability to produce fever in response to infection or to peripheral injections of IL-1β is diminished. Intracerebroventricular injections of IL-1β can still produce a normal fever response in the aged. A logical hypothesis to explain this discrepancy is that passage of IL-1β across the blood-brain barrier (BBB) is altered. Method: We used a quantitative in vivo technique, which previously showed a saturable system transporting IL-1β across the BBB, to investigate the speed at which radiolabeled IL-1β crosses from blood to brain in mice of widely different ages. Results: We found that passage of IL-1β across the BBB was significantly decreased in old (23-month) mice as compared with young (2-month) or middle-aged (12-month) animals. Passage of IL-1β across the blood-testis barrier was not significantly different among the groups. The passage of radiolabeled albumin across the BBB was not increased in any group, ruling out any disruption of the BBB by IL-1β. Conclusion: These results provide a mechanism that could help explain why fever production is reduced in old age and suggest an important role for the BBB in regulating immune changes.
Differential Management of Ca2+ Oscillations by Anterior Pituitary Cells: A Comparative Overview
Authors: Kwiecien Renata , Hammond Constance
Published: April 2003

Most electrical and ionic properties of anterior pituitary cells are common to all pituitary cell types; only gonadotropes exhibit a few cell specific features. Under basal conditions, the majority of pituitary cells in vitro, irrespective of their cell type, display spontaneous action potentials and [Ca2+]i transients that result from rhythmic Ca2+ entry through L-type Ca2+ channels. The main function of these action potentials is to maintain cells in a readily activable responsive state. We propose to call this state a ‘pacemaker mode’, since it persists in the absence of extrinsic stimulation. When challenged by hypothalamic releasing hormones, cells exhibit two distinct response patterns: amplification of pacemaker activity or shift to internal Ca2+ release mode. In the internal Ca2+ release mode, [Ca2+]i oscillations are not initiated by entry of external Ca2+, but by release of Ca2+ from intracellular stores. In somatotropes and corticotropes, GHRH or CRH triggers the pacemaker mode in silent cells and amplifies it in spontaneously active cells. In contrast, in gonadotropes GnRH activates the internal Ca2+ release mode in silent cells and switches already active cells from the pacemaker to the internal Ca2+ release mode. Interestingly, homologous normal and tumoral cells display the same type of activity in vitro, in the absence or presence of hypothalamic hormones. Pacemaker and internal Ca2+ release modes are likely to serve different purposes. Pacemaker activity allows long-lasting sequences of [Ca2+]i oscillations (and thus sustained periods of secretion) that stop under the influence of hypothalamic inhibitory peptides. In contrast, the time during which cells can maintain internal Ca2+ release mode depends upon the importance of intracellular Ca2+ stores. This mode is thus more adapted to trigger secretory peaks of large amplitude and short duration. On the basis of these observations, theoretical models of pituitary cell activity can be proposed.
Melatonin Modulation of the Daily Prolactin Secretion in Intact and Ovariectomized Ewes
Authors: Misztal Tomasz , Romanowicz Katarzyna , Barcikowski Bernard
Published: April 2003

The aim of this study was to investigate whether melatonin might modulate the daily prolactin secretion in the ewe during a period of ovarian activity and, if so, whether this modulatory action of melatonin was related to the presence of estradiol in the organism. Ewes in the late follicular and luteal phase, as well as overiectomized ewes without (OVX) and after 7 days of estradiol injections (OVX+E2) were examined. Melatonin was infused into the third brain ventricle (100 µg/100 µl/h) from 14.00 to 18.00 h. The concentration of prolactin increased significantly during the infusion of melatonin in late follicular-phase ewes, but not in luteal-phase ewes, as compared to the concentration before the infusion: range from 204.0 ± 31.7 to 272.2 ± 50.1 ng/ml vs. range from 68.2 ± 31.8 to 94.7 ± 33.1 ng/ml (mean ± SEM, n = 4, p < 0.01) and to the concentration noted during control infusions: range from 130.0 ± 58.0 to 179.3 ± 55.6 ng/ml (mean ± SEM, n = 4, p < 0.05). In ovariectomized ewes, the concentration of prolactin during infusion of melatonin increased significantly, unrelated to the presence of estradiol, as compared to the concentration before infusion: range from 136.7 ± 20.3 to 260.0 ± 11.6 ng/ml vs. range from 41.6 ± 2.6 to 152.3 ± 14.6 ng/ml in OVX ewes (mean ± SEM, n = 4, p < 0.01) and range from 161.5 ± 66.5 to 250.2 ± 24.3 ng/ml vs. range from 61.2 ± 1.7 to 159.2 ± 43.3 ng/ml in OVX+E2 ewes (mean ± SEM, n = 4, p < 0.01). Concentrations during infusion of melatonin in OVX and OVX+E2 ewes were also significantly higher than during the control infusions: range from 7.2 ± 1.7 to 22.2 ± 4.1 ng/ml (mean ± SEM, n = 4, p < 0.001). These results indicate that melatonin may affect the daily secretion of prolactin in ewes during the breeding season, and suggest that the variable response of prolactin to the melatonin signal in intact and ovariectomized ewes relates to the interaction between both ovarian steroids – estradiol and progesterone – and the prolactin-releasing factor.
Effects of Leptin on Melanin-Concentrating Hormone Expression in the Brain of Lean and Obese Lepob/Lepob Mice
Authors: Huang Qingling , Viale Agnès , Picard Frédéric , Nahon Jean-Louis , Richard Denis
Published: April 2003

The effect of leptin on the expression of melanin-concentrating hormone (MCH) was investigated in lean and genetically obese Lepob/Lepob mice. Murine leptin was subcutaneously infused using osmotic minipumps. The treatment period extended to 7 days and the daily dose of leptin delivered was 100 µg/kg of body weight. In situ hybridization was used to assess the effects of leptin infusion on the expression of MCH mRNA. MCH levels in the brain (hypothalamus/thalamus and the remaining part), spleen and testis were measured by radioimmunoassay coupled to HPLC of selected tissue extracts. Leptin significantly reduced final body weight, weight of brown adipose tissue, daily food intake in obese mice but not in lean animals. In obese mice, leptin led to a rapid reduction in food intake which reached statistical significance after only 24 h and which led to a significant reduction in the body weight after 3 days of treatment. Leptin restored the normal circulating levels of glucose and insulin in obese mice. The present results mainly provide evidence for a stimulating effect of leptin infusion on the MCH neuronal system. The hypothalamic/thalamic levels of MCH mRNA and peptide were higher in mice treated with leptin than in mice infused with phosphate-buffered saline. The stimulation of MCH neurons appeared particularly intense in obese mice, in which the effects of leptin infusion led to the reduction in MCH content of neuron fibers and terminals. Leptin did not affect spleen and testis MCH contents. In the light of the acknowledged orexigenic effects of MCH, the results of this study questioned the direct role of MCH in the action of leptin on energy balance. The increase in MCH expression following leptin could occur as a mechanism to compensate the decrease in energy deposition led to by leptin. It may also indicate that MCH mediates the metabolic actions of leptin indirectly or else that leptin influences actions of MCH other than those related to the regulation of energy balance.
Central Administration of Antiserum to Vasoactive Intestinal Peptide Delays and Reduces Luteinizing Hormone and Prolactin Surges in Ovariectomized, Estrogen-Treated Rats
Authors: vanderBeek ElineM. , Swarts HansJ.M. , Wiegant VictorM.
Published: April 2003

The present study investigated the role of hypothalamic VIP in the regulation of the LH and PRL surge using immunoneutralization of endogenous VIP in mature ovariectomized (OVX), estradiol benzoate (EB)-treated female Wistar rats. We compared the effect of intracerebroventricular (i.c.v.) injections of a VIP antiserum (VIP-Ab) with that of saline (Ctr) on LH and PRL profiles in two separate groups of rats following two subcutaneous EB injections on days 8 and 9 after OVX. VIP-Ab or Ctr injections were given during the second half of the dark period, i.e. at 22:00 h (day 9), and, in addition, the following morning, i.e. at 08:00 h (day 10), just before the expected onset of the LH surge. Hourly blood samples were collected between 09:00 and 18:00 h on day 10. In addition, we studied the reproducibility of EB-induced LH and PRL surges and compared the effect of Ctr and VIP-Ab treatment on sequential surges in individual OVX females, i.e. 10 and 23 days after OVX, using each animal as its own control. Although we observeda large variation in the height and timing of LH and PRL peak levels between EB-treated females, the characteristics of successive surges of individual rats were highly reproducible. This reproducibility suggests that differences in functioning of the suprachiasmatic nucleus as well as in the response of the hypothalamus to steroid feedback largely explain the normal variation in hormone responses between rats. The VIP-Ab treatment resulted in a significant delay in the time course and a strong reduction of the magnitude of the afternoon LH and PRL surge. When analyzed within individual females, the effect of VIP-Ab treatment was even more pronounced due to a reduction in variability when each animal was used as its own control. These results suggest that hypothalamic VIP is an important regulator of both the timing and the magnitude of the EB-induced LH and PRL surge in the OVX rat, and suggest that its role may be stimulatory in this respect.
Restricted Presence of the Growth Hormone-Releasing Hormone Receptor to Somatotropes in Rat and Human Pituitaries
Authors: Morel Gérard , Gallego Rosalia , Boulanger Luce , Pintos Elena , Garcia-Caballero Tomás , Gaudreau Pierrette
Published: April 2003

Specific binding of growth hormone-releasing hormone (GHRH) to its plasma membrane receptor represents the first step of cellular signals leading to exocytotic GH secretion in the anterior pituitary. The GHRH receptor (GHRH-R) has been cloned and belongs to the secretin/glucagon/vasoactive intestinal peptide subfamilly of G-protein-coupled receptors. To study its characteristics in rat and human pituitaries and examine its cellular and subcellular localization, a site-directed polyclonal antibody recognizing the C-terminal portion 392–404 of the rat and human GHRH-R was used. Immunohistochemistry was performed on paraffin-embedded pituitary sections while ultrastructural immunocytology was done on frozen and Lowicryl-resin-embedded ultrathin sections. GHRH-R-like immunoreactivity was restricted to somatotropes and colocalized with GH in both rat and human tissues. No signal was detected in gonadotropes, lactotropes, corticotropes and thyrotropes. At the subcellular level, gold particles were associated with the plasma membrane (observed on ultrathin frozen sections), secretory granule membrane, cytoplasmic matrix, nuclear membrane and nuclear matrix. In the nucleus, gold particles were mainly observed at the junction between eu- and heterochromatin. The highest density of labeling was observed in the cytoplasm (55 vs. 45% in the nucleus), mainly in secretory granules (59% of cytoplasmic labeling) and the plasma membrane. These results support the hypothesis that GHRH-mediated actions in the pituitary are specific to somatotropes and that GHRH-R isoforms and/or ligand-receptor complexes are involved in intracellular trafficking, recycling processes and nuclear functions.
Noradrenergic and Dopaminergic Activity in the Hypothalamic Paraventricular Nucleus after Naloxone-Induced Morphine Withdrawal
Authors: Fuertes Gregorio , Laorden M. Luisa , Milanés M. Victoria
Published: April 2003

Previous research has shown an increase in hypothalamo-pituitary-adrenal axis activity following naloxone administration to morphine-dependent rats. In the present study, we investigated the adaptive changes in the noradrenaline (NA) and dopamine (DA) systems in the hypothalamic paraventricular nucleus (PVN) during morphine dependence and withdrawal. Additionally, we examined the possible change in 3′,5′-cyclic adenosine monophosphate (cAMP) levels in that nucleus under the same conditions. Rats were made dependent on morphine by morphine or placebo (naïve) pellet implantation for 7 days. On day 8, rat groups received an acute injection of saline or naloxone (1 mg/kg subcutaneously) and were decapitated 30 min later. NA and DA content as well as their metabolite production in the PVN were estimated by HPLC/ED. Both plasma corticosterone levels and cAMP concentration in the PVN were measured by RIA. Naloxone administration to morphine-dependent rats (withdrawal) induced a pronounced increase in the production of both the NA metabolite MHPG and the DA metabolite DOPAC and an enhanced NA and DA turnover. Furthermore, an increase in corticosterone secretion was observed in parallel to the changes in catecholamine turnover. However, no alterations in cAMP levels were seen during morphine withdrawal. These results raise the possibility that catecholaminergic afferents to the PVN could play a significant role in the alterations of PVN functions and consequently in the pituitary-adrenal response during morphine abstinence syndrome. These data provide further support for the idea of adaptive changes in catecholaminergic neurons projecting to the PVN during chronic morphine exposure.
Sex- and Age-Related P75 Neurotrophin Receptor Expression in the Human Supraoptic Nucleus
Authors: Ishunina Tatjana A. , Salehi Ahmad , Swaab Dick F.
Published: April 2003

The human supraoptic nucleus (SON) is the main production site of plasma vasopressin. Previously, using the Golgi apparatus and cell size as measures for neuronal metabolic activity, an activation of vasopressinergic neurons was found during ageing in the human SON in women but not in men. We hypothesized that the low-affinity neurotrophin receptor p75 (p75NTR) might be involved in the mechanism of activation of vasopressin neurons in postmenopausal women, since this receptor was found to be expressed in the SON neurons of aged individuals, and because p75NTR expression was shown to be suppressed by estrogens. Therefore, we investigated whether p75NTR immunoreactivity in the SON neurons was age- and sex-dependent. For this purpose, we studied paraffin sections of the SON in 32 postmortem brains of control patients ranging in age from 29 to 94 years with an anti-p75NTR antibody and determined the area of p75NTR immunoreactivity per neuron using an image analysis system. To study whether the p75NTR might also participate in the activation of SON neurons, we related Golgi apparatus size to the area of p75NTR immunoreactivity per cell in the same patients. We found that the area of p75NTR immunoreactivity per cell correlated indeed significantly with age and with Golgi apparatus size only in women but not in men. Therefore, our results suggest that p75NTR is involved in postmenopausal activation of vasopressinergic neurons in the human SON.
Prolactin Gene Disruption Does Not Compromise Differentiation of Tuberoinfundibular Dopaminergic Neurons
Authors: Phelps Carol J. , Horseman Nelson D.
Published: April 2003

In mice with spontaneous mutations in transcription factors Prop-1 or Pit-1, the pituitary fails to produce prolactin (PRL), GH and TSH, and numbers of hypothalamic PRL-regulating dopaminergic (DA) neurons (area A12) are reduced by more than 50%. A normal neuronal population can be maintained in these mutants by PRL treatment of neonates, but not of adults. Targeted disruption of the PRL structural gene in mice provides a new model of isolated PRL deficiency to test the specificity of the PRL neurotrophic effect. The present study used morphological methods to assess hypophysiotropic tuberoinfundibular dopaminergic (TIDA) neurons in these mice, with the hypothesis that isolated PRL deficiency also would lead to reduction in TIDA neuron number. Brains of female and male homozygous PRL-null (–/–) mice and normal heterozygous (+/–) siblings were compared using formaldehyde-induced endogenous catecholamine fluorescence and tyrosine hydroxylase (TH) immunocytochemistry. Immunostaining intensity was quantified using computerized image analysis, and total numbers of TH-immunoreactive neurons were counted in three diencephalic DA brain regions. Intensity of DA fluorescence in A12 perikarya and median eminence (ME) was reduced in –/– mice; fluorescence in other brain areas was comparable for –/– and +/– mice. Immunostaining intensity of TH was significantly lower (p = 0.0001) in –/– than in normal mice in perikarya of A12, but not in cell bodies of nonhypophysiotropic area A13 (medial zona incerta). In external ME, TH immunostaining intensity was lower (p = 0.0001) in PRL-null than in normal mice. The decrease in TH intensity in both perikarya and in ME was significant for both female and male –/– mice. However, numbers of A12 neurons in the PRL-null mice were not lower than those of normal siblings. TH-immunoreactive cell number also did not differ between +/– and –/– mice in areas A13 and periventricular A14. The presence of a normal complement of A12 DA neurons in the PRL-null mice, despite greatly reduced DA and TH, emphasizes that steady-state content and differentiation of phenotype in individual neurons are very different assessments. The results suggest that, although absence of the stimulatory PRL feedback signal results in diminished activity of TIDA neurons, differentiation of these cells is not adversely affected.
Leptin Receptor Immunoreactivity Is Present in Ascending Serotonergic and Catecholaminergic Neurons of the Rat
Authors: Hay-Schmidt Anders , Helboe Lone , Larsen Philip J.
Published: April 2003

Using double-labelling immunohistochemistry we have studied the localisation of leptin receptor proteins including both long and short forms and their possible presence in serotonergic (5-HT) and catecholaminergic neurons in the rat brain. Leptin receptor immunoreactivity was found to be widely distributed in the central nervous system including cortical areas, amygdala, several hypothalamic and thalamic nuclei, the raphe system, pontine nuclei, locus coeruleus, parabrachial nucleus, tractus solitarus and the medullary reticular formation. Serotonergic cell groups were identified by 5-HT immunocytochemistry and classified according to standard nomenclature. High degrees of co-existence of leptin receptor immunoreactivity with serotonin in the raphe system were observed in B1, B5, B6, B7, B8 and B9. In B3 and B2 less than 50% of the 5-HT cells colocalised leptin receptor immunoreactivity. Brainstem and diencephalic (catecholaminergic) neurons were identified by tyrosine hydroxylase immunocytochemistry and classified according to standard nomenclature. Within the periventricular hypothalamic dopaminergic nuclei A14 and A12, the metencephalic noradrenergic A6, A7, A2, A1, and the adrenergic C3, C2 and C1 cell groups, nearly all tyrosine hydroxylase-positive cells colocalised with leptin receptor immunoreactivity. In contrast, co-existence of tyrosine hydroxylase and leptin receptor immunoreactivities in the dopaminergic A13, A11, A10, A9 and A8 cell was practically non-existent. Thus leptin, the adipose tissue-derived ligand of the leptin receptor, may in some brain areas directly influence serotonergic, dopaminergic, adrenergic and noradrenergic inputs to the periventricular and medial hypothalamic nuclei.