bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Release and Determination of Subtype of Porcine Endogenous Retroviruses Produced by Stimulated Normal Pig Blood Cells
Authors: Tacke Stefan J. , Specke Volker , Denner Joachim
Published: April 2003

Objective: Porcine endogenous retroviruses (PERVs) are of particular concern with xenotransplantations using pig cells, tissues or organs as they are present in the genome of all pig strains and are able to infect human cells in vitro. However, it remains unclear whether PERV particles will be produced in vivo and whether they may infect xenotransplant recipients. Since normal pig peripheral blood mononuclear cells (PBMCs) may be transmitted together with the transplanted organ, the production of PERVs by stimulated PBMCs was studied in vitro. Methods: To simulate antigen-induced activation of PBMCs, phytohaemagglutinin (PHA), a T cell mitogen, and the phorbol ester O-tetradecanoylphorbol-13-acetate (TPA), a tumour promoter, were used. Virus release was estimated by measuring reverse transcriptase (RT) activity and by RT-PCR of pelleted viruses. Results: Treatment of pig PBMCs with PHA or TPA induced the release of PERVs. For the first time, a correlation between the extent of proliferation of pig PBMCs and PERV production was shown. In addition, PERV release by non-proliferating cells and differences in virus production between stimuli as well as between different pig strains and individuals of one strain were observed. Subtype analysis revealed the release of the three subtypes PERV-A, PERV-B and PERV-C. In contrast to murine endogenous retroviruses, PERVs were induced by PHA alone. Conclusion: The data suggest that the PBMCs transmitted within a xenotransplant may release PERV. These data also suggest that pig strains producing low amounts of virus could be more suitable for xenotransplantation.
Ethical Issues in Organ Transplantation
Authors: Abouna George M.
Published: April 2003

Clinical organ transplantation has been recognized as one of the most gripping medical advances of the century as it provides a way of giving the gift of life to patients with terminal failure of vital organs, which requires the participation of other fellow human beings and of society by donating organs from deceased or living individuals. The increasing incidence of vital organ failure and the inadequate supply of organs, especially from cadavers, has created a wide gap between organ supply and organ demand, which has resulted in very long waiting times to receive an organ as well as an increasing number of deaths while waiting. These events have raised many ethical, moral and societal issues regarding supply, the methods of organ allocation, the use of living donors as volunteers including minors. It has also led to the practice of organ sale by entrepreneurs for financial gains in some parts the world through exploitation of the poor, for the benefit of the wealthy. The current advances in immunology and tissue engineering and the use of animal organs, xenotransplantation, while offering very promising solutions to many of these problems, also raise additional ethical and medical issues which must be considered by the medical profession as well as society. This review deals with the ethical and moral issues generated by the current advances in organ transplantation, the problem of organ supply versus organ demand and the appropriate allocation of available organs. It deals with the risks and benefits of organ donation from living donors, the appropriate and acceptable methods to increase organ donation from the deceased through the adoption of the principle of ‘presumed consent’, the right methods of providing acceptable appreciation and compensation for the family of the deceased as well as volunteer and altruistic donors, and the duties and responsibilities of the medical profession and society to help fellow humans. The review also deals with the appropriate and ethically acceptable ways of utilizing the recent advances of stem cell transplantation from adult versus fetal donors, tissue engineering and the use of organs from animals or xenotransplantation. Data provided in support of the concept that clinical organ and tissue transplantation can be more beneficial and life saving if everyone involved in the process, including physicians and medical institutions, respect and consider the best interests of the patients, as well as honor the ethical, moral and religious values of society and are not tempted to seek personal fame or financial rewards.
Nasogastric Tube Syndrome: The Unilateral Variant
Authors: Nehru Vikas Inder Nath , Al Shammari Hussein Jasser , Jaffer Abdul Mohsen
Published: April 2003

Nasogastric tube syndrome is an uncommon but a potentially life-threatening complication of nasogastric intubation. It presents as an acute upper airway obstruction secondary to bilateral abductor vocal cord dysfunction resulting from postcricoid chondritis. However, a unilateral variant has also been reported and may herald the development of bilateral pathology. The purpose of this report is to highlight early warning signals of impending crisis. Clinical Presentation: A case of unilateral vocal cord involvement secondary to postcricoid chondritis resulting from nasogastric intubation is presented. An additional feature, not reported previously, is the presence of two inflammatory nodular swellings over the cricoid cartilage.
Vasovasostomy
Authors: Schroeder-Printzen I. , Diemer T. , Weidner W.
Published: April 2003

Vasovasostomy after sterilisation vasectomy is the most frequently performed microsurgical intervention in refertilizing surgery. Causes for obstruction other than vasectomy such as juvenile hernia repair and other kinds of surgery affecting the seminal cord appear to be rare. The pre-operative diagnostic approach follows the rules of conventional diagnostics in male infertility. The significance of the intra-operative evaluation of aspirates from the duct and its role in surgical decision-making is controversely debated in the literature. Similar controversies are evident concerning the microsurgical technique that is applied. In particular, the advantages of the two-layered technique (gold standard) of the anastomosis versus the single-layered technique are discussed. Other techniques such as laser applications and fibrin glue are not routinely used in humans. Even difficult microsurgical problems in cases with extended obstructions and cases of re-vasovasostomy can nowadays be managed and have significant success rates. Important prognostic factors appear to be the interval of obstruction, sperm granulomas, and length of the testicular end of the duct. High success rates accompanied by a lower profile in cost make the microsurgical approach (refertilization) superior versus the primary use of ART techniques such as ICSI.
Identification of a Novel Intercellular Structure in Late-Stage Differentiating Lens Cells
Authors: Dahm Ralf , Prescott Alan R.
Published: April 2003

This study describes a novel intercellular structure in the adult bovine lens. In differential interference contrast images, the structure has the shape of a thickened torus or ‘bagel’ of 3–9 µm in diameter and is contributed equally by 2 adjacent fibre cells. Due to its shape and location reaching into 2 neighbouring cells, the novel structure was termed ‘intercellular torus’ or ‘bagel’. Intercellular bagels are present in a subset of late-stage lens fibre cells of the intermediate cortex, a considerable time after the cytoplasmic organelles have been broken down and the pyknotic nuclear remnants have disappeared. They are not present in deeper fibres. Our experiments show that intercellular bagels do not stain positive for DNA or RNAs, but are rich in lipids. Preliminary data indicate that the intercellular bagels contain calcium, suggesting that they might act as a place of transient Ca2+ storage or sequestration after the intracellular organelles, such as the endoplasmatic reticulum, nuclear envelope, Golgi apparatus and mitochondria have been eliminated from the lens fibres during terminal differentiation.
Augmentation of Galactose-Specific Glycoproteins during Corneal Epithelial Migration in Organ Culture
Authors: Asifa Ahmed , Nikhat Ahmed
Published: April 2003

The purpose of the present study was to identify galactose-specific glycoproteins that are synthesized in higher amounts or downregulated during the migratory process of corneal epithelium. Trichloroacetic-acid-precipitable proteins showed an increased incorporation of 3H-galactose with time in migrating corneal epithelium in organ culture. Galactose oxidase treatment of immobilized 3-[(3-cholamidopropyl)dimethylamminio]-1-propanesulfonate-extractable glycoproteins of migrating and nonmigrating corneal epithelia resolved on sodium dodecylsulfate polyacrylamide gel electrophoresis was carried out. Two prominent terminally galactosylated protein bands (180 and 98 kD) were seen in the migrating epithelium but were absent in the nonmigrating epithelium. We conclude that during the migratory process of the corneal epithelium there is an increased utilization of galactose, and galactose-specific glycoproteins are synthesized in higher amounts.
Radiographic Dentinal Caries and Its Progression in Occlusal Surfaces in Dutch 17-Year-Olds: A 6-Year Longitudinal Study
Authors: Poorterman Jan H.G. , Weerheijm Karin L. , Aartman Irene H.A. , Kalsbeek Huib
Published: April 2003

In this study, the status of 705 occlusal surfaces of first and second molars of 90 17-year-olds was analysed longitudinally in a 6-year follow-up, using a combination of clinical and radiographic information. Clinical data were derived from an epidemiological project. Each of two examiners judged all bitewing radiographs. The overall Cohen’s ĸ for interexaminer agreement of radiographic assessments was 0.77. Between the age of 17 and 23 years, about one third of sound occlusal surfaces developed a new dentinal radiolucency, and over 70% of existing radiolucencies showed progression, both irrespective of the presence of a sealant. In both examination years, almost 20% of the restored surfaces showed signs of a dentinal radiolucency. It was concluded that at the age of 17 occlusal surfaces are still highly susceptible to new dentine caries and further progression of dentinal radiolucencies already present.
Demineralization of Er:YAG and Er,Cr:YSGG Laser-Prepared Enamel Cavities in vitro
Authors: Apel C. , Schäfer C. , Gutknecht N.
Published: April 2003

The aim of the present study was to establish whether cavity preparation by means of an erbium laser with efficient water cooling is capable of reducing the susceptibility of the prepared dental enamel to demineralization and thus of achieving a potential caries-protective effect in the region of cavity margins. To this end, cavities limited to the enamel were prepared in the crowns of 10 teeth each using an Er:YAG (λ = 2,940 nm) and an Er,Cr:YSGG laser (λ = 2,780 nm). A control cavity prepared conventionally with a diamond drill in the same occlusal zone was assigned to each of these cavities. The specimens were then subjected to a pH-cycling caries model. Analysis was performed by quantitatively measuring the demineralization front under a polarized-light microscope. The results of the study showed that enamel cavities prepared with the erbium lasers used display a statistically significant acceleration of demineralization compared to conventionally prepared cavities (p < 0.01). The Er:YAG laser cavities revealed demineralization to a depth of 133.9 (SD 25.7) µm, while the value observed with the Er,Cr:YSGG laser was 133.8 (SD 25.8) µm. The depth of demineralization in the control groups was only 77.4 (SD 13.8) µm and 79.3 (SD 37.6) µm. No difference could be found between the two lasers (p = 0.98). Based on these in vitro tests, it cannot be assumed that use of the erbium laser for cavity preparation offers any advantages in terms of resistance to secondary caries in clinical practice.
Beneficial Effects of Intraperitoneally Administered Alpha-Tocopheryl Acetate on the Levels of Lipid Peroxide and Activity of Glutathione Peroxidase and Superoxide Dismutase in Skin, Blood and Liver of Thermally Injured Guinea Pigs
Authors: Lussi A. , Naziroglu M. , Francescut P. , Kökçam I. , Yilmaz Ş.
Published: April 2003

The aim of this study was to investigate the effects of intraperitoneal α-tocopheryl acetate administration on concentration of lipid peroxide (as malonyldialdehyde, MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma, red blood cells (RBC), skin and liver of thermally injured guinea pigs. MDA levels in the plasma, skin and liver were increased at the 15th min after the thermal injury compared to the control group. However, they were significantly lower in the α-tocopheryl-acetate-treated groups than both control and thermally injured groups from the 15th min to the 6th day. SOD activity of the skin and RBC and vitamin E levels in the plasma were significantly decreased between the 15th min and 6th day and then both parameters, i.e. SOD and vitamin E, were significantly increased by α-tocopheryl acetate administration. GSH-Px activity in the skin was also significantly decreased in groups from the 15th min to the 6th day, whereas it remained unchanged by the α-tocopheryl acetate administration. On the other hand, GSH-Px activity and GSH levels in the RBC remained the same during both thermal injury and α-tocopheryl acetate administration. In conclusion, we observed that the intraperitoneal administration of α-tocopheryl acetate protects the skin against thermal injury, which suggests that it may be due to the upregulation of enzymatic antioxidants.
Reactivity of Contact Allergenic Haptens to Amino Acid Residues in a Model Carrier Peptide, and Characterization of Formed Peptide-Hapten Adducts1
Authors: Ahlfors S.R. , Sterner O. , Hansson C.
Published: April 2003

The type of chemical reaction between hapten and carrier protein in the formation of a complete antigen in vivo giving rise to an allergic contact dermatitis (ACD, type IV allergy) is essentially unknown. About 4,000 low-molecular organic compounds are known to have allergenic properties. α,β-Unsaturated carbonyl structures are frequently present among these compounds. Haptens giving rise to antibody formation and type I allergy have been shown to add predominantly to lysine in the carrier protein. In this paper, the reactivity of activated type IV haptens to a model peptide is reported. Essentially all amino acids with nucleophilic properties were present in the model peptide. Investigation of the relative reactivities of the amino acid residues to activated haptens under biomimetic conditions is performed in order to determine the proportions between the adducts of the different amino acid moieties. In all cases, the electrophilic α,β-unsaturated haptens were found to be added to the cysteine residue and no lysine adduct was recorded. Nuclear magnetic resonance (NMR) spectroscopy was used to exclude steric hindrance of any amino acid residue in the addition reaction. The hapten-modified peptides were isolated and characterized by NMR and mass spectrometry.
Skin Penetration and Sun Protection Factor of Five UV Filters: Effect of the Vehicle
Authors: Chatelain E. , Gabard B. , Surber C.
Published: April 2003

To gain information about efficacy and safety of sunscreens, we compared the skin penetration of ultraviolet (UV) filters from two vehicles, i.e. an oil-in-water (O/W) emulsion gel and petrolatum jelly both in vitro and in vivo, as well as the corresponding pharmacological effect, i.e. the sun protection factor (SPF) in vivo. The UV filters studied were benzophenone-3 (BPH), ethylhexyl methoxycinnamate (EHM), butyl methoxydibenzoyl methane, ethylhexyl salicylate and homosalate. The human skin penetration of these five chemicals from the two vehicles was determined both in vitro using Franz cells and in vivo using a standardized tape-stripping method. The SPF of the two sunscreens was determined in vivo following the COLIPA guidelines. In vitro none of the filters permeated through the skin after 6 h of product application and very little could be found in the skin. BPH and EHM were the only UV filters found in the dermis (both after 30 min and 6 h). An effect of the vehicle could be noticed only for BPH after 30 min in the dermis and 6 h in both dermis and epidermis. In vivo, no differences in the amount of individual UV filters (in % of the applied dose) in the 15 first strips of the stratum corneum (SC) were found following 30 min of application of the formulations; however, the amount of UV filters that were retained in the SC was significantly higher (around 3 times) with the O/W emulsion gel than with the petrolatum jelly. This difference between the two vehicles was also of consequence for the SPF in vivo measured 30 min after application of the products (SPF ≅ 18 with the O/W emulsion gel compared to SPF ≅ 10 with the petrolatum jelly). By choosing the right vehicle or optimizing it, not only sunscreen products can be significantly improved in terms of pharmacological efficacy but the potential toxicological risk associated with the skin penetration of UV filters may be significantly reduced.
Temporal Bone Pathology in Syphilitic Osteitis
Authors: Suzuki Yukie , Ohtani Iwao , Ogawa Hiroshi , Baba Yoko , Suzuki Teruhisa , Kano Makoto
Published: April 2003

This study aimed at demonstrating the typical temporal bone histopathology of a 74-year-old female with syphilitic osteitis. There was osteitic fistulization between lateral semicircular canal and antrum and contact of the dilated saccular wall with the medial surface of the footplate. This case most likely would have had not only a positive fistula sign caused by fistulization, but also Hennebert’s sign caused by the contact of the saccular wall with the footplate.
Psychological Stress Increases Human T Cell Apoptosis in vitro
Authors: Sakami Shotaro , Nakata Akinori , Yamamura Takashi , Kawamura Noriyuki
Published: April 2003

Objectives: Recent studies have shown that apoptosis is involved in stress responses. The present study examined if stressors increase in vitro apoptosis of peripheral blood T lymphocytes in a dose-dependent manner. Methods: Daily subjective stress was quantitatively analyzed in 40 nonsmoking men with a daily hassles questionnaire. Apoptosis of T lymphocytes was measured by flowcytometry using Annexin V/PI double staining method after 0, 12, and 24 h of culture in the presence or absence of dexamethasone (DEX). Using a cross-sectional design, the current study examined the relationship between stress and in vitro apoptosis of T cells. Results: Results showed that apoptosis of T lymphocytes in vitro has a significant correlation with stress and age. Stress was positively correlated with percentage of apoptosis in T cells after 12 h of culture, irrespective of DEX treatment. Age was positively correlated with the percentage of T cell apoptosis after 0 and 12 h of coculture with DEX. Conclusions: These results indicate that age-related apoptosis and stress-related apoptosis of T cells are modulated through different mechanisms. This is the first study to show that in vitro lymphocyte apoptosis is influenced by daily stress in a dose-dependent manner.
Temperature-Induced Changes in Thyrotropin-Releasing Hormone Sensitivity in Carp Melanotropes
Authors: van den Burg Erwin H. , Metz Juriaan R. , Ross H. Alec , Darras Veerle M. , Wendelaar Bonga Sjoerd E. , Flik Gert
Published: April 2003

This study investigates whether thyrotropin-releasing hormone (TRH), α-melanocyte-stimulating hormone (α-MSH) and N-acetyl β-endorphin (NAc β-END), or the thyroid hormones thyroxine (T4) and 3,5,3′-triiodothyronine (T3) are involved in the physiological response to temperature changes in the poikilotherm common carp (Cyprinus carpio). Carps were either subjected to a rapid cold exposure or acclimated over time to three different temperatures. Acute cold exposure did not influence blood plasma α-MSH concentrations. Acclimation to 15, 22 or 29°C led to a temperature-dependent increase of both α-MSH and NAc β-END plasma concentrations. Moreover, the in vitro sensitivity to TRH of melanotrope cells (that synthesise these peptides) also correlated positively with ambient temperature. Increased TRH activation stimulated processing of the precursor of α-MSH and NAc β-END, resulting in increased release of both peptides and storage of a surplus of NAc β-END within melanotropes. Plasma T4 levels were highest in carps acclimated to the intermediate temperature tested, and correlated strongly with hypothalamic TRH content. Plasma T3 levels were unaffected by ambient water temperature. We conclude that ambient water temperature influences the sensitivity of melanotrope cells to TRH in carps. This effect, however, is not due to acute temperature change, but evolves during the acclimation process of carps to a new temperature.
Circadian Rhythms of Neuroendocrine Dopaminergic Neuronal Activity in Ovariectomized Rats
Authors: Sellix Michael T. , Freeman Marc E.
Published: April 2003

Prolactin (PRL) secretion is inhibited by dopamine (DA) released from hypothalamic neuroendocrine neurons designated tuberoinfundibular (TIDA), tuberohypophyseal (THDA) and periventricular hypophyseal (PHDA) dopaminergic (DAergic) neurons. Since PRL is secreted in many physiological states with a circadian rhythm, the purpose of these experiments was to determine if patterns of neuroendocrine DAergic neuronal activity in rats are also circadian. The activity of neuroendocrine DAergic neurons, defined as DA turnover rate in nerve terminals and quantitated as the ratio of DOPAC (a primary DA metabolite) to DA content, was measured by high-performance liquid chromatography with electrochemical detection (HPLC-EC) in these populations of DA neurons of OVX rats. TIDA neurons exhibit a rhythm of activity in a light:dark cycle which free-runs in constant dark (DD) and is entrained by light, indicating that TIDA neuronal activity is circadian. THDA and PHDA neurons also display daily rhythms entrained to a photoperiod and PHDA neuronal activity free-runs in DD with a period of approximately 24 h. However, a significant rhythm of THDA neuronal activity was not detected under DD. In the OVX rat, the activities of TIDA and PHDA neurons, but not THDA neurons, describe all the characteristics of a circadian rhythm as they are both entrained by light, but only TIDA and PHDA neurons maintain a significant rhythm of activity under DD.
In vivo Activation of the Interleukin-6 Receptor/gp130 Signaling Pathway in Pituitary Corticotropes of Lipopolysaccharide-Treated Rats
Authors: Gautron Laurent , Lafon Pierrette , Tramu Gérard , Layé Sophie
Published: April 2003

Adrenocorticotropic hormone (ACTH) release from anterior pituitary corticotropes is greatly increased during peripheral inflammation induced by lipopolysaccharide (LPS) administration. Interleukin-6 (IL-6) is thought to participate in LPS-induced ACTH release, but whether or not corticotropes are directly targeted by this cytokine is unclear. Therefore, we investigated the expression and activation of IL-6 signaling components in the pituitary of rats 2 and 4 h after administration of LPS (250 µg/kg). Intraperitoneal LPS treatment provoked the nuclear translocation of signal transducer and activator of transcription 3 (STAT-3) and Fos expression in the anterior pituitary lobe, as demonstrated by immunohistochemistry. By using in situ hybridization, we demonstrated that suppressor of cytokine signaling 3 (SOCS-3) and c-fos mRNAs were significantly induced by the LPS treatment in the anterior lobe of the pituitary. Dual in situ hybridization revealed that most corticotropes expressed IL-6 receptor and gp130 mRNAs, and that 2 h after LPS treatment, SOCS-3 and c-fos mRNAs were induced in corticotropes. Our results suggest that LPS-induced IL-6 could regulate the hypothalamo-pituitary-adrenal axis by directly targeting corticotropes during peripheral inflammation.
Lordosis of Rats Is Modified by Neurosteroidogenic Effects of Membrane Benzodiazepine Receptors in the Ventral Tegmental Area
Authors: Frye Cheryl A. , Petralia Sandra M.
Published: April 2003

Progestins modulate lordosis through actions in the ventral tegmental area (VTA). Whether neurosteroidogenesis of 5α-pregnan-3α-ol-20-one (3α,5α-THP), involving mitochondrial benzodiazepine receptors (MBR), is important for lordosis was investigated. Ovariectomized (Ovx), hormone-primed rats (experiments 1, 3, 5, 6) and rats in behavioral estrus (experiments 2 and 4) were unilaterally infused via chronic guide cannula to the VTA with a MBR agonist, N,N-dihexyl-2-(4-fluorophenyl) indole-30-acetamide (FGIN 1–27) or antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboximide (PK-11195). Experiment 1: Estradiol benzoate (EB)-primed (25 µg) rats administered 0 or 25 µg progesterone (P4) SC showed increased lordosis when infused with 5.0 µg FGIN 1–27 to the VTA; those administered 100 or 200 µg P4 SC exhibited greater lordosis when infused with 2.5 or 5.0 µg FGIN, relative to saline-infused rats. Experiment 2: Rats, near the termination of behavioral estrus, infused with 2.5 or 5.0 µg of FGIN 1–27 to the VTA, showed increased lordosis compared to that seen following vehicle administration. Experiment 3: EB-primed rats administered 200 or 500 µg P4 SC showed decreased lordosis when infused with 100, 200, or 400 ng PK-11195, relative to saline-infused rats. Experiment 4: Rats infused at the peak of behavioral estrus with 100, 200, or 400 ng PK-11195 to the VTA exhibited reduced lordosis compared to that seen following vehicle administration. Experiment 5: 3α,5α-THP (100 ng) infusions to the VTA reinstated lordosis of hormone-primed rats infused with PK-11195 (100 ng) to the VTA. Experiment 6: FGIN 1–27 (5.0 µg) and PK-11195 (100 ng) infusions aimed at the VTA respectively increased and decreased midbrain levels of 3α,5α-THP compared to vehicle. Notably, the specific effects observed with infusions to the VTA were not seen with infusions to the control site, the substantia nigra. These data suggest that neurosteroidogenesis involving MBRs in the VTA mediates lordosis of hormone-primed or behavioral estrous rats.
Differentiation between Fore- and Hindlimb Bones and Locomotor Behaviour in Primates
Authors: Kimura Tasuku
Published: April 2003

Primate appendicular limb bones were measured on the cross-sectional geometry at the mid-length of the humerus and femur and on the external dimensions of long bones of the same individuals. Cross sections were directly measured by means of computer tomography or direct sectioning. The morphometry of bones and locomotor behaviour is discussed from the viewpoint of the functional differentiation between the fore- and hindlimbs. The primate group which daily adopted a relatively terrestrial locomotor type demonstrates robust forelimb bones compared with the group which adopted a fully arboreal locomotor type. In contrast, the arboreal group showed relatively large and long hindlimb bones. The difference resembled the previously reported comparison between terrestrial and arboreal groups among wholly quadrupedal mammals. Humans were more similar to the arboreal group than to the terrestrial group. Parameters of the cross-sectional geometry showed a slightly positive allometry in total primate species. Slopes of the parameters were explained by the influence of muscle force.
Influence of Predicted FEV1 on Bronchodilator Response in Asthmatic Patients
Authors: Ouksel Hakima , Meslier Nicole , Badatcheff-Coat Anne , Racineux Jean-Louis
Published: April 2003

Background: There is currently disagreement on the way of expressing the reversibility of airflow obstruction, with some evaluations based on the initial FEV1 while others use predicted FEV1 (according to age, gender and height). Objectives: To test the relevance of expressing bronchodilator response as a percentage of predicted FEV1, we evaluated the influence of morphological data on the response to bronchodilators in a population with a large range of predicted values. Methods: We measured the change in FEV1 after inhalation of 200 µg of salbutamol in 30 asthmatic subjects (15 adults and 15 children) in whom predicted FEV1 ranged between 1.13 and 4.10 liters and analyzed the respective influence of initial and predicted FEV1 on bronchodilator response. Results: We have shown a significant relationship between the absolute variation in FEV1, in liters, and predicted FEV1 (p = 0.0019). There was also a significant relationship between the absolute variation in FEV1 and initial FEV1, in liters (p = 0.02). This relationship was no longer significant (p = 0.8) when the variation and initial FEV1 were both expressed as percentages of predicted FEV1. In addition, multiple regression analysis showed that predicted FEV1 was the only independent variable correlating with the response to bronchodilators. Conclusion: This study showed the influence of predicted FEV1 on bronchodilator response. This result provides an additional argument for expressing bronchodilator response as a percentage of predicted FEV1.
Pleural Effusion due to Histoplasma capsulatum and Idiopathic CD4 Lymphocytopenia
Authors: Kortsik C. , Elmer A. , Tamm I.
Published: April 2003

Acute histoplasmosis is usually a benign, self-limited infection in endemic areas. Since protection against Histoplasma capsulatum infection requires specific, cell-mediated immunity, histoplasmosis is well documented in patients with acquired T cell deficiencies e.g. due to HIV infection. We report here for the first time a case of pleural effusion due to H. capsulatum infection in a patient with idiopathic CD4 lymphocytopenia (ICL). A 25-year-old woman presented with chest pain, dyspnea on exertion and a moderate weight loss. Chest X-ray showed a large left pleural effusion, and thoracentesis yielded an exudate. Histologic examination of pleural biopsies identified H. capsulatum. Laboratory tests revealed lymphocytopenia with low CD4+ T cell counts (<100/µl) and a decreased CD4/CD8 ratio. Serology, including HIV, was repeatedly negative. The diagnosis of pleural effusion due to H. capsulatum infection in a patient with idiophatic ICL was established. There was no evidence of any other opportunistic infection. Treatment with itraconazole was initiated and pleural effusion resolved within 2 weeks of treatment. Moreover, the patient was found to have idiopathic thrombocytopenic purpura, as confirmed by the detection of autoantibodies against thrombocytes. In a 1-year follow-up, the patient remained asymptomatic without relapse or any new infection. Treatment with itraconazole was given for 12 months. Because of persistent CD4+ T cell counts below 100/µl, prophylactic antibiotic treatment is continued.
Severe Aplastic Anemia with Autoimmune Thyroiditis Showing No Hematological Response to Intensive Immunosuppressive Therapy
Authors: Tomonari Akira , Tojo Arinobu , Iseki Tohru , Ooi Jun , Hase Hidenori , Shirafuji Naoki , Tani Kenzaburo , Asano Shigetaka
Published: April 2003

A 39-year-old woman with severe aplastic anemia (SAA) was transferred to our institution. She also had autoimmune thyroiditis with several positive autoantibodies. Clonal or oligoclonal T-cell proliferation was demonstrated by determining the size distribution of the complementarity-determining region 3 (CDR3) of T-cell receptor β-chain (TCR-Vβ) subfamilies in the patient’s bone marrow and peripheral blood cells. The results suggested that hematopoiesis was suppressed by immune-mediated mechanisms. Immunosuppressive therapy for SAA using cyclosporin A (CsA) alone or concurrent CsA and antithymocyte globulin (ATG) failed to induce a hematological response. The intensity of the autoantibodies, however, partially decreased during this period. In addition, the CD4/CD8 ratio was inverted after immunosuppressive therapy. These observations indicate that, in a subset of SAA, immune-mediated hematopoietic suppression cannot be successfully treated by conventional immunosuppressive therapy, even though a substantial improvement in the underlying immunological changes can be achieved. Other therapies such as hematopoietic stem cell transplantation or more intensified repeated ATG therapy may be necessary for such patients.
Critical Periods of Eye Development in Vertebrates with Special Reference to Humans
Authors: Wu Yan , Lorke Dietrich Ernst , Lai Helen , Wai Sen Mun , Kung Lai Sin , Chan Wood Yee , Yew David Tai Wai
Published: April 2003

This review highlights similarities in human, rodent and avian eye development, focusing on morphogenesis, proliferative activity, apoptosis and mechanistic aspects during the development of the retina, the iris and the cornea. Retinal morphogenesis encompasses four stages: (1) appearance of the ganglion cell layer, (2) formation of the outer plexiform layer separating the inner and outer nuclear layers, (3) formation of immature photoreceptor segments and (4) development of outer photoreceptor segments. The first two stages occur very early during development, i.e. within the first 10 days of incubation in chickens, during the first postnatal week in rodents and until 28 weeks of gestation in humans. In contrast, the formation of receptor inner and outer segments takes considerably less time, i.e. about another 4 days in chickens, 7 days in rodents and 12 weeks in humans. Lesion experiments in chickens and rodents indicate that catecholaminergic input is a prerequisite for proper photoreceptor development, whereas synaptic contact of retinal ganglion cells with higher CNS centers is not necessary. Although already observed very early during the development of the human retina, apoptotic cell death only becomes significant after 23 weeks of gestation and further increases during late gestation. The majority of dying cells in the human and avian retina represent bipolar cells, and the number of apoptotic cells is highest during the formation of inner and outer photoreceptor segments. The similarities outlined in the present review indicate that the basic developmental mechanisms are the same in the primate, rodent and avian retina.
The Curious Genomic Path from Leaky Red Cell to Nephrotic Kidney
Authors: Stewart G.W. , Stewart G.W. , Fricke B. , Fricke B.
Published: April 2003

The human red cell has proved to be an invaluable model cell for the study of many aspects of membrane structure and function. It has a series of transport pathways which mediate the movements of the univalent cations Na and K, which are either identical or similar to systems in other human tissues, including the human kidney. The balance between the energy-consuming NaK pump and a ‘passive leak’ component maintains a net deficit of cations within the cell, which defends the cell volume against osmotic swelling. There exist a series of dominantly inherited human red cell conditions, gathered under the generic title ‘hereditary stomatocytoses’, in which the so-called ‘passive leak’ to Na and K is pathologically increased. In the more severe variants this compromises the integrity of the cell and the patients suffer haemolytic anaemia. Some less severe variants present with pseudohyperkalaemia caused by loss of K from red cells on storage of blood at room temperature. The most severe variants show a deficiency in a widely distributed ‘raft’ protein known as stomatin. The stomatin protein is homologous to the ‘podocin’ protein, the gene for which is mutated in a recessively inherited form of nephrotic syndrome. Among other possible functions, both proteins could be involved in the trafficking of membrane proteins to and from the plasma membrane.
Identification and characterization of human taste receptor genes belonging to the TAS2R family
Authors: Conte C. , Ebeling M. , Marcuz A. , Nef P. , Andres-Barquin P.J.
Published: April 2003

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R/T2R family of taste receptor genes. TAS2R receptors are expressed at the surface of taste receptor cells and are coupled to G proteins and second messenger pathways. We have identified, cloned and characterized 11 new bitter taste receptor genes and four new pseudogenes that belong to the human TAS2R family. Their encoded proteins have between 298 and 333 amino acids and share between 23 and 86% identity with other human TAS2R proteins. Screening of a mono-chromosomal somatic cell hybrid panel to assign the identified bitter taste receptor genes to human chromosomes demonstrated that they are located in chromosomes 7 and 12. Including the 15 sequences identified, the human TAS2R family is composed of 28 full-length genes and 16 pseudogenes. Phylogenetic analyses suggest a classification of the TAS2R genes in five groups that may reflect a specialization in the detection of specific types of bitter chemicals.
Impact of the Human Genome Project on Pediatric Endocrinology
Authors: Polychronakos Constantin
Published: April 2003

A genomic approach to human biology involves examination of the entire complement of human genes and their protein products in contradistinction to the conventional phenomena-driven examination of individual components, one at a time. This approach may have limitations, but it also has the potential to increase our knowledge by an order of magnitude or more. It is expected that it will leave no field of biology and medicine unaffected, and this includes endocrinology. The structural and functional aspects of the human genome are reviewed, and the nature of the novel knowledge from the genome effort (acquired or expected) is described. More importantly, an overview is given of new ways of thinking and new approaches to endocrine research using genomic concepts and tools. Although these research breakthroughs have relatively few applications in clinical practice at the present moment, the clinician must expect drastic changes in diagnostics and therapeutics in the next decade or two, and endocrine- specific examples of such applications are given. Finally, the question is raised of social and ethical issues that these developments are generating.
Violent Women, Blame Attribution, Crime, and Personality
Authors: Weizmann-Henelius G. , Sailas E. , Viemerö V. , Eronen M.
Published: April 2003

Background: The attribution of blame for criminal act has an impact, both on the way the offender must come to terms with the offence and on the risk of recidivism. Blame attribution has been found to be related to the type of crime and personality. Aims: This study examined the relationship of blame attribution and feelings of guilt in violent female offenders, according to factors related to crime, background and personality. Methods: The Gudjonsson Blame Attribution Inventory (BAI) and the Defense Style Questionnaire (DSQ) were administered to 58 violent female offenders. The Hare Psychopathy Checklist-Revised (PCL-R), Structured Clinical Interview II for DSM-IV (SCID II) and clinical interviews were used for assessment. Results: Lower scores of guilt feelings were found in women than has been reported for men. The feelings of guilt were higher in homicide than in other violent crimes, but lower in the cases where women had committed prior violent crimes. No differences were found between psychiatric patients and prisoners. The duration of hospitalisation and incarceration did not result in differences in blame attribution and guilt, but when the victims survived, guilt feelings seemed to increase with the passing of the time. External attribution was related to motives of crime, but traumatic experiences did not have a crucial impact upon blame attribution. The attribution of blame and the amount of guilt feelings were found to be related to personality. Women scoring high on psychopathy reported less guilt than women with low scores. The corresponding result was not obtained in the group of women with antisocial personality disorder, who, however, showed an unexpectedly low use of external attribution. Conclusion: The results suggest that it might be difficult for women to cope with the violent offence and that the characteristics of psychopathy seems to have a crucial impact on the guilt feelings and consequently on coping with the crime in female offenders.
Effects of Galanin-Like Peptide on Food Intake and the Hypothalamo-Pituitary-Thyroid Axis
Authors: Seth Asha , Stanley Sarah , Dhillo Waljit , Murphy Kevin , Ghatei Mohammad , Bloom Stephen
Published: April 2003

Galanin-like peptide (GALP) is a novel hypothalamic peptide synthesised in neurons in the arcuate nucleus which project to the paraventricular nucleus (PVN). GALP has recently been identified as an orexigenic peptide. In this study we aimed to further characterise the hypothalamic action of this peptide in energy homeostasis. Firstly, we investigated the orexigenic effect of GALP in the PVN and compared its effects with galanin and galanin 2–29. Secondly, we examined the effect of PVN administration of GALP and galanin on circulating thyroid-stimulating hormone (TSH). PVN administration of GALP significantly increased the food intake of satiated rats 1 h after administration at doses of 0.3, 1 and 3 nmol. In comparison with paraventricular administration of galanin, GALP was a more potent orexigen, whereas galanin 2–29, the relatively selective GAL R2 agonist, had no effect on food intake. Both GALP and galanin administration (1 nmol) into the PVN significantly decreased the level of circulating TSH. To investigate the mechanism of these effects, we examined the effect of GALP and galanin application on neuropeptide release from hypothalamic explants in vitro. GALP peptide (100 nM) stimulated the release of the orexigenic peptide neuropeptide Y from hypothalamic explants and decreased the release of the anorectic peptide cocaine-and-amphetamine-regulated transcript, whereas galanin (100 nM) peptide had no significant effect on the release of either peptide. Both GALP (100 nM) and galanin (100 nM) inhibited the release thyrotrophin-releasing hormone. These data suggest that in the PVN, GALP may play a role in energy homeostasis by stimulating food intake and suppressing TSH release.
Expression of D1 and D2 Dopamine Receptors in the Hypothalamus and Pituitary during the Turkey Reproductive Cycle: Colocalization with Vasoactive Intestinal Peptide
Authors: Chaiseha Yupaporn , Youngren Orlan , Al-Zailaie Khaled , El Halawani Mohamed
Published: April 2003

The regulation of avian prolactin (PRL) secretion and PRL gene expression is influenced by hypothalamic vasoactive intestinal peptide (VIP), the PRL-releasing factor in avian species. Recent evidence indicates that D1 and D2 dopamine (DA) receptors play a pivotal role in VIP and PRL secretion. The differential expression of DA receptors located on hypothalamic VIP neurons and anterior pituitary cells may affect the degree of prolactinemia observed during the turkey reproductive cycle. The relative expression of D1D and D2 DA receptor subtype mRNA was quantitated using in situ hybridization histochemistry (ISH). D1D and D2 DA receptor mRNA was found expressed throughout the hypothalamus and pituitary. The expression of D1D DA receptor mRNA in the hypothalamus was found to be 6.8-fold greater than that of D2 DA receptor mRNA. Higher D1D DA receptor mRNA content was found in the anterior hypothalamus (3.6-fold), the ventromedial nucleus (2.0-fold), the infundibular nuclear complex (INF; 1.9-fold), and the medial preoptic nucleus (1.5-fold) of laying hens as compared to that of reproductively quiescent non-photostimulated hens. The levels seen in incubating hyperprolactinemic hens were essentially the same as in laying hens, except for the INF where levels were 52% higher. During the photorefractory stage (hypoprolactinemia), the D1D DA receptor mRNA was at its lowest level in all areas tested. No differences were observed in hypothalamic D2 DA receptor mRNA abundance throughout the reproductive cycle, except for an increase in D2 DA receptor mRNA within the INF of photorefractory hens. Also, a marked reduction in D2 DA receptor mRNA was observed in the pituitary of incubating hens. Pituitary D1D DA receptor levels did not change when birds entered the incubating phase. Double ISH revealed that D1D and D2 DA receptor mRNAs were co-expressed within neurons expressing VIP mRNA, predominantly within the lateral hypothalamus and INF. D1D DA receptor mRNA was more highly expressed than D2 DA receptor mRNA. The present findings clearly demonstrate that the expression of stimulatory D1 DA receptor mRNA in the hypothalamus increases in hyperprolactinemic incubating hens, whereas inhibitory D2 DA receptor mRNA increases in the pituitary of hypoprolactinemic photorefractory hens.
Escherichia coli Response to Exogenous Pyrophosphate and Analogs
Authors: Biville Francis , Oshima Taku , Mori Hirotada , Kawagoe Yuya , Bouvet Odile , Rager Marie-Noëlle , Perrotte-Piquemal Marina , Danchin Antoine
Published: April 2003

The addition of exogenous pyrophosphate increases the growth yield and cAMP synthesis in stationary phase when Escherichia coli is grown in minimal medium. Pyrophosphate increases the yield by altering the enterobactin uptake system. We studied the physiological effects and examined how the E. coli transcriptome was modified when two structural analogs of pyrophosphate were added to the growth medium. Methylenediphosphonic acid or a high concentration of iron had the same positive effects as pyrophosphate on growth yield, cAMP synthesis and the repression of Fur-regulated genes. In contrast, imidodiphosphate did not affect these cellular processes significantly. The transcriptome modifications generated by pyrophosphate or methylenediphosphonic acid were more similar than those generated by imidodiphosphate or excess iron. The transcriptome data also indicated that processes other than iron uptake might be involved in the cellular response to exogenous pyrophosphate or methylenediphosphonic acid.
Elevated Suicide Risk among Patients with Multiple Sclerosis in Sweden
Authors: Fredrikson S. , Cheng Q. , Jiang G.-X. , Wasserman D.
Published: April 2003

Results from previous studies of suicide risk among patients with multiple sclerosis (MS) are inconsistent. This may be explained partly by differences in methodology and study populations. The purpose of our study was to investigate suicide risk among hospital patients with MS in Sweden. During the period 1969–1996, 12,834 cases were recorded in the Swedish Hospital Inpatient Register, with 77,377 hospital admissions, in which MS was a primary or secondary diagnosis at discharge. The mean follow-up time for the whole cohort was 9.9 (SD 7.3) years. When the data for these MS patients were linked to the Swedish Causes of Death Register for the same period, 5,052 (39.4%) were found to have died. Among the 5,052 deaths, suicide was an underlying cause of death in 90 cases (1.8%). The mean period between the initial admission date with an MS diagnosis at discharge and the date of death for the 90 MS suicide cases was 5.8 (SD 5.1) years. This was significantly shorter (p = 0.002) than the mean of 7.9 (SD 6.4) years for MS cases who died due to other causes. Suicide risk, calculated as the standardized mortality ratio (SMR), was significantly elevated (SMR = 2.3) among both male and female MS cases compared with the general population. Suicide risk was particularly high in the first year after initial admission with an MS diagnosis, and among younger male MS cases. The mean age at the time of suicide was 44.5 (SD 12.4) years, and 58% of the suicides were committed within 5 years after the first admission with an MS diagnosis. The crude suicide rate among MS patients during the study period was 71 per 100,000 person-years. The rate was significantly higher (p < 0.001) in males (114) than in females (47), with an odds ratio of 2.4 (95% CI: 1.6–3.8). These findings have implications for suicide preventive measures in neurological practice.