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1.
J Genet Couns ; 30(5): 1285-1291, 2021 10.
Article in English | MEDLINE | ID: mdl-34558759

ABSTRACT

The COVID-19 pandemic poses a significant challenge to healthcare professionals and health systems around the world, most notably the disruption of its service delivery. The typical work setting for most genetic counselors (GCs) is in a clinic or hospital. However, during the COVID-19 pandemic, to help prevent the further spread of the virus, clinics and hospitals have restricted non-urgent in-person delivery of healthcare services, including genetic counseling. Patients' access to genetic counseling services has thus been limited, which prompted GCs in the country to utilize an alternative way to provide counseling through telegenetics. With the expansion of genetic services in the country, including the full implementation of expanded newborn screening, there is an increasing demand for genetic counseling and a growing need for telegenetics.


Subject(s)
COVID-19 , Telemedicine , Genetic Counseling , Humans , Infant, Newborn , Pandemics , Philippines , SARS-CoV-2
2.
Acta Medica Philippina ; : 394-399, 2020.
Article in English | WPRIM (Western Pacific) | ID: wpr-979898

ABSTRACT

Introduction@#Midwives play an important role in promoting newborn screening (NBS) and they ensure that all Filipino newborns are offered screening for life-threatening metabolic conditions. Of the disorders included in NBS, Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency is the most common disorder detected. @*Objectives@#This study aimed to assess the knowledge, self-perceived role, and experience of midwives who practice in urban and rural settings in educating parents of a newborn who are confirmed cases for G6PD deficiency. @*Method@#One-on-one semi structured interview was conducted among 21 midwives from Manila City and Lipa, Batangas, Philippines. @*Results@#The study findings indicate that midwives frequently serve as the primary information resource for parents of infants with G6PD deficiency. Assessment of knowledge showed that midwives have sufficient knowledge about the medical management and the necessary follow-up of infants with G6PD deficiency. However, it also revealed that they have inadequate knowledge of the underlying genetic cause of G6PD deficiency. The surveyed midwives recognized their role and the importance of proper education regarding G6PD deficiency. @*Conclusion@#The findings of this study identified gaps in the midwives’ knowledge on the genetic mechanisms and inheritance of G6PD deficiency, which could be a basis to improve the education and dissemination of information and to eventually improve parental education and care of newborns with G6PD deficiency


Subject(s)
Genetic Counseling , Glucosephosphate Dehydrogenase Deficiency , Neonatal Screening
3.
Int J Mol Imaging ; 2011: 828151, 2011.
Article in English | MEDLINE | ID: mdl-21603241

ABSTRACT

Aim. To develop a method and obtain proof-of-principle for immunolymphoscintigraphy for identification of metastatic sentinel nodes. Methods. We selected one of four tumour-specific antibodies against human breast cancer and investigated (1), in immune-deficient (nude) mice with xenograft human breast cancer expressing the antigen if specific binding of the intratumorally injected, radioactively labelled, monoclonal antibody could be scintigraphically visualized, and (2) transportation to and retention in regional lymph nodes of the radioactively labelled antibody after subcutaneous injection in healthy rabbits. Results and Conclusion. Our paper suggests the theoretical possibility of a model of dual isotope immuno-lymphoscintigraphy for noninvasive, preoperative, malignant sentinel node imaging.

4.
Diabetes Obes Metab ; 11(8): 795-803, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19519868

ABSTRACT

AIM/HYPOTHESIS: Combination therapies are increasingly common in the clinical management of type 2 diabetes. We investigated to what extent combined treatment with the human glucagon-like peptide-1 (GLP-1) analogue liraglutide and the dual PPARalpha/gamma agonist ragaglitazar would improve glycaemic control in overtly diabetic Zucker diabetic fatty (ZDF) rats. METHODS: Ninety overtly diabetic male ZDF rats were stratified into groups with matched haemoglobin A1c (HbA1c) (9.0+/-0.1%). Liraglutide (15 and 50 microg/kg subcutaneously twice daily), ragaglitazar (1 and 3 mg/kg perorally once daily) and their vehicles were studied as monotherapy and in combination in a 3x3 factorial design. RESULTS: After 4-week treatment, synergistic effects on HbA1c, non-fasting morning blood glucose (BG) and/or 24-h BG profiles were observed with three of the four combinations. The relationship between plasma insulin and BG in combination-treated animals approached that of historical lean ZDF rats representing normal glucose homeostasis, suggesting that insulin secretion and insulin sensitivity were markedly improved. Increased insulin immunostaining in islets further supports the improved beta-cell function and/or insulin sensitivity in combination-treated animals. The synergistic effect on glycaemic control was found without a similar synergistic increase in beta-cell mass in the combination groups. CONCLUSIONS/INTERPRETATION: Our data demonstrate that combination treatment with a human GLP-1 analogue and a dual PPARalpha/gamma agonist through distinct mechanism of actions synergistically improves glycaemic control in the ZDF rat.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus/drug therapy , Glucagon-Like Peptide 1/analogs & derivatives , Hypoglycemic Agents/pharmacology , Oxazines/therapeutic use , Phenylpropionates/therapeutic use , Animals , Cell Proliferation/drug effects , Disease Models, Animal , Drug Synergism , Glucagon-Like Peptide 1/therapeutic use , Glycated Hemoglobin/analysis , Homeodomain Proteins/analysis , Homeostasis/drug effects , Immunohistochemistry , Insulin/blood , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/immunology , Liraglutide , Rats , Rats, Zucker , Trans-Activators/analysis
5.
Br J Dermatol ; 160(2): 284-96, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18945296

ABSTRACT

BACKGROUND: Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. OBJECTIVES: In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. METHODS: We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. RESULTS: We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. CONCLUSIONS: The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment.


Subject(s)
Interleukins/physiology , Psoriasis/etiology , Signal Transduction/immunology , Skin Transplantation , Adult , Aged , Animals , Antibody Specificity/immunology , Cell Proliferation , Humans , Interleukins/antagonists & inhibitors , Interleukins/immunology , Mice , Mice, SCID , Middle Aged , Psoriasis/drug therapy , Psoriasis/immunology , Recombinant Proteins/immunology , Remission Induction , Transplantation, Heterologous
6.
Microvasc Res ; 75(2): 169-78, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17976661

ABSTRACT

The matrix-inserted surface transplantation model is an in vivo assay used to analyse the kinetics of tumor-vessel interactions during different stages of skin carcinoma progression. This system allows the study of host-tumor interface, i.e. penetration of tumor cells into normal host tissue as well as infiltration of normal host cells into the tumor. In the present study, image analysis algorithms for processing and quantifying the extent of such migratory and tissue remodeling events are presented. The proposed method is non-parametric and its originality lies in its particularity to take into account the specific geometry of tumor-host interface. This methodology is validated by evaluating the contribution of matrix metalloproteases (MMPs) in skin carcinoma invasion and vascularization through pharmacological and genetic approaches.


Subject(s)
Neovascularization, Pathologic/pathology , Signal Processing, Computer-Assisted , Skin Neoplasms/blood supply , Skin Neoplasms/pathology , Algorithms , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Animals , Cell Line, Tumor , Cell Movement , Dipeptides/pharmacology , Dipeptides/therapeutic use , Kinetics , Matrix Metalloproteinases, Secreted/antagonists & inhibitors , Matrix Metalloproteinases, Secreted/genetics , Matrix Metalloproteinases, Secreted/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Statistical , Neoplasm Invasiveness , Neovascularization, Pathologic/enzymology , Neovascularization, Pathologic/prevention & control , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , Reproducibility of Results , Skin Neoplasms/enzymology , Skin Neoplasms/prevention & control , Stromal Cells/pathology
7.
J Thromb Haemost ; 5(9): 1936-44, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17723133

ABSTRACT

BACKGROUND: Degradation of extracellular matrix proteins, such as fibrin, is pivotal to tumor invasion. Inhibition of the interaction between urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and hence pro-u-PA activation, is an attractive approach to anti-invasive cancer therapy. A number of inhibitors exist for the human system, but because of species specificity none of these are efficient in mice. We have recently generated an inhibitory monoclonal antibody (mAb) against mouse u-PAR (mR1) by immunization of u-PAR-deficient mice. OBJECTIVES: To evaluate the effect of mR1 in vivo in a physiological setting sensitive to deregulated fibrinolysis, we have administered mR1 systemically and quantitated the effect on liver fibrin accumulation. METHODS: Wild-type and tissue-type plasminogen activator (t-PA) deficient mice were administered with mR1, or control antibody, during 6 weeks. Thereafter, the livers were retrieved and the amount of liver fibrin measured by unbiased morphometrical analysis of immunofluorescence signal. RESULTS: Systemic administration of mR1 caused significantly increased fibrin signal in anti-u-PAR treated t-PA-deficient mice compared to mock-treated, which mimics the phenotype of u-PAR;t-PA double-deficient mice. Fibrin and fibronectin accumulated within the sinusoidal space and was infiltrated by inflammatory cells. Analysis of small and rare hepatic fibrin plaques observed in t-PA-deficient mice showed infiltrating macrophages that, contrary to surrounding Kuppfer cells, expressed u-PAR. CONCLUSION: We show that u-PAR-expressing macrophages are involved in cell-mediated fibrinolysis of liver fibrin deposits, and that the antimouse-u-PAR mAb is effective in vivo and thus suited for studies of the effect of targeting the u-PA/u-PAR interaction in mouse cancer models.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Fibrin/metabolism , Liver/drug effects , Receptors, Cell Surface/immunology , Tissue Plasminogen Activator/genetics , Animals , Antibodies, Monoclonal/pharmacology , Fluorescent Antibody Technique , Liver/metabolism , Mice , Mice, Inbred C57BL , Receptors, Urokinase Plasminogen Activator
8.
J Mol Endocrinol ; 35(2): 231-43, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16216905

ABSTRACT

Growth hormone and prolactin are important growth factors for pancreatic beta-cells. The effects exerted by these hormones on proliferation and on insulin synthesis and secretion in beta-cells are largely mediated through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Suppressors of cytokine signaling (SOCS) proteins are specific inhibitors of the JAK/STAT pathway acting through a negative-feedback loop. To investigate in vivo effects of SOCS-3 in growth hormone (GH)/prolactin signaling in beta-cells we generated transgenic mice with beta-cell-specific overexpression of SOCS-3. The relative beta-cell proliferation and volume in the mice were measured by morphometry. Beta-cell volume of transgenic female mice was reduced by over 30% compared with beta-cell volume in wild-type female mice. Stimulation of transgenic islets in vitro with GH showed a reduced tyrosine phosphorylation of STAT-5 when compared with wild-type islets. Transduction of primary islet cultures with adenoviruses expressing various SOCS proteins followed by stimulation with GH or glucagon-like peptide-1 (GLP-1) revealed that SOCS-3 inhibited GH- but not GLP-1-mediated islet cell proliferation, indicating that the decreased beta-cell volume observed in female transgenic mice could be caused by an inhibition of GH-induced beta-cell proliferation by SOCS-3. In spite of the reduced beta-cell volume the transgenic female mice exhibited enhanced glucose tolerance compared with wild-type littermates following an oral glucose-tolerance test. Together these data suggest that SOCS-3 modulates cytokine signaling in pancreatic beta-cells and therefore potentially could be a candidate target for development of new treatment strategies for diabetes.


Subject(s)
Cell Proliferation , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/physiology , Suppressor of Cytokine Signaling Proteins/metabolism , Animals , Blood Glucose/metabolism , Body Weight , Female , Glucagon-Like Peptide 1/metabolism , Glucose Tolerance Test , Growth Hormone/metabolism , In Situ Hybridization , Insulin/metabolism , Janus Kinase 1 , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Transgenic , Protein-Tyrosine Kinases/metabolism , Random Allocation , Rats , STAT5 Transcription Factor/metabolism , Signal Transduction/physiology , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins/genetics , Transgenes
9.
Clin Exp Immunol ; 141(3): 549-57, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16045746

ABSTRACT

Summary CD4(+)CD25(+) regulatory T cells (T(regs)) are involved in the maintenance of peripheral tolerance and ensure a balanced immune response competent of fighting pathogens and at the same time recognizing commensals as harmless. This feature is lost in Crohn's disease (CD). The forkhead/winged helix transcription factor FoxP3 is a master gene for T(reg) function and defects in the FoxP3 gene lead to a clinical picture similar to inflammatory bowel disease (IBD). Murine colitis can be cured by adoptive transfer of T(regs) and ex vivo-generated gut-specific T(regs) represent an attractive option for therapy in CD. Thus, defective T(regs) could contribute to the development of CD. We cultured biopsies of colonic mucosa in the presence of high concentrations of interleukin (IL)-2 and IL-4 to overcome the anergic nature of naturally occurring CD4(+)CD25(+) T(regs) in the mucosa. We investigated the expression of FoxP3 and regulatory potential of gut-derived CD4(+)CD25(+) T cells cultured from patients with CD and healthy individuals. The FoxP3 expression was analysed by reverse transcriptase polymerase chain reaction (RT-PCR), and the suppressive effect of FoxP3(+)CD4(+)CD25(+) T cells on proliferation and cytokine production of autologous CD4(+) T cells was assessed by flow cytometry. Cultured gut-derived T cells with CD4(+)CD25(+) phenotype expressed FoxP3 and were able as the freshly isolated T(regs) from peripheral blood to suppress proliferation and cytokine production of autologous CD4(+) T cells. Thus, we demonstrate that FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be propagated in vitro from inflamed mucosa of CD patients, which may be of interest in adoptive immunotherapy.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Colon , Crohn Disease/immunology , DNA-Binding Proteins/analysis , Intestinal Mucosa/immunology , Receptors, Interleukin-2/analysis , Adult , CD4-Positive T-Lymphocytes/metabolism , Case-Control Studies , Cells, Cultured , DNA-Binding Proteins/genetics , Down-Regulation , Female , Flow Cytometry , Forkhead Transcription Factors , Humans , Interferon-gamma/immunology , Interleukin-2/immunology , Interleukin-4/immunology , Male , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/immunology
10.
Article in German | MEDLINE | ID: mdl-15605297

ABSTRACT

We report on a 36 year old patient who collapsed at home and was resuscitated by prehospital medical emergency services. He presented on scene unconscious with severe ST-elevations on the ECG and hardly palpable pulses. His previous medical history included only idiopathic hypertension and his professional background as manager of a company was associated with high stress levels. The prehospital diagnosis was myocardial infarction with cardiogenic shock. A hypovolemic shock was excluded from the differential diagnosis because of the age of the patient, lack of a precipitating trauma and inconsistent symptoms. The patient died after terminating prolonged resuscitation. A post mortem showed as cause of death the rupture of a splenic artery aneurysm. We emphasize that a cardiovascular collapse in a young patient without specific history or trauma still can be caused by hypovolemic shock due to intra-abdominal or -thorac bleeding.


Subject(s)
Aneurysm, Ruptured/diagnosis , Spleen/blood supply , Splenic Diseases/diagnosis , Adult , Diagnosis, Differential , Emergencies , Fatal Outcome , Female , Humans , Resuscitation
11.
Clin Exp Immunol ; 138(1): 66-74, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15373907

ABSTRACT

Integrin alpha4beta 7 is the principal gut-homing receptor, and it is assumed that expression of this specific integrin directs lymphocytes to the gut in vivo. Adoptive cellular immunotherapy against inflammatory bowel disease (IBD) may depend on the expression of integrin alpha4beta 7 to accomplish local delivery of intravenously injected regulatory T cells in inflamed gut mucosa. The present study aimed to investigate whether in vitro expanded human T cells from the colonic mucosa maintain integrin expression, show in vitro adhesion and retain in vivo gut-homing properties during cultivation. Whole colonic biopsies from healthy subjects were cultured in the presence of interleukin-2 (IL-2) and IL-4. The integrin expression of the cultured T cells was determined by flow cytometry and in vitro adhesion was assessed in a mucosal addressin cell adhesion molecule 1 (MAdCAM-1) adhesion assay. We studied the homing pattern after autologous infusion of 3 x 10(8 111)Indium ((111)In)-labelled T cells in five healthy subjects using scintigraphic imaging. The cultured CD4(+)CD45RO(+) gut-derived T cells express higher levels of integrin alpha4beta 7 than peripheral blood lymphocytes (PBLs) and show strong adhesion to MAdCAM-1 in vitro, even after (111)In-labelling. Scintigraphic imaging, however, showed no gut-homing in vivo. After prolonged transit through the lungs, the T cells migrated preferentially to the spleen, liver and bone marrow. In conclusion, it is feasible to infuse autologous T cells cultured from the gut mucosa, which may be of interest in adoptive immunotherapy. Despite high expression of the gut-homing integrin alpha4beta 7 and adhesion to MAdCAM-1 in vitro, evaluation by (111)In-scintigraphy demonstrated no gut-homing in healthy individuals.


Subject(s)
Colon/immunology , Immunoglobulins/immunology , Integrins/analysis , Intestinal Mucosa/immunology , Mucoproteins/immunology , T-Lymphocytes/immunology , Adult , Antigens, CD/immunology , Bone Marrow/immunology , Cell Adhesion/immunology , Cell Adhesion Molecules , Cell Movement/immunology , Cells, Cultured , Female , Humans , Indium Radioisotopes , Integrins/immunology , Interleukin-2/immunology , Interleukin-4/immunology , Liver/immunology , Lung/immunology , Male , Middle Aged , Receptors, Lymphocyte Homing/immunology , Spleen/immunology
12.
Eur J Endocrinol ; 150(6): 893-904, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15191361

ABSTRACT

OBJECTIVE: The aim was to investigate the possible interactions of the two peripheral hormones, leptin and ghrelin, that regulate the energy balance in opposite directions. METHODS: Leptin-receptor mutated Zucker diabetic fatty (ZDF) and lean control rats were treated with the ghrelin-receptor ligand, tabimorelin (50 mg/kg p.o.) for 18 days, and the effects on body weight, food intake and body composition were investigated. The level of expression of anabolic and catabolic neuropeptides and their receptors in the hypothalamic area were analysed by in situ hybridization. RESULTS: Tabimorelin treatment induced hyperphagia and adiposity (increased total fat mass and gain in body weight) in lean control rats, while these parameters were not increased in ZDF rats. Treatment with tabimorelin of lean control rats increased hypothalamic mRNA expression of the anabolic neuropeptide Y (NPY) mRNA and decreased hypothalamic expression of the catabolic peptide pro-opiomelanocortin (POMC) mRNA. In ZDF rats, the expression of POMC mRNA was not affected by treatment with tabimorelin, whereas NPY mRNA expression was increased in the hypothalamic arcuate nucleus. CONCLUSION: This shows that tabimorelin-induced adiposity and hyperphagia in lean control rats are correlated with increased hypothalamic NPY mRNA and decreased POMC mRNA expression. The elimination of tabimorelin-induced adiposity and hyperphagia in ZDF rats may be due to lack of POMC mRNA downregulation. In conclusion, we suggest that ghrelin-receptor ligands exert their adipogenic and orexigenic effects via hypothalamic mechanisms that are dependent on intact leptin-receptor signalling.


Subject(s)
Body Composition/drug effects , Dipeptides/pharmacology , Eating/drug effects , Receptors, Cell Surface/physiology , Receptors, G-Protein-Coupled/physiology , Signal Transduction , Adipose Tissue/drug effects , Animals , Body Weight/drug effects , Gene Expression , Hyperphagia/chemically induced , Hypothalamus/chemistry , In Situ Hybridization , Mutation , Neuropeptide Y/genetics , Pro-Opiomelanocortin/genetics , RNA, Messenger/analysis , Rats , Rats, Zucker , Receptors, Cell Surface/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, Ghrelin , Receptors, Leptin
13.
J Contam Hydrol ; 61(1-4): 219-33, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12598106

ABSTRACT

Within the scope of a bilateral cooperation between Svensk Kärnbränslehantering (SKB) and Forschungszentrum Karlsruhe, Institut für Nukleare Entsorgung (FZK-INE), an actinide migration experiment is currently being performed at the Aspö Hard Rock Laboratory (HRL) in Sweden. This paper covers laboratory and in situ investigations on actinide migration in single-fractured granite core samples. For the in situ experiment, the CHEMLAB 2 probe developed by SKB was used. The experimental setup as well as the breakthrough of inert tracers and of the actinides Am, Np and Pu are presented. The breakthrough curves of inert tracers were analyzed to determine hydraulic properties of the fractured samples. Postmortem analyses of the solid samples were performed to characterize the flow path and the sorbed actinides. After cutting the cores, the abraded material was analyzed with respect to sorbed actinides. The slices were scanned optically to visualize the flow path. Effective volumes and inner surface areas were measured. In the experiments, only breakthrough of Np(V) was observed. In each experiment, the recovery of Np(V) was < or = 40%. Breakthrough of Am(III) and Pu(IV) as well as of Np(IV) was not observed.


Subject(s)
Actinoid Series Elements/analysis , Silicon Dioxide/chemistry , Geological Phenomena , Geology , Germany , International Cooperation , Radioactive Waste , Sweden
14.
Proc Natl Acad Sci U S A ; 100(3): 1438-43, 2003 Feb 04.
Article in English | MEDLINE | ID: mdl-12552113

ABSTRACT

Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic alpha cells in response to low blood glucose. To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor (Gcgr(-/-)). These mice display lower blood glucose levels throughout the day and improved glucose tolerance but similar insulin levels compared with control animals. Gcgr(-/-) mice displayed supraphysiological glucagon levels associated with postnatal enlargement of the pancreas and hyperplasia of islets due predominantly to alpha cell, and to a lesser extent, delta cell proliferation. In addition, increased proglucagon expression and processing resulted in increased pancreatic glucogen-like peptide 1 (GLP-1) (1-37) and GLP-1 amide (1-36 amide) content and a 3- to 10-fold increase in circulating GLP-1 amide. Gcgr(-/-) mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure. These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and alpha and delta cell numbers. Furthermore, the lean phenotype of Gcgr(-/-) mice suggests glucagon action may be involved in the regulation of whole body composition.


Subject(s)
Blood Glucose/metabolism , Glucagon/blood , Islets of Langerhans/pathology , Receptors, Glucagon/genetics , Receptors, Glucagon/physiology , Animals , Body Weight , Calorimetry , Cell Division , Cyclic AMP/metabolism , Epididymis/metabolism , Epinephrine/pharmacology , Glucose/metabolism , Hormones/metabolism , Hyperplasia , Immunohistochemistry , Insulin/metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence , Phenotype , Time Factors
15.
Appl Radiat Isot ; 57(5): 687-95, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12433043

ABSTRACT

Based on a high affinity to the enzyme estrone sulfatase (ES), 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate ([18F]FESDS) has been suggested as a potential PET radiotracer for imaging steroid-dependent breast tumours. The distribution of [18F]FESDS was studied in rats, tumour-bearing nude mice and piglets. In all species evidence for binding to a second target, the enzyme carbonic anhydrase (CA), was obtained. ES and CA inhibitors significantly reduced the radiotracer uptake in various organs but not in tumours. It is concluded that [18F]FESDS binds to ES and CA in vivo but this binding is not strong enough to allow tumour imaging with positron emission tomography (PET).


Subject(s)
Estradiol/analogs & derivatives , Fluorine Radioisotopes , Neoplasms, Experimental/diagnostic imaging , Radiopharmaceuticals , Animals , Breast Neoplasms/diagnostic imaging , Estradiol/chemical synthesis , Estradiol/pharmacokinetics , Female , Fluorine Radioisotopes/pharmacokinetics , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Wistar , Swine , Tissue Distribution , Tomography, Emission-Computed , Transplantation, Heterologous , Tumor Cells, Cultured
16.
Environ Sci Technol ; 36(21): 4483-8, 2002 Nov 01.
Article in English | MEDLINE | ID: mdl-12433155

ABSTRACT

Groundwater colloids from the Gorleben site (Lower Saxony, Germany) are characterized in the presence of Eu(III) by tapping-mode atomic force microscopy (AFM) with phase contrast imaging. Using a liquid cell the method allows investigations of samples being in contact with aqueous solution. This ensures that complex structures are kept in their native hydrated state. Different types of colloids and aggregates are found by AFM, e.g., spherical particles, fibrous structures, and structures which appear to be hollow. A partial coating of the edges of clay particles with humic colloids can be assumed from phase contrast images. Therefore, aquatic colloids and their aggregates found in Gorleben groundwater can be characterized as a complex mixture of components, which may influence the migration of groundwater contaminants in different processes.


Subject(s)
Colloids/analysis , Environmental Monitoring/methods , Soil Pollutants/analysis , Water Pollutants/analysis , Germany , Humic Substances/analysis , Microscopy, Atomic Force
17.
Appl Radiat Isot ; 56(6): 773-80, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12102332

ABSTRACT

16Alpha-fluoroestradiol-3,17beta-disulfamate (FESDS) strongly inhibits estrone sulfatase (ES), an enzyme which is also present in the brain. The enzyme is probably involved in important regulatory functions of neurosteroids which may be disturbed in certain brain diseases. In the present study, [18F]FESDS was used to measure the amount of ES in various rat brain regions using quantitative in vitro autoradiography. The obtained values vary between 0.29 pmol (mg protein)(-1) (pons) and 11.5 pmol (mg protein)(-1) (striatum). They are positively correlated with the enzyme activity measured in homogenates of the corresponding regions. Because this radiotracer binds also to carbonic anhydrase in the brain it is only of limited use for in vivo imaging studies.


Subject(s)
Brain/enzymology , Estradiol/pharmacokinetics , Fluorine Radioisotopes , Sulfatases/metabolism , Adenocarcinoma , Animals , Autoradiography/methods , Breast Neoplasms , Estradiol/analogs & derivatives , Female , Humans , Kinetics , Organ Specificity , Rats , Reverse Transcriptase Polymerase Chain Reaction , Sulfatases/genetics , Transcription, Genetic , Tumor Cells, Cultured
18.
Appl Radiat Isot ; 55(5): 631-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11573796

ABSTRACT

After 16alpha-[15F]fluoroestradiol ([18F]FES) has been successfully prepared in an automated module, the synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate ([18F]FESDS) is described as a module-assisted one-pot procedure which can provide 10GBq [18F]FESDS with a radiochemical purity better than 99%. The procedure is reliable and reproducible and requires a time of about 90 min. Because of its high sulphatase-inhibitory effect [15F]FESDS is thought to be a new PET tracer to image sites of high sulphatase activity.


Subject(s)
Estradiol/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Arylsulfatases/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Estradiol/analogs & derivatives , Fluorine Radioisotopes , Humans , Radiochemistry/instrumentation , Radiochemistry/methods , Steryl-Sulfatase , Tomography, Emission-Computed
19.
Endocrine ; 14(1): 63-6, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11322502

ABSTRACT

The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.


Subject(s)
Bone Remodeling/drug effects , Growth Hormone-Releasing Hormone/pharmacology , Growth Hormone/pharmacology , Hormones/pharmacology , Peptide Hormones , Adult , Age Factors , Animals , Bone Development/drug effects , Bone Resorption/physiopathology , Bone and Bones/anatomy & histology , Bone and Bones/drug effects , Ghrelin , Growth Hormone/deficiency , Humans , Indoles/pharmacology , Oligopeptides/pharmacology , Organ Size , Peptides/pharmacology , Spiro Compounds/pharmacology
20.
J Leukoc Biol ; 69(3): 397-404, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11261786

ABSTRACT

Organisms belonging to the Mycobacterium avium complex (MAC) cause life-threatening bacteremia in immunocompromised patients. Monocytes and macrophages are thought to be responsible for ingestion and killing of MAC. However, it has been suggested that neutrophils may play a role in the early immune response to MAC infection. Here, neutrophils in autologous plasma were incubated (at 0 and 37 degrees C) with M. avium labeled with Auramine O, a potent fluorochrome. Neutrophil phagocytosis was measured by flow cytometry. Neutrophils incubated at 37 degrees C showed an increase in fluorescence over time with a maximum at 15 min, whereas neutrophils on ice showed no time-dependent increase in FL1. At 15 min Fl 1 at 37 degrees C was twice as high as FL1 at 0 degrees C. Examination under the fluorescent microscope showed multiple intracellular fluorescent mycobacteria. Results in nine independent experiments showed time-dependent decrease of colony-forming units in neutrophil-associated live M. avium. Significant killing was observed within 30 min and was complete by 120 min. Observation by electron microscopy clearly confirmed the presence of intraphagosomal MAC, both intact and with evidence of degradation. These data demonstrate that MAC is rapidly phagocytized and killed by human neutrophils. The newly established flow cytometry method should be useful in further studies of neutrophil function and of the role of G-CSF and other cytokines in MAC disease.


Subject(s)
Mycobacterium avium Complex/immunology , Neutrophils/immunology , Phagocytosis/immunology , Adult , Benzophenoneidum , Blood Sedimentation , Coloring Agents , Cytotoxicity, Immunologic , Female , Flow Cytometry , Humans , Male , Microscopy, Electron , Microscopy, Fluorescence
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