ABSTRACT
True hermaphroditism is a rare intersex disorder in which individuals possess both testicular and ovarian gonadal tissue. A case of true unilateral hermaphroditism presenting with ambiguous external genitalia, right scrotal testis and left pelvic ovotestis is herein outlined Phallic, gonadal and genetic factors were considered before male gender was assigned. Gender assignment procedures have been questioned by intersex activists opposed to early genital surgery. Western societies have a binary perspective on gender and this leads to a stigma being placed on intersex cases. A multidisciplinary approach to this problem involving paediatric specialists in the field, of endocrinology, surgery and psychiatry is necessary, along with educational programmes that promote tolerance in society to variations in gender.
Subject(s)
Humans , Male , Female , Disorders of Sex Development/diagnosis , Gender Identity , Identification, Psychological , Genitalia, Female/anatomy & histology , Genitalia, Male/anatomy & histology , Disorders of Sex Development/genetics , Disorders of Sex Development/pathology , Infant, NewbornABSTRACT
True hermaphroditism is a rare intersex disorder in which individuals possess both testicular and ovarian gonadal tissue. A case of true unilateral hermaphroditism presenting with ambiguous external genitalia, right scrotal testis and left pelvic ovotestis is herein outlined Phallic, gonadal and genetic factors were considered before male gender was assigned. Gender assignment procedures have been questioned by intersex activists opposed to early genital surgery. Western societies have a binary perspective on gender and this leads to a stigma being placed on intersex cases. A multidisciplinary approach to this problem involving paediatric specialists in the field, of endocrinology, surgery and psychiatry is necessary, along with educational programmes that promote tolerance in society to variations in gender.
Subject(s)
Disorders of Sex Development/diagnosis , Gender Identity , Identification, Psychological , Disorders of Sex Development/genetics , Disorders of Sex Development/pathology , Female , Genitalia, Female/anatomy & histology , Genitalia, Male/anatomy & histology , Humans , Infant, Newborn , MaleABSTRACT
Nevirapine is one of the first line antiretroviral agents used in the treatment of HIV/AIDS as well as for prophylaxis against mother-to-child transmission of HIV As antiretroviral medication becomes more available it is important for physicians to recognize the major clinical toxicities of these medications. We report a HIV-infected infant who developed a rash with systemic symptoms in association with nevirapine administration
Subject(s)
Humans , Male , Infant , Anti-HIV Agents/adverse effects , Exanthema/chemically induced , HIV Infections/drug therapy , Nevirapine/adverse effects , Exanthema/physiopathology , Jamaica , Acquired Immunodeficiency Syndrome/drug therapyABSTRACT
Nevirapine is one of the first line antiretroviral agents used in the treatment of HIV/AIDS as well as for prophylaxis against mother-to-child transmission of HIV As antiretroviral medication becomes more available it is important for physicians to recognize the major clinical toxicities of these medications. We report a HIV-infected infant who developed a rash with systemic symptoms in association with nevirapine administration.
Subject(s)
Anti-HIV Agents/adverse effects , Exanthema/chemically induced , HIV Infections/drug therapy , Nevirapine/adverse effects , Acquired Immunodeficiency Syndrome/drug therapy , Exanthema/physiopathology , Humans , Infant , Jamaica , MaleABSTRACT
These case reports describe the clinical course of eight children who were admitted to the University Hospital of the West Indies, Kingston, Jamaica, between July 2000 and November 2001 because of a diagnosis of tuberculosis. This represented an increase in the incidence of the disease in children at this institution. The purpose of this report is to make healthcare workers aware of the resurgence of tuberculosis. The diagnosis of paediatric tuberculosis is challenging and requires a high index of suspicion in the presence of suggestive clinical and laboratory findings. The diagnosis should not be limited to the immunocompromised patient, as in this report the majority of the patients were HIV negative.
Subject(s)
Tuberculosis/epidemiology , Antitubercular Agents/therapeutic use , Child , Child, Preschool , Female , HIV Infections/complications , Hospitals, University , Humans , Incidence , Infant , Male , Tuberculosis/diagnosis , Tuberculosis/drug therapy , West Indies/epidemiologyABSTRACT
These case reports describe the clinical course of eight children who were admitted to the University Hospital of the West Indies, Kingston, Jamaica, between July 2000 and November 2001 because of a diagnosis of tuberculosis. This represented an increase in the incidence of the disease in children at this institution. The purpose of this report is to make healthcare workers aware of the resurgence of tuberculosis. The diagnosis of paediatric tuberculosis is challenging and requires a high index of suspicion in the presence of suggestive clinical and laboratory findings. The diagnosis should not be limited to the immunocompromised patient, as in this report the majority of the patients were HIV negative
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Tuberculosis/epidemiology , Antitubercular Agents/therapeutic use , Hospitals, University , Incidence , HIV Infections/complications , Tuberculosis/diagnosis , Tuberculosis/drug therapy , West Indies/epidemiologyABSTRACT
Rapid massive breast hypertrophy occasionally occurs at the time of puberty or during pregnancy, with breast size eventually becoming burdensome or incapacitating to the patient. Pregnancy-related breast hypertrophy is often arrested or reversed by reducing serum prolactin levels with bromocriptine therapy. Unfortunately, breast enlargement in our 12-year-old patient with massive juvenile mammary hypertrophy was unaffected by bromocriptine therapy despite a reduction of her prolactin to normal levels. Two reduction mammaplasties followed by subcutaneous mastectomy were required to control breast hypertrophy. Breast-tissue hypersensitivity to prolactin appears to be a characteristic of pregnancy-related gigantomastia. Our pubertal patient with juvenile mammary hypertrophy failed to respond to bromocriptine therapy, so the aetiology of this syndrome may involve breast-tissue hypersensitivity to hormones other than prolactin.
Subject(s)
Breast/pathology , Bromocriptine/therapeutic use , Hormone Antagonists/therapeutic use , Prolactin/antagonists & inhibitors , Child , Female , Humans , Hyperprolactinemia/complications , Hypertrophy/drug therapy , Hypertrophy/surgery , Mammaplasty/methods , Mastectomy, Subcutaneous , Treatment FailureABSTRACT
Near-haploid (<30 chromosomes) acute lymphoblastic leukemia (ALL) is a rare and unique subgroup of childhood common ALL associated with a very poor outcome. It may be underdiagnosed when masked by a co-existing hyperdiploid line, which has to be distinguished from the common good-prognostic hyperdiploid (>50 chromosomes) ALL. We present three children in whom, by conventional cytogenetics, near-haploid ALL was detected on relapse. Using interphase FISH probes of chromosomes X, Y, 4, 12, and 21, we were able, in two cases, to trace the hidden near-haploid lines of approximately 5% and 20% of the cells, masked by hyperdiploid cells of approximately 80% and 70%, respectively; at relapse, the proportion was reversed, with predominant near-haploid lines of over 80% and residual hyperdiploidy of less than 10%. The near-haploid lines consisted of 24 and 27 chromosomes, and always retained the second copy of chromosome 21 or its derivative, as detected in one of our patients by SKY. The hyperdiploid clones were the exact duplicates of the near-haploid ones and contained four and two copies of the chromosomes represented in two and one copies in the near-haploid stem line, respectively. Unlike the common hyperdiploid ALL, no trisomies were observed. The patients were all aged >10 years, with WBC 0.7-30 x 10(9)/L, and a common ALL phenotype. They were treated with the ALL-BFM-95 protocol, medium risk group, and responded well to 8 days of steroid therapy, but relapsed early, within 11 months, and died a few months later. Interphase FISH technique is recommended for the detection of cryptic near-haploid clones in the diagnostic survey of ALL. To assess the prognostic value of near-haploidy in the context of the ALL-BFM protocols, a larger cohort of patients is required.
Subject(s)
Diploidy , Haploidy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Child , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Treatment OutcomeABSTRACT
A new conditional Egfr allele was used to dissect the roles of the receptor in eye development and to test two published models. EGFR function is necessary for morphogenetic furrow initiation, is not required for establishment of the founder R8 cell in each ommatidium, but is necessary to maintain its differentiated state. EGFR is required subsequently for recruitment of all other neuronal cells. The initial EGFR-dependent MAP kinase activation occurs in the furrow, but the active kinase (dp-ERK) is observed only in the cytoplasm for over 2 hours. Similarly, SEVENLESS-dependent activation results in cytoplasmic appearance of dp-ERK for 6 hours. These results suggest an additional regulated step in this pathway and we discuss models for this.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Drosophila Proteins , Drosophila/growth & development , Drosophila/metabolism , ErbB Receptors/metabolism , Eye/growth & development , Receptor Protein-Tyrosine Kinases , Alleles , Animals , Cell Nucleus/metabolism , Cytoplasm/metabolism , Drosophila/genetics , Enzyme Activation , ErbB Receptors/genetics , Eye Proteins/genetics , Eye Proteins/metabolism , Genes, Insect , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Microscopy, Confocal , Models, Biological , Mutation , Retina/growth & development , Retina/metabolism , TemperatureABSTRACT
The formation of the tracheal network in Drosophila is driven by stereotyped migration of cells from the tracheal pits. No cell divisions take place during tracheal migration and the number of cells in each branch is fixed. This work examines the basis for the determination of tracheal branch fates, prior to the onset of migration. We show that the EGF receptor pathway is activated by localized processing of the ligand SPITZ in the tracheal placodes and is responsible for the capacity to form the dorsal trunk and visceral branch. The DPP pathway, on the contrary, is induced in the tracheal pit by local presentation of DPP from the adjacent dorsal and ventral ectodermal cells. This pathway patterns the dorsal and lateral branches. Elimination of both pathways blocks migration of all tracheal branches. Antagonistic interactions between the two pathways are demonstrated. The opposing activities of two pathways may refine the final determination of tracheal branch fates.
Subject(s)
Drosophila Proteins , Drosophila/embryology , ErbB Receptors/physiology , Fibroblast Growth Factors , Insect Proteins/physiology , Protein-Tyrosine Kinases , Trachea/embryology , Animals , Cell Movement/genetics , Cell Movement/physiology , Drosophila/genetics , Drosophila/physiology , ErbB Receptors/genetics , Genes, Insect , Insect Proteins/genetics , Mutation , Phenotype , Receptors, Fibroblast Growth Factor/genetics , Receptors, Fibroblast Growth Factor/physiology , Trachea/cytology , Transcription Factors/genetics , Transcription Factors/physiologyABSTRACT
The thirty-ninth reported case of torsion of an intra-abdominal testicle is described in a neonate. The gonad was excised as is recommended because of the high incidence of malignancy (60of 37 cases). Torsion of an intra-abdominal testicle should be considered where an abdominal mass with calcification is found in an infant with undescended testis. Ultrasonography improves the diagnostic accuracy in infants because of the cystic nature of these masses in this age group.
Subject(s)
Humans , Male , Infant, Newborn , Cryptorchidism/complications , Spermatic Cord Torsion/complicationsABSTRACT
Receptor tyrosine kinases (RTKs) and the signaling cascades that they trigger play central roles in diverse developmental processes. We describe the capacity to follow the active state of these signaling pathways in situ. This is achieved by monitoring, with a specific monoclonal antibody, the distribution of the active, dual phosphorylated form of MAP kinase (ERK). A dynamic pattern is observed during embryonic and larval phases of Drosophila development, which can be attributed, to a large extent, to the known RTKs. This specific detection has enabled us to determine the time of receptor activation, visualize gradients and boundaries of activation, and postulate the distribution of active ligands. Since the antibody was raised against the phosphorylated form of a conserved ERK peptide containing the TEY motif, this approach is applicable to a wide spectrum of multicellular organisms.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Drosophila Proteins , Drosophila/embryology , Embryo, Nonmammalian/enzymology , Protein Kinases , Protein-Tyrosine Kinases , Receptor Protein-Tyrosine Kinases/metabolism , Animals , Drosophila/enzymology , Ectoderm/enzymology , Embryonic Development , Enzyme Activation , ErbB Receptors/metabolism , Ligands , Mesoderm/enzymology , Phosphorylation , Receptors, Fibroblast Growth Factor/metabolism , Receptors, Invertebrate Peptide/metabolism , Signal TransductionABSTRACT
Signaling cascades triggered by receptor tyrosine kinases (RTKs) participate in diverse developmental processes. The active state of these signaling pathways was monitored by examination of the in situ distribution of the active, dual phosphorylated form of mitogen-activated protein kinase (ERK) with a specific monoclonal antibody. Detection of the active state of the Drosophila epidermal growth factor receptor (DER) pathway allowed the visualization of gradients and boundaries of receptor activation, assessment of the distribution of activating ligands, and analysis of interplay with the inhibitory ligand Argos. This in situ approach can be used to monitor other receptor-triggered pathways in a wide range of organisms.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Drosophila Proteins , Drosophila/metabolism , Epidermal Growth Factor , ErbB Receptors/metabolism , Signal Transduction , Animals , Antibodies, Monoclonal , Body Patterning , Calcium-Calmodulin-Dependent Protein Kinases/immunology , Cell Differentiation , Drosophila/cytology , Drosophila/embryology , Drosophila/genetics , Eye Proteins/metabolism , Gene Expression Regulation, Developmental , Genes, Insect , Membrane Proteins/metabolism , Mutation , Nerve Tissue Proteins/metabolism , Phosphorylation , Photoreceptor Cells, Invertebrate/cytology , Photoreceptor Cells, Invertebrate/embryologySubject(s)
Drosophila Proteins , Drosophila/embryology , Embryo, Nonmammalian/physiology , Morphogenesis , Protein-Tyrosine Kinases , Animals , Basic Helix-Loop-Helix Transcription Factors , Body Patterning , Connexins/physiology , DNA-Binding Proteins/physiology , Embryo, Nonmammalian/cytology , Helix-Loop-Helix Motifs , Nerve Tissue Proteins/physiology , Receptors, Fibroblast Growth Factor/physiology , Trachea/cytology , Trachea/embryology , Transcription Factors/physiologyABSTRACT
A key step in development is the establishment of cell type diversity across a cellular field. Segmental patterning within the Drosophila embryonic epidermis is one paradigm for this process. At each parasegment boundary, cells expressing the Wnt family member Wingless confront cells expressing the homeoprotein Engrailed. The Engrailed-expressing cells normally differentiate as one of two alternative cell types. In investigating the generation of this cell type diversity among the 2-cell-wide Engrailed stripe, we previously showed that Wingless, expressed just anterior to the Engrailed cells, is essential for the specification of anterior Engrailed cell fate. In a screen for additional mutations affecting Engrailed cell fate, we identified anterior open/yan, a gene encoding an inhibitory ETS-domain transcription factor that is negatively regulated by the Rasl-MAP kinase signaling cascade. We find that Anterior Open must be inactivated for posterior Engrailed cells to adopt their correct fate. This is achieved by the EGF receptor (DER), which is required autonomously in the Engrailed cells to trigger the Ras1-MAP kinase pathway. Localized activation of DER is accomplished by restricted processing of the activating ligand, Spitz. Processing is confined to the cell row posterior to the Engrailed domain by the restricted expression of Rhomboid. These cells also express the inhibitory ligand Argos, which attenuates the activation of DER in cell rows more distant from the ligand source. Thus, distinct signals flank each border of the Engrailed domain, as Wingless is produced anteriorly and Spitz posteriorly. Since we also show that En cells have the capacity to respond to either Wingless or Spitz, these cells must choose their fate depending on the relative level of activation of the two pathways.
Subject(s)
Drosophila Proteins , Drosophila/genetics , Epidermal Growth Factor , Epidermis/growth & development , Homeodomain Proteins/metabolism , Membrane Proteins/metabolism , Protein Kinases , Proto-Oncogene Proteins/metabolism , Repressor Proteins , Transcription Factors/metabolism , Animals , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila/growth & development , Embryonic Induction/genetics , ErbB Receptors/genetics , ErbB Receptors/metabolism , Eye Proteins/genetics , Eye Proteins/metabolism , Homeodomain Proteins/genetics , Membrane Proteins/genetics , Mutation , Proto-Oncogene Proteins/genetics , Receptors, Invertebrate Peptide/genetics , Receptors, Invertebrate Peptide/metabolism , Transcription Factors/genetics , Wnt1 ProteinABSTRACT
The thirty-ninth reported case of torsion of an intra-abdominal testicle is described in a neonate. The gonad was excised as is recommended because of the high incidence of malignancy (60% of 37 cases). Torsion of an intra-abdominal testicle should be considered where an abdominal mass with calcification is found in an infant with undescended testis. Ultrasonography improves the diagnostic accuracy in infants because of the cystic nature of these masses in this age group.
Subject(s)
Cryptorchidism/complications , Spermatic Cord Torsion/complications , Humans , Infant, Newborn , MaleABSTRACT
The induction of different cell fates along the dorsoventral axis of the Drosophila embryo requires a graded activity of the EGF receptor tyrosine kinase (DER). Here we have identified primary and secondary target genes of DER, which mediate the determination of discrete ventral cell fates. High levels of DER activation in the ventralmost cells trigger expression of the transcription factors encoded by ventral nervous system defective (vnd) and pointed P1 (pntPl). Concomitant with the induction of pntP1, high levels of DER activity lead to inactivation of the Yan protein, a transcriptional repressor of Pointed-target genes. These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan. The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates.
Subject(s)
Drosophila Proteins , Drosophila melanogaster/embryology , ErbB Receptors/physiology , Gene Expression Regulation, Developmental , Receptor Protein-Tyrosine Kinases/physiology , Repressor Proteins , Transcription Factors/physiology , Animals , DNA-Binding Proteins/physiology , Ectoderm/physiology , Eye Proteins/physiology , In Situ Hybridization , Morphogenesis , Nerve Tissue Proteins , Proto-Oncogene Proteins/physiology , Signal Transduction , Transcription, GeneticABSTRACT
In the absence of efficient transcription termination correct 3'-end processing is an essential step in the synthesis of stable chloroplast mRNAs in higher plants. We show here that 3'-end processing in vitro involves endonucleolytic cleavage downstream from the mature terminus, followed by exonucleolytic processing to a stem-loop within the 3'-untranslated region. These processing steps require a high molecular weight complex that contains both endoribonucleases and an exoribonuclease. In the presence of ancillary RNA binding proteins the complex correctly processes the 3'-end of precursor RNA. In the absence of these ancillary proteins 3'-end maturation is prevented and plastid mRNAs are degraded. Based on these results we propose a novel mechanism for the regulation of mRNA 3'-end processing and stability in chloroplasts.
Subject(s)
Chloroplasts/metabolism , Cytochrome b6f Complex , Plant Proteins/metabolism , RNA, Messenger/metabolism , RNA, Plant/metabolism , RNA-Binding Proteins/metabolism , Amino Acid Sequence , Cytochrome b Group/genetics , Endoribonucleases/metabolism , Molecular Sequence Data , Molecular Weight , Plastids/metabolism , Polyribonucleotide Nucleotidyltransferase/genetics , Polyribonucleotide Nucleotidyltransferase/metabolism , RNA Processing, Post-Transcriptional , Ribonucleoproteins/chemistry , Ribonucleoproteins/genetics , Ribonucleoproteins/metabolism , Sequence Homology, Amino Acid , Spinacia oleracea/genetics , Spinacia oleracea/metabolismABSTRACT
Homozygous sickle-cell (SS) disease is associated with retardation of physical and sexual development but most Jamaican SS children commence their adolescent growth spurt before 16 years of age. Analysis of growth data from children in the Jamaican Cohort Study noted extreme growth retardation, defined as absence of the adolescent growth spurt and pre-pubertal sexual development (Tanner stage 1 or 2) at age 16 years, in 8/52 (15%) SS boys. These and two boys from the general sickle-cell clinic with a similar growth pattern provided a study group of 10 boys who were investigated for a possible endocrine explanation for their extreme retardation of physical maturation. A sub-optimal testosterone response (< 10 nmol/l) to human chorionic gonadotrophin and an exaggerated gonadotrophin response to gonadotrophin hormone releasing hormone was consistent with poor testicular function in 5 boys. Retardation of adolescent growth and development is common in boys with SS disease but, when extreme, requires early investigation to identify potentially correctable mechanisms.
Subject(s)
Anemia, Sickle Cell/genetics , Homozygote , Puberty, Delayed/genetics , Testosterone/deficiency , Adolescent , Anthropometry , Child , Cohort Studies , Energy Metabolism/genetics , Hormones/blood , Humans , Jamaica , MaleABSTRACT
This paper describes a 9-year-old girl with primary hypophosphatemic rickets, an uncommon cause of bowed legs. A simple screening for patients presenting with bowed legs is suggested and the importance of using age-related standards for comparison of biochemical results is emphasized.