RESUMO
Beare-Stevenson cutis gyrata syndrome (MIM 123790) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Many of these features are characteristic of some of the autosomal dominant craniosynostotic syndromes. Mutations in Crouzon, Jackson-Weiss, Pfeiffer and Apert syndromes have been reported in the FGFR2 extracellular domain. In Crouzon syndrome patients with acanthosis nigricans, a recurrent mutation occurs in the transmembrane domain of FGFR3. We now describe the detection of FGFR2 mutations in the Beare-Stevenson cutis gyrata syndrome. In three sporatic cases, a novel missense mutation was found causing an amino acid to be replaced by a cysteine; two had the identical Ty375Cys mutation in the transmembrane domain and one had a Ser372Cys mutation in the carboxyl-terminal end of the linker region between the immunoglobulin III-like (Iglll) and transmembrane domains. In two patients, neither of these mutations were found suggesting further genetic heterogeneity.
Assuntos
Anormalidades Múltiplas/genética , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética , Anormalidades da Pele , Acantose Nigricans/genética , Sequência de Aminoácidos , Sequência de Bases , Craniossinostoses/genética , Primers do DNA/química , Éxons , Feminino , Genes Dominantes , Humanos , Masculino , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Linhagem , Mutação Puntual , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , SíndromeRESUMO
Addition of lysergic acid diethylamide to cultured human leukocytes resulted in a marked increase of chromosomal abnormalities. The distribution of chromosome breaks deviated significantly from random, with an accumulation of aberrations in chromosome No. 1. Cytogenetic investigation of a patient extensively treated with this drug over a 4-year period for paranoid schizophrenia showed a similar increase in chromosomal damage.
Assuntos
Aberrações Cromossômicas/induzido quimicamente , Cromossomos/efeitos dos fármacos , Leucócitos/citologia , Dietilamida do Ácido Lisérgico/farmacologia , Transtornos Cromossômicos , Técnicas de Cultura , Citogenética , Humanos , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológicoRESUMO
Bleomycin exposure evoked a specific sensitivity in five ataxia telangiectasia (AT) long-term lymphoblastoid cell lines when compared to lines derived from four normal individuals or three patients with xeroderma pigmentosum. At all concentrations tested or after each treatment regimen, statistically significant differences in viability and cytogenetic damage were obvious, with the AT cell lines demonstrating reduced survival and increased chromosomal breakage. However, similar differences were not observed following treatment of all cell lines with mitomycin C. The normal and xeroderma pigmentosum cells appear capable of overcoming the effects of bleomycin during a 48- or 72-hr recovery period while the AT cell lines could not. This specific response to bleomycin constitutes the first demonstration of increased chromosome breakage in vitro in long-term AT lymphoblastoid cell lines.
Assuntos
Ataxia Telangiectasia/genética , Bleomicina/toxicidade , Aberrações Cromossômicas , Reparo do DNA , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromossomos Humanos/efeitos dos fármacos , Humanos , Linfócitos/efeitos dos fármacosRESUMO
31P nuclear magnetic resonance (NMR) studies were conducted on perchloric acid extracts of the brain of one control, two Huntington's disease (HD), one probable Alzheimer's disease (AD), and one AD patient. These studies demonstrated significant elevations (over control) in the levels of phosphomonoesters in all brain areas of the patients with HD and AD even in areas devoid of neuropathological findings. Elevations of phosphodiesters were also observed, but they tended to reflect the degree of neuropathological change. We postulate that the 31P NMR findings represent molecular alterations with corresponding metabolic correlates which either antedate or occur in the absence of changes in cellular morphology or structure. As such the 31P NMR findings may reflect a subcellular "molecular neuropathology."
Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Glicerofosfatos/metabolismo , Doença de Huntington/metabolismo , Adulto , Idoso , Animais , Etanolaminas/metabolismo , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , CoelhosRESUMO
Programmed cell death is a physiological process in mammalian development by which specific types of cells are eliminated, and, hence, is of fundamental importance in normal human embryogenesis. A patient is described with multiple congenital anomalies that may be explained by a disturbance of programmed cell death. Anomalies included macrocephaly, hypoplastic lacrimal ducts, narrow external ear canals, pharyngeal mucous membrane fold, unilateral cryptorchidism, cord-like vasa deferentia, and complete cutaneous syndactyly of the hands and feet.
Assuntos
Anormalidades Múltiplas/etiologia , Apoptose/fisiologia , Anormalidades Múltiplas/fisiopatologia , Adulto , Humanos , MasculinoRESUMO
We examined three patients with a chiasmal syndrome due to metastasis and were able to find only two additional cases in the literature. The characteristic presentation consisted of progressive impairment of vision without headache or abnormal plain skull x-ray films in patients with weight loss or diabetes insipidus. In three of the five patients, the primary malignant neoplasm was occult when symptoms and signs of chiasmal dysfunction were seen. Four patients responded well to irradiation. The chiasm may be compromised by suprasellar extension of pituitary metastasis, by infiltration from an infundicular or hypothalamic metastasis, or by hematogenous spread of tumor.
Assuntos
Neoplasias Encefálicas/complicações , Neoplasias dos Nervos Cranianos/complicações , Quiasma Óptico , Escotoma/etiologia , Transtornos da Visão/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , SíndromeRESUMO
Retraction of the lower eyelid is a useful sign of disease. It is an early manifestation of weakness of the facial muscles, occurring with myopathies, myasthenia, and upper and lower motor neuron facial paresis. Rarely, lower and upper lid retraction occur without proptosis in patients with Graves disease. Lower lid retraction occurs in proptosis and varies directly with the degree of proptosis. It is also seen with senile entropion or ectropion, after eye muscle or orbital surgery, and with contraction of lid tissues. Apparent retraction results when the contralateral lower lid is pathologically elevated, as in Horner syndrome, in enophthalmos, or with vertical deviations of the eye.
Assuntos
Pálpebras/fisiopatologia , Exoftalmia/fisiopatologia , Doença de Graves/fisiopatologia , Humanos , Hipotonia Muscular/fisiopatologia , Estrabismo/fisiopatologiaRESUMO
Three adults with acquired unilateral visual impairment noticed phosphenes when they heard noises. They witnessed them only when resting in a dark or dimly illuminated room. The hallucinations persisted for days in a postkeratoplasty patient, for weeks in a patient with optic neuritis, and for months in a patient with compression of the optic nerve. The sound-induced phosphenes in these cases seemed to be a pathologic variety of hypnagogic hallucination. We theorize that under conditions of altered excitability and visual deafferentation of the brain, cells capable of responding to both visual and auditory stimuli become hyperresponsive to sounds.
Assuntos
Estimulação Acústica , Alucinações/fisiopatologia , Fosfenos , Visão Ocular , Adulto , Encéfalo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We prospectively studied 60 patients with uncomplicated optic neuritis (ON) to determine the risk of subsequent multiple sclerosis (MS). All patients were followed for at least 5 years (mean, 7.1 years). Seventeen patients (28 percent) developed definite MS and four (7 percent) developed probable or possible MS. Six of the 17 patients who developed definite MS did so within the first year. Forty-five percent of the women but only 11 percent of the men developed MS. Both sexes were at highest risk if the ON occurred between the ages of 21 and 40. Fifty-one percent of patients in this age group progressed to MS, whereas the risk for others was 12 percent. There was an overall increased risk of MS with recurrent ON. The course of the MS appeared to be benign during the period of observation.
Assuntos
Esclerose Múltipla/etiologia , Neurite Óptica/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Fatores Sexuais , Acuidade VisualRESUMO
Normal gerbils and those made ischemic for 15 to 60 minutes by bilateral common carotid artery occlusion were studied ultrastructurally after administration of the vasoactive drug pentoxifylline. In both groups, hypertrophy of neuronal mitochondria was found in the hippocampus and cerebral cortex. Planimetry of electron micrographs revealed a statistically significant increase in average mitochondrial size of drug-treated animals compared with untreated ischemic gerbils and normal controls; the treated ischemic group showed the greatest increase. Incubated cortical slices from normal gerbils that were given the drug 5 hours before they were killed showed a significant increase in oxygen consumption compared with controls.
Assuntos
Encéfalo/irrigação sanguínea , Córtex Cerebral/ultraestrutura , Hipocampo/ultraestrutura , Isquemia/tratamento farmacológico , Pentoxifilina/farmacologia , Teobromina/análogos & derivados , Animais , Córtex Cerebral/efeitos dos fármacos , Feminino , Gerbillinae , Hipocampo/efeitos dos fármacos , Isquemia/mortalidade , Isquemia/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Pentoxifilina/uso terapêutico , Polirribossomos/ultraestrutura , Tratos Piramidais/efeitos dos fármacos , Tratos Piramidais/ultraestruturaRESUMO
An 18 year old phenotypic man is described with chromatin-positive Klinefelter's syndrome and undetectable peripheral human follicle stimulating hormone levels. The subject manifested chromosomal mosaicism consisting of three stem cell lines (45X; 46XY; and 47XXY). Testicular biopsy specimen showed germinal cell aplasia: the tubules were lined by Sertoli cells only, whereas the Leydig cells appeared normal. Serum human follicle stimulating hormone levels were undetectable and rose to only 5 mIU/ml after the administration of luteinizing hormone releasing hormone. Serum human luteinizing hormone varied between normal and moderately elevated values, and serum testosterone was in the low normal range. We discuss the features which distinguish this syndrome from isolated gonadotropin deficiency and from classic germinal cell aplasia. We suggest that the patient represents a new variant of Klinefelter's syndrome, with failure of human follicle stimulating hormone release secondary to prolonged hypersecretion.
Assuntos
Hormônio Foliculoestimulante/sangue , Síndrome de Klinefelter/genética , Adolescente , Biópsia , Hormônio do Crescimento/sangue , Humanos , Síndrome de Klinefelter/sangue , Síndrome de Klinefelter/fisiopatologia , Células Intersticiais do Testículo , Hormônio Luteinizante/sangue , Masculino , Mosaicismo , Fenótipo , Células de Sertoli , Cromatina Sexual , Testículo/patologia , Testosterona/sangueRESUMO
1. The initial response after endotoxin administration (3 mg/kg) in cats involved pulmonary vasoconstriction. This was not seen when endotoxin was given by slow infusion and it could be prevented after a bolus injection of endotoxin by pretreatment of the cats with aspirin (10 mg/kg). Intense mesenteric vasoconstriction occurred in all the cats.2. The mesenteric vasoconstriction was a specific response of the mesenteric blood vessels. At the time the mesenteric bed constricted, the renal bed dilated, the hepatic arterial bed remained unchanged and the smooth muscle of the intestinal wall relaxed.3. Arterial blood from cats with a fully developed mesenteric vasoconstriction after endotoxin administration was perfused through a normal intestine. No immediate vasoconstriction developed but the perfused intestine constricted slowly over 60 minutes. This suggests that mesenteric constriction was not due to circulating vasoconstrictor factors or the intestinal innervation, but involved a slow local mechanism within the intestine. It could not be prevented or reversed by a variety of pharmacological agents.4. These observations suggest that endotoxin caused a unique type of mesenteric vasoconstriction in cats by a local mechanism which took up to 60 min to develop, was sufficiently potent to reduce mesenteric flow to <30% control, and was maintained until death of the cats. Blood from these animals did not clot when placed in a glass tube.5. The mesenteric constriction and the clotting defect could be prevented by repeated administration of aminophylline and dextran solution before and after a bolus intravenous injection of endotoxin. Arterial pressure and mesenteric flow were maintained for at least 10 h in these experiments. Inadequate treatment intensified rather than reduced the intestinal mucosal damage.6. Cats were treated with aspirin, endotoxin and the optimal regimen for prevention of the mesenteric constriction and allowed to recover from the anaesthetic agent. In this series, 63% survived indefinitely compared to 25% after aspirin and endotoxin treatment and 0% after endotoxin alone.7. The possible mechanisms of action of aspirin and aminophylline-dextran solution are discussed. Our failure to obtain 100% survival is probably due to pulmonary damage which develops 10-24 h after endotoxin administration. This delayed pulmonary action of endotoxin is not prevented by aspirin treatment and it seems unlikely that aspirin will be of any value in the treatment of the pulmonary lesion in man.
Assuntos
Transtornos da Coagulação Sanguínea/induzido quimicamente , Endotoxinas/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Aminofilina/farmacologia , Animais , Aspirina/farmacologia , Peso Corporal , Gatos , Dextranos/farmacologia , Endotoxinas/antagonistas & inibidores , Epinefrina/farmacologia , Heparina/farmacologia , Artéria Hepática/efeitos dos fármacos , Infusões Parenterais , Intestinos/efeitos dos fármacos , Isoproterenol/farmacologia , Rim/efeitos dos fármacos , Mesentério/efeitos dos fármacos , Músculo Liso/efeitos dos fármacosRESUMO
Administrative data have not been used extensively for case-control studies. As an example, data from the Manitoba Health Services Commission were used to assess the effectiveness of Papanicolaou (Pap) testing in screening for cancer of the cervix. Case patients were 415 women with invasive cancer (aged 25 to 64 years) from the Manitoba Cancer Registry and control subjects were women aged 25 to 64 years chosen from a random sample of the Manitoba female population (N = 29,926). For 82% of case patients there was information about Pap testing in a prior 5-year period, as compared to 91% of the controls. Since diagnostic tests could not be distinguished from screening tests, data for the year prior to diagnosis were not used. The odds ratios for Pap testing reducing the risk of cancer of the cervix was 0.82 (95% confidence interval [CI]: 0.53, 1.26) for women aged 25 to 34, 0.55 (95% CI: 0.35, 0.85) for women aged 35 to 44, 0.40 (95% CI: 0.23, 0.69) for women aged 45 to 54, and 0.45 (95% CI: 0.26, 0.78) for women aged 55 to 64. The overall 4-year relative odds adjusted for age and number of physician visits was 0.51 (95% CI: 0.43, 0.61). These results were similar to previously published values obtained from interview studies. Selection and recall bias are minimized and using claims avoids the expense of seeking neighborhood control subjects, carrying out interviews, or performing follow-up searches. As well, true population-based controls can be used.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Programas Nacionais de Saúde/organização & administração , Teste de Papanicolaou , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Adulto , Estudos de Casos e Controles , Métodos Epidemiológicos , Feminino , Humanos , Manitoba/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
The Hallermann-Streiff syndrome is characterized by dyscephaly, hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, and proportionate short stature. Cause is unknown; sporadic occurrence is the rule. Data presented in this review include the characteristics of pregnancy, growth and development, principal manifestations, radiographic and ophthalmological characteristics, and the results of cephalometric study. Potential complications in the syndrome are related to the narrow upper airway associated with the craniofacial configuration. Severe complications may include early pulmonary infection, respiratory embarrassment, obstructive sleep apnea, and anesthetic risk. Topics for future study are suggested.
Assuntos
Síndrome de Hallermann/diagnóstico , Adolescente , Adulto , Anestesia/efeitos adversos , Cefalometria , Pré-Escolar , Diagnóstico Diferencial , Feminino , Transtornos do Crescimento/complicações , Síndrome de Hallermann/complicações , Síndrome de Hallermann/etiologia , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/complicações , Masculino , Pneumonia/complicações , Insuficiência Respiratória/complicaçõesRESUMO
Further evidence for a diagnosis of the Elephant Man's condition is reviewed. It is known that the Elephant Man had "mocassin" lesions, hyperostoses of the skull, and absence of café-au-lait spots, all of which are characteristic of Proteus syndrome. Recently, questions have been raised about his skeletal findings and their relevance to neurofibromatosis. However, other skeletal diagnoses have been entertained, including Maffucci syndrome, Paget's disease of bone, pyarthrosis, and fibrous dysplasia. These diagnostic possibilities are discussed and evaluated critically. It is concluded that the skeletal findings are most consistent with Proteus syndrome and coincidental hip disease secondary to childhood trauma.
Assuntos
Neurofibromatose 1/diagnóstico , Diagnóstico Diferencial , História do Século XIX , História do Século XX , Humanos , Masculino , Neurofibromatose 1/genética , Neurofibromatose 1/história , SíndromeRESUMO
The purpose of this paper is to provide a new perspective on craniosynostosis by correlating what is known about sutural biology with the events of craniosynostosis per se. A number of key points emerge from this analysis: 1) Sutural initiation may take place by overlapping, which results in beveled sutures, or by end-to-end approximation, which produces nonbeveled, end-to-end sutures. All end-to-end sutures occur in the midline (e.g., sagittal and metopic) probably because embryonic biomechanical forces on either side of the initiating suture tend to be equal in magnitude. A correlate appears to be that only synostosed sutures of the midline have pronounced bony ridging. 2) Long-term histologic observations of the sutural life cycle call into question the number of layers within sutures. The structure varies not only in different sutures, but also within the same suture over time. 3) Few, if any, of the many elegant experimental research studies in the field of sutural biology have increased our understanding of craniosynostosis per se. An understanding of the pathogenesis of craniosynostosis requires a genetic animal model with primary craniosynostosis and molecular techniques to understand the gene defect. This may allow insight into pathogenetic mechanisms involved in primary craniosynostosis. It may prove to be quite heterogeneous at the basic level. 4) The relationship between suture closure, cessation of growth, and functional demands across sutures poses questions about various biological relationships. Two conclusions are provocative. First, cessation of growth does not necessarily, or always lead to fusion of sutures. Second, although patent sutures aid in the growth process, some growth can take place after suture closure. 5) In an affected suture, craniosynostosis usually begins at a single point and then spreads along the suture. This has been shown by serial sectioning and calls into question results of studies in which the affected sutures are only histologically sampled. 6) Craniosynostosis is etiologically and pathogenetically heterogeneous. Known human causes are reviewed. Is craniosynostosis simply normal suture closure commencing too early?(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Suturas Cranianas/crescimento & desenvolvimento , Craniossinostoses/patologia , Adulto , Idoso , Animais , Fenômenos Biomecânicos , Suturas Cranianas/anatomia & histologia , Suturas Cranianas/fisiologia , Craniossinostoses/etiologia , Craniossinostoses/genética , Feminino , Humanos , Recém-Nascido , Masculino , Camundongos , Pessoa de Meia-Idade , LinhagemRESUMO
I report 2 unusual cases of Proteus syndrome that support the concept of somatic mosaicism. In one patient, a huge connective tissue nevus covered the chest and abdomen and hyperostoses of the calvaria were observed. In the other patient, linear verrucous epidermal nevi, epibulbar dermoids, and hyperostoses were found. No enlargement of the limbs or digits occurred and the plantar surfaces of the feet were normal. Selective aspects of Proteus syndrome not previously reviewed are also presented including: uncommon neoplasms; pulmonary and renal abnormalities; brain malformations; facial phenotype associated with seizures and severe mental deficiency; and types of abnormal growth in the craniofacial skeleton.
Assuntos
Mosaicismo , Síndrome de Proteu/genética , Encéfalo/anormalidades , Pré-Escolar , Doenças do Tecido Conjuntivo/genética , Doenças do Tecido Conjuntivo/patologia , Hamartoma/genética , Hamartoma/patologia , Humanos , Hiperostose/genética , Hiperostose/patologia , Deficiência Intelectual/genética , Rim/anormalidades , Pulmão/anormalidades , Masculino , Neoplasias/genética , Fenótipo , Síndrome de Proteu/patologia , Dermatopatias/genética , Dermatopatias/patologiaRESUMO
This paper attempts to balance our knowledge of holoprosencephalic spectra and continuities with important distinctions and discontinuities. Prevalence studies and syndrome delineation are briefly reviewed. The following topics receive detailed coverage: human teratogens, special aspects of forebrain and hindbrain malformations, aprosencephaly/atelencephaly, association with neural tube defects, current assessment of "facial principles," and endocrine abnormalities.
Assuntos
Anormalidades Múltiplas/epidemiologia , Encéfalo/anormalidades , Ossos Faciais/anormalidades , Humanos , Prevalência , Síndrome , TeratogênicosRESUMO
This overview of asymmetry addresses the following topics: chiral molecules; asymmetric signaling molecules, including N-cadherin, Shh, Fgf8, lefty1, lefty2, nodal, Pitx2, activin betaB, activin receptor IIA, and cSnR; situs abnormalities; asymmetric cell division; laterality in humans and animals; behavioral asymmetry in humans and animals; asymmetric embryopathies, including Tessier-type "clefts"; hemiasymmetries such as hemihyperplasia, hemihypoplasia, and hemiatrophy; asymmetric vascular syndromes, including Klippel-Trenaunay and Sturge-Weber syndromes; plagiocephaly of the synostotic and deformational types; somatic mosaicism, including a discussion of McCune-Albright syndrome, fibrous dysplasia, GNAS1 mutations, and Proteus syndrome.
Assuntos
Anormalidades Congênitas/genética , Animais , Padronização Corporal/genética , Divisão Celular/genética , Anormalidades Congênitas/embriologia , Anormalidades Congênitas/patologia , Anormalidades do Olho/embriologia , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Regulação da Expressão Gênica , HumanosRESUMO
The decline in frog populations and the increase in the frequency of frog malformations are discussed. Topics considered for analysis include chytridiomycosis, retinoids, UV-B radiation, chemical contaminants, environmental threats, introduced invasive species and predation, unsustainable use, and enigmatic decline. Care must be taken to distinguish between hypotheses, laboratory experiments, and the findings in feral frog populations. Clearly, the causes of population decline and malformations are heterogeneous. The subject of frogs and humans is addressed under three subheadings: the importance of frogs to human societies, medical implications of frog studies, and a comparison of frog and human disease factors.