A testicular tumor in a 12- year-old boy proved to be a carcinoid tumor. An extensive investigation including a computed tomographic scan of the abdominal and pelvic region as well as both 123I-labeled metaiodobenzylg...A testicular tumor in a 12- year-old boy proved to be a carcinoid tumor. An extensive investigation including a computed tomographic scan of the abdominal and pelvic region as well as both 123I-labeled metaiodobenzylguanidine and 111In-coupled octreotide scintigraphy was normal. Because histopathologic examination of the primary surgical specimen revealed tumor growth in the resection border of the spermatic vessels, a second operation with unilateral lymph node dissectionwas performed. Surprisingly, 3 lymph node metastases were found. No further treatment was given and the boy is alive without disease 9 years after surgery. This case illustrates that modern scintigraphic techniques do not always detect carcinoid tumors. Because carcinoids respond poorly to other treatment modalities, the importance of initial radical surgery including a meticulous examination of regional lymph nodes is emphasized.展开更多
Background: Guidelines recommend preventive medications for all children with persistent asthma, yet young urban children often receive inadequate therapy. Th is may occur in part because primary care providers are un...Background: Guidelines recommend preventive medications for all children with persistent asthma, yet young urban children often receive inadequate therapy. Th is may occur in part because primary care providers are unaware of the severity of their patients’symptoms. Objective: To determine whether systematic school- based asthma screening, coupled with primary care provider notification of asthm a severity, will prompt providers to take preventive medication action (prescribe a new preventive medication or change a current d ose). Design: Children aged 3 to 7 years with mild persistent to severe persiste nt asthma were identified at the start of the 2002-2003 school year in Rocheste r. Children were assigned randomly to a provider notification group (child’s pr imary care provider notified of asthma severity) or a control group (provider no t notified of severity). Primary care providers of children in the provider noti fication group were sent a facsimile indicating the child’s symptoms and recomm ending medication action based on national criteria. Interviewers blinded to the child’s group assignment called parents 3 to 6 months later to determine if pr eventive actions were taken. Results: Of 164 eligible children with mild persist ent or more severe asthma, 151 (92.1%) were enrolled. Children in the provider notification group were not more likely to receive a preventive medication actio n than were children in the control group (21.9%vs 26.0%; P=.57). Additional p reventive measures, including encouraging compliance with medications (33.3%vs 31.3%; P=.85), recommending environmental modifications (39.3%vs 42.4%; P=.86 ), and referrals for specialty care (6.6%vs 6.0%; P>.99), also did not differ between the provider notification and control groups. At the end of the study, 5 2.4%of children in both groups with no medication changes were still experienci ng persistent symptoms. Conclusions: School-based asthma screening identified m any symptomatic children in need of medication modification. Provider notificati on, however, did not improve preventive care. Findings suggest that more powerfu l interventions are needed to make systematic asthma screening effective.展开更多
Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse form...Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.展开更多
文摘A testicular tumor in a 12- year-old boy proved to be a carcinoid tumor. An extensive investigation including a computed tomographic scan of the abdominal and pelvic region as well as both 123I-labeled metaiodobenzylguanidine and 111In-coupled octreotide scintigraphy was normal. Because histopathologic examination of the primary surgical specimen revealed tumor growth in the resection border of the spermatic vessels, a second operation with unilateral lymph node dissectionwas performed. Surprisingly, 3 lymph node metastases were found. No further treatment was given and the boy is alive without disease 9 years after surgery. This case illustrates that modern scintigraphic techniques do not always detect carcinoid tumors. Because carcinoids respond poorly to other treatment modalities, the importance of initial radical surgery including a meticulous examination of regional lymph nodes is emphasized.
文摘Background: Guidelines recommend preventive medications for all children with persistent asthma, yet young urban children often receive inadequate therapy. Th is may occur in part because primary care providers are unaware of the severity of their patients’symptoms. Objective: To determine whether systematic school- based asthma screening, coupled with primary care provider notification of asthm a severity, will prompt providers to take preventive medication action (prescribe a new preventive medication or change a current d ose). Design: Children aged 3 to 7 years with mild persistent to severe persiste nt asthma were identified at the start of the 2002-2003 school year in Rocheste r. Children were assigned randomly to a provider notification group (child’s pr imary care provider notified of asthma severity) or a control group (provider no t notified of severity). Primary care providers of children in the provider noti fication group were sent a facsimile indicating the child’s symptoms and recomm ending medication action based on national criteria. Interviewers blinded to the child’s group assignment called parents 3 to 6 months later to determine if pr eventive actions were taken. Results: Of 164 eligible children with mild persist ent or more severe asthma, 151 (92.1%) were enrolled. Children in the provider notification group were not more likely to receive a preventive medication actio n than were children in the control group (21.9%vs 26.0%; P=.57). Additional p reventive measures, including encouraging compliance with medications (33.3%vs 31.3%; P=.85), recommending environmental modifications (39.3%vs 42.4%; P=.86 ), and referrals for specialty care (6.6%vs 6.0%; P>.99), also did not differ between the provider notification and control groups. At the end of the study, 5 2.4%of children in both groups with no medication changes were still experienci ng persistent symptoms. Conclusions: School-based asthma screening identified m any symptomatic children in need of medication modification. Provider notificati on, however, did not improve preventive care. Findings suggest that more powerfu l interventions are needed to make systematic asthma screening effective.
基金supported by research grants from the National Natural Science Foundation of China(31671510 and 31871461 to H.H.31771592 to W.X.)。
文摘Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.
