Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadot...Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nlCH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.展开更多
As the increase in lifespan brings to light diseases that were previously not clinically detectable,osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones b...As the increase in lifespan brings to light diseases that were previously not clinically detectable,osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense,fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors,osteoporosis presents a multifactorial etiopathogenesis,with the genetic component accounting for 70% of an individual variation in bone mass density (BMD),the principal determinant,with age,of fracture risk. Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss,so that the occurrence of osteoporosis in celiac subjects is of particular note: indeed,the screening of osteoporosis patients for this disease is advisable,since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β,of the IL-1 system,in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea,and it may follow prolonged breast-feeding and frequent pregnancies,while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards,together with early diagnosis of and treatment for CD and primary and secondary endocrine pathologies are important for the prevention of damage to the bones.展开更多
Brassinosteroids (BRs) are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its k...Brassinosteroids (BRs) are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its kinase activity has an essential role in BR-regulated plant growth and development. Here we report the isolation and molecular characterization of a new allele of bril, bril-301, which shows moderate morphological phenotypes and a reduced response to BRs under normal growth conditions. Sequence analysis identified a two-base alteration from GG to AT, resulting in a conversion of 989G to 9891 in the BRI1 kinase domain. An in vitro assay of kinase activity showed that bril-301 has no detectable autophosphorylation activity or phosphorylation activity towards the BRI1 substrates TTL and BAK1. Furthermore, our results suggest that bril-301, even with extremely impaired kinase activity, still retains partial function in regulating plant growth and development, which raises the question of whether BRI1 kinase activity is essential for BR-mediated growth and development in higher plants.展开更多
AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric ...AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.展开更多
Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spre...Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spreading moxibustion group and a Western medicine group by the random number table method,with 30 cases in each group.The Western medicine group was treated with climen,starting from the 5th day of the menstrual cycle for 21 d.The spreading moxibustion group was treated with herb-partitioned spreading moxibustion at Baliao points on the basis of the medication in the Western medicine group,1 h per time,once a week.The treatment was performed for 1 month as one treatment course in both groups,for 3 courses in total.The serum follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)in the patients were measured before and after treatment.The peak systolic velocity(PSV)and resistance index(RI)were also detected.The traditional Chinese medicine(TCM)symptom score was evaluated.The clinical efficacy was evaluated after treatment.Results:The total effective rate in the spreading moxibustion group was 93.3%,which was significantly higher than 80.0%in the Western medicine group,and the difference between the groups was statistically significant(P<0.05).After treatment,the TCM symptom scores,the serum FSH levels,FSH/LH ratios and RI in both groups decreased,and the intra-group differences were all statistically significant(all P<0.05).The serum E2 level and PSV increased compared with those in the same group before treatment,and the intra-group differences were statistically significant(all P<0.05).After treatment,the TCM symptom score,the serum FSH level,FSH/LH ratio and RI in the spreading moxibustion group were lower than those in the Western medicine group,while the serum E2 level and PSV were higher than those in the Western medicine group,and the differences between the groups were statistically significant(all P<0.05).Conclusion:Herb-partitioned spreading moxibustion at Baliao points plus climen can produce valid therapeutic efficacy for DOR.It can improve the clinical symptoms,regulate serum hormone levels and increase ovarian blood perfusion,thus improving ovarian reserve function,producing more significant efficacy than climen alone.展开更多
文摘Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nlCH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.
基金Progetto di ricerca (2006-2008):"Rischio genotossico nella fi liera alimentare", Responsabile:Dr.Riccardo Crebelli, Istituto Superiore di Sanità, Italy
文摘As the increase in lifespan brings to light diseases that were previously not clinically detectable,osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense,fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors,osteoporosis presents a multifactorial etiopathogenesis,with the genetic component accounting for 70% of an individual variation in bone mass density (BMD),the principal determinant,with age,of fracture risk. Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss,so that the occurrence of osteoporosis in celiac subjects is of particular note: indeed,the screening of osteoporosis patients for this disease is advisable,since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β,of the IL-1 system,in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea,and it may follow prolonged breast-feeding and frequent pregnancies,while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards,together with early diagnosis of and treatment for CD and primary and secondary endocrine pathologies are important for the prevention of damage to the bones.
基金We thank Prof Joanne Chory (The Salk Institute for Biological Studies, USA) for providing the Arabidopsis bril-101 mutant seeds. This work was supported by grants from the National Natural Science Foundation of China (grant numbers: 30070074, 30330040 and 30570161).
文摘Brassinosteroids (BRs) are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its kinase activity has an essential role in BR-regulated plant growth and development. Here we report the isolation and molecular characterization of a new allele of bril, bril-301, which shows moderate morphological phenotypes and a reduced response to BRs under normal growth conditions. Sequence analysis identified a two-base alteration from GG to AT, resulting in a conversion of 989G to 9891 in the BRI1 kinase domain. An in vitro assay of kinase activity showed that bril-301 has no detectable autophosphorylation activity or phosphorylation activity towards the BRI1 substrates TTL and BAK1. Furthermore, our results suggest that bril-301, even with extremely impaired kinase activity, still retains partial function in regulating plant growth and development, which raises the question of whether BRI1 kinase activity is essential for BR-mediated growth and development in higher plants.
文摘AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.
文摘Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spreading moxibustion group and a Western medicine group by the random number table method,with 30 cases in each group.The Western medicine group was treated with climen,starting from the 5th day of the menstrual cycle for 21 d.The spreading moxibustion group was treated with herb-partitioned spreading moxibustion at Baliao points on the basis of the medication in the Western medicine group,1 h per time,once a week.The treatment was performed for 1 month as one treatment course in both groups,for 3 courses in total.The serum follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)in the patients were measured before and after treatment.The peak systolic velocity(PSV)and resistance index(RI)were also detected.The traditional Chinese medicine(TCM)symptom score was evaluated.The clinical efficacy was evaluated after treatment.Results:The total effective rate in the spreading moxibustion group was 93.3%,which was significantly higher than 80.0%in the Western medicine group,and the difference between the groups was statistically significant(P<0.05).After treatment,the TCM symptom scores,the serum FSH levels,FSH/LH ratios and RI in both groups decreased,and the intra-group differences were all statistically significant(all P<0.05).The serum E2 level and PSV increased compared with those in the same group before treatment,and the intra-group differences were statistically significant(all P<0.05).After treatment,the TCM symptom score,the serum FSH level,FSH/LH ratio and RI in the spreading moxibustion group were lower than those in the Western medicine group,while the serum E2 level and PSV were higher than those in the Western medicine group,and the differences between the groups were statistically significant(all P<0.05).Conclusion:Herb-partitioned spreading moxibustion at Baliao points plus climen can produce valid therapeutic efficacy for DOR.It can improve the clinical symptoms,regulate serum hormone levels and increase ovarian blood perfusion,thus improving ovarian reserve function,producing more significant efficacy than climen alone.