Involvement of both protein kinase C and G proteins in superoxide production after IgE triggering in guinea pig eosinophils

ABSTRACTTo study the function and mechanism of eosinophils via the low affinity IgE receptor (FceRII), we examined the production of 02 metabolites by measuring the luminol-dependent chemiluminescence (LDCL) response and the generation of cysteinyl leukotrienes. Eosinophils obtained from guinea pig peritoneal fluid sensitized with horse serum were purified. Luminol-dependent chemiluminescence was induced by stimulation with monoclonal anti-CD23 antibody, but not by mouse serum (controls). The mean (±SEM) value of LDCL was 20.6±1.3X103 c.p.m. This reaction consisted of an initial rapid phase and a propagation phase and ended within lOmin. Guinea pig eosinophils were histochemically stained with monoclonal anti-CD23 antibody. The major product generated in the LDCL response was superoxide, as determined by the measurement of superoxide by cytochrome c reduction and the complete inhibitory effect of superoxide dismutase on the LDCL response. Pretreatment with either pertussis toxin or cholera toxin inhibited the LDCL reaction. Depletion of bivalent ions by EDTA inhibited this response and the protein kinase C inhibitor D-sphingosin inhibited both 1-oleoyl-2-acetyl-glycerol-induced and FcϵRII-mediated LDCL. These findings suggest that the NADPH-protein kinase C pathway may be involved in the FceRII-mediated LDCL response in guinea pig eosinophils

神経性食欲不振症に誤診された視床下部腫瘍の男性例

20歳の男性で,食欲不振,体重減少,自己嘔吐などの行動異常,病識のなさ,精神症状および人格の変化から最初の医療機関で神経性食欲不振症と誤って診断された.その後,複数の医療機関を受診したが,本人の精神および行動異常から十分な内科的検査がされず,全身状態の悪化と意識障害で当科に緊急入院した.胚細胞腫と考えられる視床下部腫瘍で,それによる下垂体機能低下症と尿崩症と診断された.患者は多飲多尿を申告せず,副腎皮質ホルモンの低下によって経過中に多尿は改善していたことが判明し,視床下部腫瘍による口渇感の喪失が明らかになった.Chipkevitchによる今まで報告された神経性食欲不振症に酷似した視床下部腫瘍21例の再検討では,やせをきたす身体疾患がないという項目以外の診断基準を完全に満たすものは2例であったが,行動および人格異常は,視床下部腫瘍による神経症状の出現に平均2.9年先行して出現しており,注意深い経過観察が必要なことを報告している.神経性食欲不振症患者数は増加しており,女子高校生や大学生の1%と推測されている.男性例も稀ではなくなり,全患者の1～5%で,当科でも1.3%である.しかし,本症の診断には器質的疾患の鑑別は非常に重要である.下垂体機能低下症と異なり,神経性食欲不振症では,血漿成長ホルモン,ACTH,コルチゾールが高値となることが多く,鑑別に有用である.A 20-year-old Japanese man with a hypothalamic tumor which caused hypopituitarism and diabetes insipidus was mistakenly diagnosed as anorexia nervosa because of anorexia, weight loss, denial of being ill, changes in personality, and abnormal behavior resembling the clinical characteristics of anorexia nervosa. After irradiation therapy, he gained weight and is behaving normally under replacement therapy. Unlike in hypopituitarism, anorexia nervosa patients often have elevated plasma levels of growth hormone (GH), cortisol or adrenocorticotropin (ACTH). Careful testing and examination must be performed to distinguish between anorexia nervosa and other organic disorders

神経性食欲不振症に誤診された視床下部腫瘍の男性例

20歳の男性で,食欲不振,体重減少,自己嘔吐などの行動異常,病識のなさ,精神症状および人格の変化から最初の医療機関で神経性食欲不振症と誤って診断された.その後,複数の医療機関を受診したが,本人の精神および行動異常から十分な内科的検査がされず,全身状態の悪化と意識障害で当科に緊急入院した.胚細胞腫と考えられる視床下部腫瘍で,それによる下垂体機能低下症と尿崩症と診断された.患者は多飲多尿を申告せず,副腎皮質ホルモンの低下によって経過中に多尿は改善していたことが判明し,視床下部腫瘍による口渇感の喪失が明らかになった.Chipkevitchによる今まで報告された神経性食欲不振症に酷似した視床下部腫瘍21例の再検討では,やせをきたす身体疾患がないという項目以外の診断基準を完全に満たすものは2例であったが,行動および人格異常は,視床下部腫瘍による神経症状の出現に平均2.9年先行して出現しており,注意深い経過観察が必要なことを報告している.神経性食欲不振症患者数は増加しており,女子高校生や大学生の1%と推測されている.男性例も稀ではなくなり,全患者の1～5%で,当科でも1.3%である.しかし,本症の診断には器質的疾患の鑑別は非常に重要である.下垂体機能低下症と異なり,神経性食欲不振症では,血漿成長ホルモン,ACTH,コルチゾールが高値となることが多く,鑑別に有用である.A 20-year-old Japanese man with a hypothalamic tumor which caused hypopituitarism and diabetes insipidus was mistakenly diagnosed as anorexia nervosa because of anorexia, weight loss, denial of being ill, changes in personality, and abnormal behavior resembling the clinical characteristics of anorexia nervosa. After irradiation therapy, he gained weight and is behaving normally under replacement therapy. Unlike in hypopituitarism, anorexia nervosa patients often have elevated plasma levels of growth hormone (GH), cortisol or adrenocorticotropin (ACTH). Careful testing and examination must be performed to distinguish between anorexia nervosa and other organic disorders

Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity

Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake. GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary. Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach. Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown. We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. Tg rats had lower body weight and less adipose tissue than did control rats. Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats. GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats. These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity