A case of allergic bronchopulmonary mycosis due to Schizophyllum commune with elevated serum carcinoembryonic antigen levels.

A 78-year-old Japanese woman without any history of asthma or smoking presented prolonged cough. Laboratory data showed elevated serum CEA levels and a chest CT revealed a mass with abnormal uptake in the left lower lobe. One month later, the mass spontaneously regressed, and CEA levels improved. However, the symptoms progressed during the observation period without treatment. Chest radiograph findings revealed collapse of the right middle lobe, and Schizophyllum commune was isolated from the mucous plugs; the patient was diagnosed with allergic bronchopulmonary mycosis (ABPM). Herein, we report the first case of ABPM caused by S. commune with elevated CEA levels and mimicking lung cancer.

Role of Insulin-like Growth Factor-1 in the Central Regulation of Feeding Behavior in Chicks.

Insulin-like growth factor-1 (IGF-1) is a key regulator of muscle development and metabolism in chickens. Recently, we have demonstrated that intracerebroventricular administration of IGF-1 significantly decreased food intake in broiler chicks. However, the molecular mechanisms underlying the IGF-1-induced anorexia and the anorexigenic effect of IGF-1 in different strains of commercial chicks have not been investigated. Neuropeptide Y (NPY, a hypothalamic orexigenic neuropeptide), agouti-related protein (AgRP, a hypothalamic orexigenic neuropeptide), and proopiomelanocortin (POMC, the precursor of hypothalamic anorexigenic neuropeptides) play important roles in the regulation of food intake in both mammals and chickens. Evidence shows that several cell signaling pathways in the hypothalamus are involved in regulating the feeding behavior of mammals. In the present study, we first investigated the effects of IGF-1 on the expression of appetite-regulating neuropeptides and phosphorylation of signaling molecules in the hypothalamus of broiler chicks. Intracerebroventricular administration of IGF-1 significantly increased the mRNA levels of POMC, whereas the mRNA levels of NPY and AgRP were not significantly altered. IGF-1 also significantly induced the phosphorylation of v-Akt murine thymoma viral oncogene homolog 1 (AKT) in the hypothalamus of chicks, but did not influence the phosphorylation of forkhead box O1, S6 protein, AMP-activated protein kinase, and extracellular signal-regulated kinase 1/2. We also compared the effect of IGF-1 on food intake in broiler chicks (a hyperphagic strain of chickens) and layer chicks. Results demonstrated that the threshold of IGF-1-induced anorexia in broiler chicks was higher than that in layer chicks. Our observations suggest that hypothalamic POMC and AKT may be involved in the IGF-1-induced anorexigenic pathway and that high threshold of IGF-1-induced anorexia in broiler chicks might be one of the causes of hyperphagia in broiler chicks. Overall, it appears that IGF-1 plays important roles in the central regulation of feeding behavior in chicks.

Effects of Fasting and Refeeding on the mRNA levels of Insulin-like Growth Factor-binding Proteins in Chick Liver and Brain.

The physiological functions of insulin-like growth factor-binding proteins (IGFBPs) in mammals have been evaluated in several studies. However, the physiological roles of IGFBPs in chickens have not yet been elucidated. In this study, we examined the effects of short-term (6 h) fasting and refeeding on the mRNA levels of IGFBPs in chick liver and brain. Eighteen 8-day-old chicks were weighed and allocated to three groups on the basis of body weight, and subjected to ad libitum feeding, 6 h of fasting, or 6 h of fasting followed by 6 h of refeeding. After the chicks were euthanized by decapitation, the liver and brain were excised, and the brain was dissected into six segments (telencephalon, optic lobes, cerebellum, rostral part of the brainstem, middle part of the brainstem, and caudal part of the brainstem). IGFBP mRNA levels were determined by qRT-PCR. Fasting significantly increased the mRNA levels of IGFBP-1 and -2 in the chick liver, and these changes were reversed by 6 h of refeeding. The mRNA levels of IGFBP-3 in the middle part of the brainstem and IGFBP-5 in the optic lobes were decreased by 6 h of fasting and were not reversed after 6 h of refeeding. These findings suggest that IGFBP-1 and -2 in the liver, IGFBP-3 in the middle part of the brainstem, and IGFBP-5 in the optic lobes may play physiological roles in response to short-term changes in the nutritional status of chicks.

Central and peripheral administrations of insulin-like growth factor-1 suppress food intake in chicks.

A number of studies have been made on the physiological actions of insulin-like growth factor-1 (IGF-1) in mammals and birds. In mammals, the effects of central administration of IGF-1 on food intake have been examined. For example, intracerebroventricular administration of IGF-1 significantly decreased food intake in diabetic rats, but not in sheep and nondiabetic rats. The chicken is known to be a hyperglycemic animal. Like satiety hormones, plasma IGF-1 levels are elevated postprandially in chickens. In this study, we hypothesized that IGF-1 is involved in the regulation of food intake in chickens. Intracerebroventricular administration of IGF-1 significantly suppressed food intake in chicks in a dose dependent manner. Both the mRNAs of IGF-1 and its receptor were expressed throughout the brain. However, the mRNA levels of IGF-1 were not influenced by fasting and refeeding in all regions of the brain. On the other hand, 6h of fasting significantly suppressed mRNA expression of hepatic IGF-1, and this effect was significantly reversed by 6h of refeeding. Furthermore, intravascular administration of IGF-1 significantly suppressed food intake in chicks. These findings suggest that IGF-1 may function as a satiety hormone in chickens.

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4(+) T Lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that favors the cerebrum and typically occurs in immunosuppressed patients. We herein report the case of a 66-year-old man with PML, idiopathic CD4(+) T lymphocytopenia (ICL), and chronic renal failure. Cranial magnetic resonance imaging (MRI) showed a crescent-shaped lesion in the left cerebellum, brainstem, and middle cerebellar peduncle. Although the patient did not present with HIV infection, collagen diseases, or tumors, JC virus DNA was detected in the cerebrospinal fluid. Clinicians should consider PML and ICL in the differential diagnosis if the patient develops progressive ataxia and a crescent-shaped cerebellar lesion on MRI.

Four-dimensional volume-rendered imaging of the fetal ventricular outflow tracts and great arteries using inversion mode for detection of congenital heart disease.

AIM: Using four-dimensional (4D) sonography with an inversion mode, we evaluated fetal ventricular outflow tracts and great vessels for the detection of congenital heart disease. METHODS: Volume datasets of the fetal heart were acquired with spatiotemporal image correlation (STIC), which uses automated transverse and longitudinal sweeps of the anterior chest wall. A total of 12 normal fetuses and seven fetuses with congenital heart disease (one case of double-outlet right ventricle, one case of tetralogy of Fallot, one case of transposition of the great arteries, one case of hypoplastic pulmonary artery with a large ventricular septal defect, and three cases of hypoplastic left heart syndrome) at 16-37 weeks of gestation were studied using transabdominal 4D sonography with an inversion mode. 4D inversion mode images of great arteries were evaluated. RESULTS: 4D ultrasound with an inversion mode demonstrated real-time 3D angiographic features of fetal cardiac outflow tracts in both normal and abnormal fetal hearts. This modality facilitated visualization of the relationships, size, and course of the outflow tracts, thus helping the examiner to more effectively understand the spatial relationships between the vessels. In normal fetal hearts, it was clearly shown that the pulmonary artery crosses in front of the aorta. In the three cases of hypoplastic left heart syndrome, an extremely small ascending aorta was evident. In the one case of tetralogy of Fallot, a relatively small pulmonary artery was noted. In the one case of hypoplastic pulmonary artery with a large ventricular septal defect, a markedly small main pulmonary artery was depicted. In the case of transposition of the great arteries, the vessels left the ventricles parallel to each other. In the case of double-outlet right ventricle, great arteries leaving the right ventricle in parallel were shown. CONCLUSION: 4D ultrasound in the inversion mode provides a means of evaluating fetal cardiac outflow tracts in 3D in real time. This technique may assist in the evaluation of spatial relationships between the great vessels and both ventricles, and the difference in the size of great vessels. Moreover, the inversion mode images should be more readily discernible than those obtained by conventional ultrasonography. 4D ultrasound in the inversion mode may be an important modality in future fetal cardiac research and in the evaluation of fetal congenital heart disease.

Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome.

Trisomy 21 or Down syndrome (DS) is the most common genetic birth defect associated with mental retardation. The over-expression of genes on chromosome 21, including SOD1 (Cu/Zn superoxide dismutase) and APP (amyloid-beta precursor protein) is believed to underlie the increased oxidative stress and neurodegeneration commonly described in DS. However, a segmental trisomy 16 mouse model for DS, Ts1Cje, has a subset of triplicated human chromosome 21 gene orthologs that exclude APP and SOD1. Here, we report that Ts1Cje brain shows decreases of mitochondrial membrane potential and ATP production, increases of reactive oxygen species, hyperphosphorylation of tau without NFT formation, increase of GSK3beta and JNK/SAPK activities and unaltered AbetaPP metabolism. Our findings suggest that genes on the trisomic Ts1Cje segment other than APP and SOD1 can cause oxidative stress, mitochondrial dysfunction and hyperphosphorylation of tau, all of which may play critical roles in the pathogenesis of mental retardation in DS.

Syntheses of vanadyl and zinc(II) complexes of 1-hydroxy-4,5,6-substituted 2(1H)-pyrimidinones and their insulin-mimetic activities.

Control of the glucose level in the blood plasma has been achieved in vitro and in vivo by administration of vanadium and zinc in form of inorganic salts. It has been shown that elements are poorly absorbed in their inorganic forms and required high doses which have been associated with undesirable side effects. Many researchers, therefore, have focused on metal complexes that were prepared from VOSO(4) or ZnSO(4) and low-molecular-weight bidentate ligands. Seven kinds of 1-hydroxy-4,6-disubstituted and 1-hydroxy-4,5,6-trisubstituted-2(1H)-pyrimidinones were synthesized by reaction of N-benzyloxyurea and beta-diketones and subsequent removal of the protecting group. Six kinds of 1-hydroxy-4-(substituted)amino-2(1H)-pyrimidinones were synthesized by the substitution reaction of 1-benzyloxy-4-(1',2',4'-triazol-1'-yl)-2(1H)-pyrimidinone with various alkyl amines or amino acids. Treatment with VOSO(4) and ZnSO(4) or Zn(OAc)(2) afforded vanadyl(IV) and zinc(II) complexes which were characterized by means of (1)H NMR, IR, EPR, and UV-vis spectroscopies, and combustion analysis. The in vitro insulin-mimetic activity of these complexes was evaluated from 50% inhibitory concentrations (IC(50)) on free fatty acid (FFA) release from isolated rat adipocytes treated with epinephrine. Vanadyl complexes of 4,6-disubstituted-2(1H)-pyrimidinones showed higher insulin-mimetic activities than those of 4,5,6-trisubstituted ones. On the other hand, Zn(II) complexes showed lower insulin-mimetic activities than VOSO(4) and ZnSO(4) as positive controls. It was found that the balance of the hydrophilicity and/or hydrophobicity is important for higher insulin-mimetic activity. The in vivo insulin-mimetic activity was evaluated with streptozotocin (STZ)-induced diabetic rats. Blood glucose levels were lowered from hyperglycemic to normal levels after the treatment with bis(1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato)oxovanadium(IV) by daily intraperitoneal injections. The improvement in glucose tolerance was also confirmed by an oral glucose tolerance test.

Decreased cell proliferation in the dentate gyrus of rats after repeated administration of cocaine.

Cell proliferation in the dentate gyrus of hippocampus was assessed using in vivo labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats that were administered cocaine (20 mg/kg) for 14 consecutive days. Rats showed increased stereotypy at a challenge dose of cocaine after 1 week of withdrawal, suggesting the acquisition of behavioral sensitization. Twenty-four hours after final injection of repetitive cocaine administration, a 26% decrease in BrdU-positive cells was observed, compared with control rats. However, this returned to control level within 1 week. No differences were observed in rats that received a single injection of cocaine. Differentiation of newly formed cells was not influenced. These data imply that the regulation of hippocampal cell proliferation by cocaine may be involved in the development of certain symptoms of addiction, such as cognitive impairment and acquisition of behavioral sensitization.

Laryngeal stridor in multiple system atrophy.

The purpose of this study was to elucidate the clinical features of laryngeal stridor in 104 patients with multiple system atrophy (MSA) and to predict the hazard risk. Stridor was observed in 36 patients. It occurred in the first year of the disease in 10 cases, and 69% of the cases were diagnosed with stridor within the first 4 years. Dysphagia and hoarseness had a statistically higher frequency in the stridor group, and the onset period of these elements correlated with the onset of stridor. A follow-up study of survival probability was carried out in 83 patients. The median survival period in the stridor group (33 cases) and the non-stridor group (50 cases) was 8.0 and 9.0 years, respectively. Treatment for stridor decreased the relative risk from 2.998 to 0.147. Laryngeal stridor is a common and early clinical symptom in MSA. Early treatment for stridor is advisable to reduce mortality.

Repeated cocaine administration differentially affects NMDA receptor subunit (NR1, NR2A-C) mRNAs in rat brain.

We investigated the effects of intermittent intraperitoneal (i.p.) injections of cocaine (20 mg/kg) on subunit mRNAs of N-methyl-D-aspartate (NMDA) receptors (NR1/NR2A-2C) in the rat brain by in situ hybridization using phosphor screen analysis. The level of NR1 subunit mRNA significantly increased in hippocampal complexes 1 h after a single i.p. injection of cocaine. After repeated cocaine injection, the mean scores of stereotyped behavior were increased with the number of injections. The level of NR1 subunit mRNA was obviously decreased in the striatum and cortices 24 h (early withdrawal) after a final injection following 14 days of subchronic administration. During the early withdrawal period, the amount of the NR1 subunit decreased in the nucleus accumbens, globus pallidus, and subiculum. In the dentate gyrus, the NR1 mRNA level significantly increased during early withdrawal in rats subchronically treated with cocaine. Levels of NR2B subunit mRNA were reduced in the cortices and striatum. During late withdrawal from cocaine, the level of NR2C subunit mRNA in the cerebellum was also reduced. These findings suggest that the disruption of NR1, NR2B, and NR2C subunits in the discrete brain regions occurs under the cocaine-related behavioral abnormalities and would be closely implicated in the initiation and expression of behavioral sensitization induced by repeated cocaine administration. Further studies on the changes in non-NMDA receptors are required to elucidate the biological significance of glutamate receptors for the mechanisms underlying the development of behavioral sensitization.

Repeated cocaine administration increases GABA(B(1)) subunit mRNA in rat brain.

The effects of a single and repeated administration of cocaine on GABA(B) receptor subunit mRNA was investigated in rat brain by in situ hybridization. Following a single administration of cocaine, no significant change was observed in any brain regions examined, neither 1 h nor 24 h after administration. During repeated administration of cocaine, behavioral sensitization with increased stereotyped behavior was observed. A significant increase in the level of GABA(B(1)) mRNA was observed in the nucleus accumbens (11.4%), CA1 field of the hippocampus (16.8%), and thalamus (16.5%) 1 day after repeated administrations of cocaine for 14 consecutive days. The level of mRNA returned to the basal level 1 week after the final injection of repeated cocaine treatment. The observed changes in the mRNA level after the repeated cocaine may imply changes of GABA(B(1)) subunit in molecular mechanisms which underlie development of behavioral sensitization.