No abstract available.
Epidemiologic Studies* ; Humans ; Infant, Newborn*

beta-amyloid peptide (Abeta) consisting of 40 to 42 amino acid is the principle constituent of senile plaques in Alzheimer's disease. Although, the hypothesis that deposition of AP triggers a cascade of events leading to the pathology of Alzheimer's disease has been widely accepted, direct evidence for triggering accumulation of phosphorylated tau in paired helical filament is rare. In this study, we examined neurotoxicity induced by 3 kinds of beta-amyloid peptides 1 ~28, 25~,35 and 1~40 to elucidate the way of mechanism trading to neuronal cell death caused by Abeta using cultured hippocampal neurons. For this purpose, we measured lactate dehydrogenase (LDH) in the culture media after treatment with Abeta combined with anti-oxidant drug, trolox, or not. By histochemical and TUNEL method, we studied the change of immunoreaction to anti-MAP-2 (microtubule associated protein -2, the main component of neuritis) and detected apoptotic cells, respectively, in the hippocampal neurons treated with Abeta. To investigate whether tau phosphorylation involve neurotoxicity induced by Abeta, we immunostained the neurons with anti-SMI-31 to recognize phosphorylated Ser 396/404 of tau. From our data, we suggested that Abeta1-40 and Abeta25-35 induced marked neurodegenerative changes, and the mechanism responsible for cell death caused by Abeta -neurotoxicity was associated with the apoptosis. Because Abeta-neurotoxicity was not inhibited by anti-oxidant, trolox, we suggested that anti-oxidant did not protect the neuronal cells against the damage induced by Abeta in ou. expo.imental envi.onment. Finally, we suggested that AP treatment did not potentiate the immunoreactivity to anti-phosphorylated tau antibody and we speculated that Abeta-neurotoxicity led hippocampal cells to apoptosis without tau phosphorylation.
Alzheimer Disease ; Apoptosis* ; Cell Death ; Culture Media ; In Situ Nick-End Labeling ; L-Lactate Dehydrogenase ; Neurons* ; Pathology ; Peptides* ; Phosphorylation* ; Plaque, Amyloid

Translocation of synaptic zinc may mediate neuronal death in pathological conditions. In this study, we examined the possible correlation between zinc translocation and heat shock protein (HSP)72 induction in rat brains following kainate seizures. Zinc accumulation, visualized by Timm's method, occurred in degenerating neurons in hippocampus, amygdala, and cortex 6~24 h after kainate injection. Immunohistochemistry with anti-HSP72 antibody revealed HSP induction largely in areas where zinc accumulation occurred. At the cellular level, however, most HSP72 immunoreac-tive neurons were found to be Timm (-) and morphologically intact. Present results suggest that intense zinc translocation may induce neuronal death before possible HSP induction. However, we could not rule out the possibility that sublethal zinc translocation, below the detection limit by Timm's method, may play a role in HSP72 induction.
Amygdala ; Animals ; Brain* ; Heat-Shock Proteins* ; Hippocampus ; Hot Temperature* ; Immunohistochemistry ; Kainic Acid* ; Limit of Detection ; Neurons ; Rats* ; Seizures* ; Zinc*

OBJECTIVE: Gastric carcinoma is one of the most common cause of death in Korea with limited effectiveness of chemotherapy. Thymidylate synthase(TS) is a critical therapeutic target for the fluoropyrimidine cytotoxic drugs, that are the mainstay of the treatment for the advanced gastrointestinal malignancies. We assessed the relationship between the levels of TS expression and survival and effect of 5-fluorouracil based chemotherapy in gastric adenocarcinoma. METHODS: Thirty six patients with gastric adenocarcinoma who underwent curative resection of stomach at Ewha Womans University Hospital were evaluated. TS protein expression in tumor tissues was assessed by standard immunohistochemical staining techniques with TS 106 monoclonal antibody. RESULTS: TS expression was high(3+) in 19 patients (52.8%) and low(< or =2+) in 17 patients(47.2%). Between these two groups, there was no significant difference in the histopathologic type or stage. Seventy-two point five percent of patients with low TS expression were disease free at 5 years compared with 58.2% of patients with high TS expression(p=0.31) and 73.7% of patients with low TS expression were alive at 5 years compared with 61.4% of patients with high TS expression(p=0.34). In patients with high TS expression, disease-free survival (DFS) and overall survival(OS) of patients who received adjuvant chemotherapy were longer than those of patients with surgery alone without significance(p=0.28, p=0.16). CONCLUSIONS: We could not confirm the association between the level of TS expression in tumor tissues and DFS and OS of patients with gastric adenocarcinoma who underwent curative resection. Further study with more cases as well as prospective study will be necessary for establishment of relationship between TS expression of tumor and prognosis of gastric adenocarcinoma
Adenocarcinoma* ; Cause of Death ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Female ; Fluorouracil ; Humans ; Korea ; Prognosis* ; Stomach ; Thymidylate Synthase*

Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of TNF-alpha and reduced the protein and mRNA expression of TNF-alpha in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-alpha and the expressions of scavenger receptors.
Animals ; Cytokines ; Diet, High-Fat ; Dinoprostone ; Down-Regulation ; Hand ; Inflammation ; Insulin Resistance ; Interleukin-10 ; Interleukin-4 ; Interleukin-6 ; Macrophages ; Macrophages, Peritoneal ; Metformin ; Mice ; Mice, Obese ; NF-kappa B ; Obesity ; Prevalence ; Receptors, Scavenger ; RNA, Messenger ; Tumor Necrosis Factor-alpha

Nitric oxide (NO) is a short lived membrane permeable gas, a recently identified neuronal messenger molecule, and implicated in several activity-dependent forms of synaptic plasticity. The histochemical staining of NADPH-diaphorase (NADPH-d) provides a simple method to select populations of neurons containing nitric oxide synthase (NOS), throughout the brain. The NADPH-d positive neurons, uniquely resistant to toxic insults and neurodegenerative diseases, have been colocalized with neurons in the brain and peripheral tissue containing NOS. Apodemus agrarius has been used for experimental purpose to identify the route of infection and pathogenesis of korean hemorrhagic fever. However, despite of the increasing publication at present about the physiologic and ecologic characteristics of Apodemus, a few data are available about the morphologic findings in the brain. In this study we used NADPH-d histochemistry to evaluate the distribution of neurons, contain NOS, on the postnatal development in cerebral cortex and striatum of the Apodemus agrarius. In the cerebral cortex of Apodemus agrarius, NADPH-d positive neurons were observed in all cortical layers, but were concentrated in V-VI layer. NADPH-d positive neurons of forebrain were more dense than other cortical regions. At 1 week after birth, NADPH-d positive neurons had short processes and immature features. In contrast, at 12 weeks after birth, NADPH-d positive neurons had longer and more complex processes than that of earlier ages. In the striatum, NADPH-d positive neurons were intensely stained, predominantly medium-sized neurons. They had multipolar or bipolar dendritic branches which belong to fusiform or stellate cell types in all groups. In addition, at 4 and 12 weeks after birth, NADPH-d positive neurons had long and complex fiber network. The number of NADPH-d positive neurons in the striatum was relatively decreased during postnatal development. However, the length and complexity of their processes were relatively increased after birth. Present results showed postnatal maturation patterns such as morphological features of NADPH-d positive neurons. These findings suggest that NADPH-d positive neurons will be reach adult level after 4 weeks of postnatal age. Therefore, this report provide the morphological evidence supporting the hypothesis that NO may be play a role in regulation of neuronal development and synaptic plasticity during postnatal development of Apodemus agrarius.
Adult ; Animals ; Brain ; Cerebral Cortex* ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Membranes ; Murinae* ; Neurodegenerative Diseases ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase ; Parturition ; Plastics ; Prosencephalon ; Publications

It has been estimated that chromosomal aberrations account for 2.3% to 3% of normal pregnancies, and of them, 85% are aborted. Therefore, the survival rate of neonates with chromosomal aberrations is very low. Among them, patients with partial deletion of the long arm of chromosome 13 are very rare. The natural history of deletion of the long arm is dependent on the deleted segment. It has been known that patients with proximal deletions not extending into q32 usually show mild to moderate mental retardation, variable minor anomalies, and growth retardation. Patients with more distal deletions, including at least part of q32, usually have severe mental retardation, growth deficiency, and major malformations including microcephaly and CNS defects, distal limb anomalies, eye defects, and gastrointestinal malformation. We report a case of a 13(q24) deletion male infant who showed intrauterine growth retardation, imperforate anus, CNS anomalies, hydronephrosis, clubfoot, clinodactyly and developmental delay, although his deletion site was proximal to q32.
Anus, Imperforate ; Arm ; Chromosome Aberrations ; Chromosome Disorders ; Chromosomes, Human, Pair 13 ; Clubfoot ; Extremities ; Fetal Growth Retardation ; Humans ; Hydronephrosis ; Infant ; Infant, Newborn ; Intellectual Disability ; Male ; Microcephaly ; Natural History ; Pregnancy ; Survival Rate

Orbital complications after endoscopic sinus surgery (ESS), such as optic nerve or medial rectus injuries, are well known, but isolated complete oculomotor nerve palsy has never been reported. In this case, a 31-year-old male was transferred to our hospital after ESS. Physical examination showed complete left oculomotor nerve palsy, with a bony defect on the sellar floor, which had not fully recovered after more than 1 year. We hypothesized that blunt trauma could be the main cause of the oculomotor palsy. Surgeons performing ESS must keep in mind the possibility of oculomotor palsy due to blunt trauma, especially when operating around the sphenoid and posterior ethmoid sinus.
Adult ; Ethmoid Sinus ; Ethmoid Sinusitis ; Fistula* ; Humans ; Male ; Oculomotor Nerve Diseases ; Optic Nerve ; Orbit ; Paralysis ; Physical Examination

It has been reported that injection of Freund's complete adjuvant (FCA) into the hindpaw of a rat induces inflammatory responses with accompanying pain behaviors. Signs of pain behaviors observed in FCA-injected animals were reported to be similar to symptoms seen in patients with inflammatory pain. The nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) is a selective histochemical marker for the nitric oxide synthesizing enzyme, nitric oxide synthase (NOS). N (G)-nitro-L-arginine methyl ester (L-NAME) is a NOS inhibitor. In the present study, we examined if inflammaory pain causes increases in NADPH-diaphorase reactivities in neurons of the dorsal root ganglia (DRG). The results were as follows; 1. FCA-induced inflammation on a limb increased staining density (SD) of NADPH-d positive neurons in the ipsilateral side DRG. 2. Pretreatment of L-NAME did not changed SD of NADPH-d positive neurons on the inflammation of contralateral side DRG 3. Posttreatment of L-NAME decreased the inflammation induced SD of NADPH-d positive neurons. 4. n-NOS immunoreactivity did not match NADPH-d histochemical study, implying the constant level of enzyme itself. Inflammation pain on a hindlimb increased staining density of NADPH-diaphorase positive neuron in the DRG, which was decreased by L-NAME. L-NAME also decreased pain perception. This suggests a role of NO in the pain perception and/or modulation at the level of DRG.
Animals ; Diagnosis-Related Groups* ; Extremities ; Ganglia, Spinal ; Hindlimb ; Humans ; Inflammation ; NAD ; NADP ; Neurons ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Nitric Oxide* ; Pain Perception ; Rats*

BACKGROUND: Most of adult patients with chronic immune thrombocytopenic purpura (ITP) that was refractory or relapsed to high-dose corticosteroid have been treated with splenectomy as a 2nd line treatment. However, these patients may have increased morbidity and mortality according to the operation and the increased risk of infection for a lifetime after splenectomy. Despite of the above risks, 30~40% of these patients can't maintain remission. Furthermore, the remission rate after splenectomy is relatively lower in patients with corticosteroid-refractory chronic ITP than that in those patients with corticosteroid-responsiveness. We studied whether danazol, an attenuated androgen, is useful or safe as 2nd line treatment for chronic ITP instead of splenectomy and which factors are associated with the response to danazol. METHODS: Among the patients with chronic ITP who failed corticosteroid therapy in our hospital, 28 patients who received danazol as the 2nd line treatment were analyzed retrospectively. A complete response was defined that the platelet count was increased to 150 x 10(3)/microL, and a partial response was defined that the platelet count was increased above 50 x 10(3)/microL or there was an increased platelet count of more than 20 x 10(3)/microL from the pre-treatment platelet count when the platelet count was above 50 x 10(3)/microL at the time of danazol therapy. RESULTS: The median age of patients was 44 years (range: 19~67) and the number of male patients was 9 (32.1%) and the number of females was 19 (67.9%). The starting daily doses of danazol were variable from 200 to 600mg, though most of the patients were treated with 400mg daily (18 cases, 64.3%). The median duration of danazol therapy was 201.5 days (range: 13~973) and the median duration from ITP diagnosis to danazol treatment was 56 days (range: 20~2,430). Among the accrued 28 patients, 22 patients showed a response to danazol (78.5%); there were 6 patients (21.4%) with a complete response and 16 patients (57.1%) with a partial response. The median duration from danazol treatment to response was 30 days (range: 0~180). The median response duration of danazol treatment was 330 days (95% CI: 182~478) by the Kaplan-Meiyer method. For the danazol-responsive patients, 9 patients (40.9%) remained in remission and 13 patients (59.1%) relapsed. Grade 3~4 toxicity was observed in two patients and three patients stopped danazol because of adverse effects. Hepatotoxicity was the most common toxicity. CONCLUSION: Our findings suggest that danazol is a beneficial, safe choice as the 2nd line treatment for patients with chronic ITP that was refractory or relapsed to corticosteroid.
Adult ; Danazol* ; Diagnosis ; Female ; Humans ; Male ; Mortality ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Splenectomy