ABSTRACT
Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Abeta). Abeta, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca(2+) homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without Abeta and isolated a Ca(2+)-dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with Abeta. We focused on annexin A5, among these proteins, because it binds both Ca(2+) and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (P < 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD.
Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/diagnosis , Annexin A5/biosynthesis , Cerebral Cortex/metabolism , Disease Models, Animal , Neurons/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/biosynthesis , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/physiology , Animals , Annexin A5/blood , Biomarkers/blood , Calcium Signaling/physiology , Cell Culture Techniques/methods , Cells, Cultured , Cerebral Cortex/pathology , Female , Gene Expression Regulation/physiology , Homeostasis/genetics , Homeostasis/physiology , Humans , Male , Mice , Mice, Inbred ICR , Mice, Transgenic , Neurons/cytology , Neurons/pathology , Organ Specificity/genetics , Organ Specificity/physiologyABSTRACT
We examined the feasibility of sentinel lymph node biopsy for papillary thyroid cancer. In the dye injection method, 1% of isosulfan blue dye was injected around the tumor of 32 patients intra-operatively, and in the radioisotope (RI) colloid injection method, 99mTc-tin colloid was injected in 23 patients 1 day preoperatively. Lymph node mapping for detection of sentinel nodes was performed after thyroidectomy and central and modified lateral neck lymph node dissections. All dissected nodes were examined postoperatively by hematoxylineosin staining to determine whether or not metastasis was present. In the dye injection method, sentinel lymph nodes were identified in 30 (94%) of the 32 patients. Lymph node metastases were found in 14 patients, and some sentinel lymph nodes had papillary cancer metastasis in 13 patients. There was only 1 false-negative case. Sensitivity and accuracy of sentinel lymph node biopsy was 93% (13/14) and 97% (29/30). With the RI method, detection rate, sensitivity and accuracy of sentinel lymph node biopsy was 96% (22/23), 90% (9/10) and 95% (21/22), respectively. Our preliminary study indicated that sentinel lymph node biopsy was feasible in patients with thyroid cancer. It may be helpful in avoiding unnecessary lymph node dissection and improving quality of life in patients with thyroid cancer.
Subject(s)
Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy , Humans , Lymph Node Excision , Lymphatic Metastasis , Radiopharmaceuticals , Risk Assessment , Rosaniline Dyes , Sensitivity and Specificity , Technetium Tc 99m Sulfur Colloid , Treatment OutcomeABSTRACT
Recent studies have shown that the prognosis of patients with multicentric occurrence (MO) of hepatocellullar carcinoma (HCC) after curative resection, whether synchronous or metachronous, is significantly better than that of patients with intrahepatic metastasis (IM). We attempted to elucidate a group with high probability of MO of HCC by comparing the preoperative ultrasonography (US), computed tomography during arterial portography (CTAP) and CT arteriography (CTA) images with the histological grading of the non-cancerous region of the liver. The imaging and pathological characteristics of 97 nodules in 45 patients diagnosed as having small (<5cm) and oligonodular HCCs preoperatively were investigated. Histological diagnoses were as follows: 18 MO, 23 IM, and 4 unclassified (HCC with benign nodule). Histological grade of the liver tissue was assessed using the hepatitis activity index (HAI) score. No significant differences in tumor location and the mean size of co- or daughter nodules were noticed between the MO and IM patients. Of the 38 nodules in the MO patients, 20 were diagnosed as hyperechoic lesions on US, 20 as negative enhanced lesions on CTA and 12 as having positive portal flow on CTAP. A comparison of image-patterns between the synchronous nodules revealed that the MO group showed different images in at least one imaging technique, whereas in most IM patients similar images were produced by two or three imaging techniques. Moreover, all MO patients had an [Formula: see text], although more than half the IM patients had an [Formula: see text]. In patients with small and oligonodular HCCs, the nodules are highly likely to display MO, when showing both 1 or more different image patterns among US, CTA and CTAP and severe hepatitis such as HAI score >/=8.
