A rare pediatric case of McCune–Albright syndrome with acute visual disturbance: Case report

Rationale:McCune–Albright syndrome (MAS) is a rare disorder characterized by clinical findings, which includes fibrous dysplasia (FD). FD is a benign tumor that leads to increased rates of bone fracture. In some MAS cases with FD, facial deformities, severe pain, and orbital neuropathies are complicated. Aneurysmal bone cyst (ABC) is a benign bone tumor and rare complication of FD.Patient concerns:A 9-year-old boy was admitted to our hospital because of acute visual disturbance.Diagnosis and interventions:The patient was clinically diagnosed as ABC complicated with MAS, and he underwent surgery.Outcomes:After the surgery, his sight became normal. Recurrence of ABC and visual disturbance was not observed in 3 years. Genetic analysis of a tissue sample from the ABC lesion by next-generation sequencing revealed a somatic activating GNAS mutation.Lessons:To the best of our knowledge, this is the first case report of MAS causing optic neuropathy complicated with ABC. ABC complicated with MAS is extremely rare, but it should be considered as a possible diagnosis in patients with acute visual loss and facial swelling. In addition, our case had OAS, which is an uncommon syndrome and a rare complication in ABC with MAS, and rapid decompression of the ABC was effective in improving the patient''s eyesight.     

Colonic Adenocarcinoma Metastatic to the Thyroid: Report of a Case

We report herein the case of a 67-year-old man who was admitted to our hospital with a 3-month history of hoarseness, a cervical mass, and weak muscles of the extremities 6 years after undergoing a right colectomy for carcinoma. Physical and imaging examinations disclosed a nodule in the thyroid with swollen cervical lymph nodes, multiple pulmonary lesions with pleural effusion, and a cerebral mass. Fine-needle aspiration cytology of the thyroid nodule and brush cytology of the lung mass revealed adenocarcinoma, which was consistent with a diagnosis of metastases from the primary colon adenocarcinoma to the thyroid, brain, and lung. The patient eventually died from the malignancy, although he survived for 4 months after the disclosure of the metastases. The rarity, diagnosis, and prognosis of thyroid metastasis from colon carcinoma are discussed. Received: February 22, 2001 / Accepted: July 17, 2001     

Sensitivity to GABA of neurons of the dorsal and ventral lateral geniculate nuclei in the rat

GABA was applied iontophoretically to dorsal and ventral lateral geniculate (LGd and LGv) neurons in rats. Spontaneous discharges were readily suppressed in both species of neurons. While in LGd neurons, evoked discharges by optic nerve stimulation were suppressed as readily as were spontaneous discharges, LGv neurons were characterized in that evoked discharges were much more resistant than spontaneous discharges.     

Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia

Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.     

Synergy of histone-derived peptides of coho salmon with lysozyme and flounder pleurocidin

Recent research has identified endogenous cationic antimicrobial peptides as important factors in the innate immunity of many organisms, including fish. It is known that antimicrobial activity, as well as lysozyme activity, can be induced in coho salmon (Oncorhynchus kisutch) mucus after exposure of the fish to infectious agents. Since lysozyme alone does not have antimicrobial activity against Vibrio anguillarum and Aeromonas salmonicida, a four-step protein purification protocol was used to isolate and identify antibacterial fractions from bacterially challenged coho salmon mucus and blood. The purification consisted of extraction with hot acetic acid, extraction and concentration on a C(18) cartridge, gel filtration, and reverse-phase chromatography on a C(18) column. N-terminal amino acid sequence analyses revealed that both the blood and the mucus antimicrobial fractions demonstrated identity with the N terminus of trout H1 histone. Mass spectroscopic analysis indicated the presence of the entire histone, as well as fragments thereof, including a 26-amino-acid N-terminal segment. These fractions inhibited the growth of antibiotic-supersuscptible Salmonella enterica serovar Typhimurium, as well as A. salmonicida and V. anguillarum. Synthetic peptides identical to the N-terminally acetylated or C-terminally amidated 26-amino-acid fragment were inactive in antimicrobial assays, but they potentiated the antimicrobial activities of the flounder peptide pleurocidin, lysozyme, and crude lysozyme-containing extracts from coho salmon. The peptides bound specifically to anionic lipid monolayers. However, synergy with pleurocidin did not appear to occur at the cell membrane level. The synergistic activities of inducible histone peptides indicate that they play an important role in the first line of salmon defenses against infectious pathogens and that while some histone fragments may have direct antimicrobial effects, others improve existing defenses.     

Neuronal protein NP25 interacts with F-actin

Neuronal protein NP25 is a neuron-specific protein present in highly differentiated neural cells, but its functional properties have not been well characterized. NP25 shows high amino acid sequence homology with the smooth muscle cell cytoskeleton-associated proteins, SM22, mp20, and calponin. To gain an insight into the biological functions of NP25, we first examined its subcellular localization in the human neuroblastoma cell line, SK-N-SH. NP25 diffusely distributed in the cytoplasm and fiber-like staining was also observed. It showed that NP25 co-localized with F-actin on stress fibers. A co-sedimentation assay demonstrated that NP25 bound to filamentous actin. Further investigations using fluorescence resonance energy transfer (FRET) technique revealed intracellular binding of NP25 and actin. The significance of the interaction between NP25 and F-actin is discussed.     

Computer-Aided Diagnosis for Detection of Lacunar Infarcts on MR Images: ROC Analysis of Radiologists’ Performance

The purpose of this study was to retrospectively evaluate radiologist performance in detection of lacunar infarcts on T1- and T2-weighted images, without and with the use of a computer-aided diagnosis (CAD) scheme. Thirty T1-weighted and 30 T2-weighted MR images obtained from 30 patients were used for assessing observer performance. These images were acquired using the fast spin-echo sequence with a 1.5-T MR imaging scanner. The group included 15 patients (age range, 48-83 years; mean age, 67.2 years; 10 men and five women) with a lacunar infarct and 15 patients (age range, 39-76 years; mean age, 64.0 years; eight men and seven women) without lacunar infarcts. Nine radiologists participated in the study. The radiologists initially interpreted the T1- and T2-weighted images without and then with the use of CAD, which indicated their confidence levels regarding the presence (or absence) of lacunar infarcts and the most likely position of a lesion on each MR scan. The observers' performance without and with the computer output was evaluated by performing receiver operating characteristic analysis. For the nine radiologists, the mean area under the best-fit binormal receiver operating characteristic curve plotted for unit square values of radiologists who interpreted the images without and with the scheme were 0.891 and 0.937, respectively. The performance of the radiologists improved significantly when they used the computer output (p=0.032). The CAD scheme has potential to improve the accuracy of radiologists' performance in detection of lacunar infarcts.     

Molecular evidence for multicentric development of thyroid carcinomas in patients with familial adenomatous polyposis

Familial adenomatous polyposis is characterized by multiple colorectal adenomas and an increased incidence of colorectal carcinomas. Patients also develop various extracolonic tumors, of which, thyroid carcinoma is common in young females. The occurrence of multiple carcinomas in one thyroid is frequently observed, although some carcinomas are solitary. To clarify whether each carcinoma develops independently or metastatically spreads from the first one formed, we analyzed the adenomatous polyposis coli (APC) gene mutation in each carcinoma. We found that each carcinoma had a different somatic mutation of the APC gene. This is molecular confirmation for the multicentric development of thyroid carcinomas in familial adenomatous polyposis through biallelic inactivation of the APC gene.     

Histochemical study of apoptosis and cell proliferation in hereditary intestinal diseases

The occurrence of apoptosis and cell proliferation in hereditary intestinal diseases was analyzed for possible diagnostic markers that could discriminate the formation of tumors that would develope into cancer. In all, 15 adenomas in familial adenomatous polyposis, 3 juvenile polyposis, 5 Peutz-Jeghers syndrome, 14 sporadic adenomas, and 46 colorectal carcinomas were investigated. Tissue specimens were examined for apoptotic cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and proliferating cells by immunohistochemistry of proliferating cells nuclear antigen (PCNA). In hereditary intestinal diseases, the apoptotic and proliferating indexes were significantly lower than those in colorectal carcinoma, and higher apoptotic and proliferating indexes were observed in poorly differentiated colorectal adenocarcinoma and in subserosal stages of invasion. There were no significant differences in proliferating and apoptotic indexes between adenoma in FAP and sporadic adenoma. No apoptotic and proliferating cells were observed in juvenile polyposis, and only occasional proliferating cells were seen in Peutz-Jeghers syndrome. These findings demonstrated that TUNEL and PCNA staining are useful in correctly reflecting disease progression in hereditary intestinal diseases.