Wall Enhancement of the Intracranial Aneurysms Revealed by Magnetic Resonance Vessel Wall Imaging Using Three-Dimensional Turbo Spin-Echo Sequence with Motion-Sensitized Driven-Equilibrium: A Sign of Ruptured Aneurysm?

PURPOSE: Wall enhancement of saccular cerebral aneurysms has not been researched sufficiently. Our purpose of this study was to investigate the incidence of aneurysmal wall enhancement by the three-dimensional turbo spin-echo sequence with motion-sensitized driven equilibrium (MSDE-3D-TSE) imaging after gadolinium injection. METHODS: We retrospectively reviewed the pre- and postcontrast MSDE-3D-TSE images of 117 consecutive patients with intracranial aneurysms from September 2011 to July 2013. A total of 61 ruptured and 83 unruptured aneurysms of 61 patients with subarachnoid hemorrhage (SAH) and 56 non-SAH patients were enrolled in this study. We evaluated the wall enhancement of each aneurysm on postcontrast MSDE-3D-TSE images compared with precontrast images. We classified the aneurysmal wall enhancement into three groups as "Strong enhancement," "Faint enhancement," and "No enhancement." RESULTS: "Strong/Faint enhancement" of the aneurysm was detected in 73.8/24.6 % of the ruptured aneurysms and 4.8/13.3 % of the unruptured aneurysms. "No enhancement" was found in 1.6 % of the ruptured aneurysms and 81.9 % of the unruptured aneurysms. CONCLUSIONS: By magnetic resonance vessel wall imaging using the MSDE-3D-TSE sequence, wall enhancement was frequently observed on ruptured aneurysms. Therefore, aneurysmal wall enhancement may be an indicator of the ruptured condition, which is useful information for managing patients with SAH.

Overexpression of cyclin E and cyclin-dependent kinase 2 is correlated with development of hepatocellular carcinomas.

Mammalian cell cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (CDKs) and CDK inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address the role of these cell cycle proteins in hepatocellular carcinomas, we analyzed the expression of cyclin E and CDK2. A panel of livers with human hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis were used as a human experimental system. The inbred LEC (Long-Evans with a cinnamon-like coat color) rats were used as an animal experimental HCC model. Immunohistochemical staining of serial paraffin sections was performed using antibodies to cyclin E and CDK2. The results showed that cyclin E and CDK2 were concurrently overexpressed in hepatocellular carcinomas both in human and rat livers. Western blot analysis and CDK2 kinase assay demonstrated expression levels of cyclin E and CDK2 and CDK2 kinase activity, respectively, and both were shown to increase along with the development of hepatocellular carcinomas. Analysis of the correlation between expression of cyclin E and CDK2 and clinicopathological parameters revealed a significant correlation between expression of cyclin E and tumor grade (P=0.013), and PCNA index (P=0.006) as well as CDK2 expression (P=0.015). Overexpression of CDK2 tended to be associated with poorly differentiated HCCs. The results suggest that overexpression of cyclin E and CDK2 plays an important role in the development of hepatocellular carcinoma.

Cyclin-dependent kinase inhibitor p27 is related to cell proliferation and prognosis in laryngeal squamous cell carcinomas.

An immunohistochemical study of both p27 and proliferating cell nuclear antigen (PCNA) was performed on 102 cases of laryngeal squamous cell carcinomas (LSCCs), and large variations in p27 expression were found among the tumours. Reduced expression of p27 was revealed in 54 (52.9 per cent) cases and correlated with tumour size, lymph node metastasis, and clinical stage, but did not correlate with age, sex, tumour site, or tumour grade. A significant positive correlation was found between the percentage of loss of p27 expression and the PCNA index (r = 0.844, p < 0.0001). Reduced expression of p27 was significantly correlated with both reducing disease-free and overall survival by univariate analysis. By multivariate analysis, reduced expression of p27, tumour grade, tumour size, lymph node metastasis as well as clinical stage were independent prognostic factors for overall survival of LSCCs. These findings indicate that reduced expression of p27 may be correlated with the malignant biological behaviour of LSCCs.

The contribution of low affinity NGF receptor (p75NGFR) to delayed neuronal death after ischemia in the gerbil hippocampus.

The implication of low affinity nerve growth factor receptor (p75NGFR), which is believed to play a pro-apoptotic role, in delayed neuronal death (DND) after ischemia in the gerbil hippocampus was investigated. Immunohistochemistry and Western blot analysis revealed that the presence of p75 NGFR immunoreactivity (IR) was negligible in the hippocampus of the sham control gerbil but appeared clearly in CA1 neurons 3 and 4 days after 5-min transient ischemia. Terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) positive nuclei appeared when the level of p75NGFR IR increased. Furthermore, almost all TUNEL-positive CA1 neurons also costained for p75NGFR. These results suggest that p75NGFR contributes to DND after ischemia by an apoptotic mechanism.

Enhanced expression and activation of Ca(2+)/calmodulin-dependent protein kinase IV in hepatocellular carcinoma.

BACKGROUND: Ca(2+)/calmodulin-dependent protein kinase IV (CaM-kinase IV) is a multifunctional protein kinase that is expressed abundantly in the central nervous system and, to a lesser degree, in nonneuronal tissues such as the liver. In the current study, the authors demonstrated the expression of CaM-kinase IV in hepatocytes from hepatocellular carcinoma (HCC) in both humans and rats. METHODS: Immunoblotting and immunohistochemical analysis were performed to confirm the expression of CaM-kinase IV and CaM-kinase kinase in HCC occurring in both humans and rats. The kinase activity of CaM-kinase IV in the lysate of each of these liver supernatant fluids was measured using a specific substrate (peptide gamma) for this enzyme before and after phosphorylation by exogenously added CaM-kinase kinase. RESULTS: Marked positive staining of HCC hepatocytes was found and the subcellular staining pattern mainly was cytosolic. One immunoreactive band with a molecular weight of 64 kilodaltons, which was identical to an isoform of rat cerebellum CaM-kinase IV, was demonstrated by immunoblotting. Ca(2+)/calmodulin-dependent CaM-kinase IV activity was high in HCC and showed almost no difference in activity in specimens with and without CaM-kinase kinase phosphorylation. CONCLUSIONS: CaM-kinase IV was found to be expressed in HCC and might have been involved in the development of HCC. CaM-kinase IV that was expressed in cancerous hepatocytes was phosphorylated mainly by CaM-kinase kinase that also was expressed in tumor cells.

A long-term study of implanted artificial hydroxyapatite particles surrounding the carotid artery in adult dogs.

In this long-term study, we implanted HAP into adult dogs using a silicone chamber attached to the carotid artery to clarify tissue reaction to HAP implantation over a long period. We designed chambers and both hemispheres of the chambers were filled with HAP particles, and were placed around both carotid arteries of seven adult dogs. The implants were removed after 150, 300, 380 days, and histological and ultrastructual examination was undertaken. We observed bone-like tissue which was formed where HAP particles were implanted. Immunohistochemical findings showed that osteocalcin and osteonectin were as positive in the bone-like tissue as in normal bone. This study suggests that biological factors from the arterial wall might play an important role in new bone-like tissue forming, and that HAP has a strong osteoconductive ability even at heterogeneous sites.

[Chemotherapy with nedaplatin for an oral floor cancer patient undergoing chronic hemodialysis].

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, the administration of chemotherapeutic drugs to a patient with renal failure should be sufficiently considered beforehand to avoid adverse effects. A case of carcinoma of the oral floor in a 69 year-old male receiving ongoing hemodialysis due to chronic renal failure is reported. Chemotherapy was given using nedaplatin and 5-FU; surgery was performed as well. To investigate the pharmacokinetics and determine the optimal dose of nedaplatin during ongoing hemodialysis, the concentrations of free-platinum and total-platinum in serum from the patient were measured periodically. The patient received approximately one half of the dose of nedaplatin for a patient with normal renal function. Hemodialysis was performed 3 hours after the start of the administration of nedaplatin and continued for 4 hours. As a result, the maximum concentration of nedaplatin (Cmax) was about one half of the normal range. However, the value of the area under the blood concentration time curve (AUC), which is considered a target index of administration, was close to the value in patients with normal renal function. No severe side effects were observed after chemotherapy. A Grade IV pathological effect on Ohboshi-Shimosato's classification was obtained from the specimen after radical resection.

Florid cemento-osseous dysplasia. Report of a case.

A case of florid cemento-osseous dysplasia in a 16-year-old Japanese boy is presented. The lesion was unusually large and affected all four quadrants. Progressive increase in the bulk of the lesion was seen.

Osteoblastic differentiation is enhanced by rapamycin in rat osteoblast-like osteosarcoma (ROS 17/2.8) cells.

The effects of three immunosuppressants (rapamycin, FK506 and cyclosporin A) on the proliferation and differentiation of rat osteoblasts-like osteosarcoma cell line, ROS 17/2.8 (ROS) cells were examined in vitro. All immunosuppressants showed a direct inhibition on the proliferation of ROS cells with different potencies. Growth inhibition by rapamycin was stronger than that by FK506 or cyclosporin A. Rapamycin caused a significant increase in alkaline phosphatase (ALP) activity and in the expression of osteopontin and osteocalcin mRNAs. FK506 caused a moderate increase in ALP activity and a decreased expression of osteopontin mRNA. Cyclosporin A caused a decrease in ALP activity and in the expression of type 1 alpha 1 collagen mRNA. Our study indicates that rapamycin directly acts on ROS cells and induces osteoblastic differentiation, however, the effect of FK506 and cyclosporin A is weak. Rapamycin significantly enhances the differentiation induced by 1,25(OH)2-vitaminD3.

Changes in the expression of novel Cdk5 activator messenger RNA (p39nck5ai mRNA) during rat brain development.

We previously reported that a neuron-specific Cdk5 activator, p35nck5ai, was most prominent in the newborn rat brain. In the adult brain, the expression decreased in most regions except hippocampus and primary olfactory cortex. A novel neuron-specific Cdk5 activator, p39nck5ai, has been recently cloned. To clarify whether two activators were differentially distributed throughout brain development, in this study, we examined the spatial and temporal expression of p39nck5ai in the development rat brain. Northern blot analysis showed that p39nck5ai expression was low in 15-day old fetuses and newborn, and was most prominent in the 1-3 week-old rat brains. In the adult rat brain, expression declined to the same level as in newborn rat brain. In situ hybridization showed that p39nck5ai mRNA was weakly expressed in all neurons of all regions in the newborn rat brain and the transcriptional level was highest in all regions in the 3 week-old rat brain. In the adult, expression was decreased in most neurons except Purkinje and granule cells in the cerebellum which retained high levels. These results suggest that p35nck5a and p39nck5ai may have different functional roles in distinct brain regions during different states of the rat brain development.

Distribution and morphology of valves in the human external jugular vein: indications for utilization in microvascular anastomosis.

PURPOSE: This study examined the valves in the external jugular vein (EJV) that could affect microvascular anastomosis and increase the risk of thrombogenesis. MATERIALS AND METHODS: The EJVs of 57 sides from 36 cadavers aged 40 to 95 years (20 males and 16 females) were dissected. After opening the veins, the distribution and morphology of the valves were investigated using a stereoscopic microscope. The length of the valves and inner diameter of the vessels were measured and related to the location of the valves. RESULTS: Forty-nine (86%) of 57 EJVs were confluent with the subclavian vein. The EJV possessed bicuspid valves, and in 46 (93.9%) of the 49 specimens there were valves at the junction with the subclavian vein, whereas 44 (89.8%) contained valves in the middle portion of the specimen. The length of the valves was less than twice the inner diameter, and some were occasionally only rudimentary. CONCLUSION: Numerous valves exist in the middle portion of the EJV where microvascular anastomoses are performed. When valves are observed in the site of anastomosis, they can be avoided by resecting a length equal to approximately twice the inner diameter.

Morphological study of the human maxillofacial venous vasculature: examination of venous valves using the corrosion resin cast technique.

BACKGROUND: The venous drainage in the human head and neck, structures located superior to the heart, generally does not counter the force of gravity. Accordingly, venous valves in the human head have been reported to be few or nonexistent, and therefore the direction of venous drainage is variable and obscure. METHODS: We investigated whether venous valves were present in 13 heads of human adult cadavers using scanning electron microscopic observation of corrosive resin casts in the human maxillofacial region. This technique afforded the observation of the venous valves. RESULTS: Venous valves were found throughout the facial region. In particular, there were many valves distributed in the lingual, upper and lower labial, facial and pharyngeal veins. The venous valves were particularly well formed at motile parts of the maxillofacial region. CONCLUSIONS: It is suggested that these valves may aid the venous blood return and permit the blood drainage in one direction.

Anatomical study on valves of human facial veins.

The valves of the facial veins of 39 sides from 20 cadavers, aged 54-95 years, were investigated. Anatomical study of the valves is important, because the facial veins can be used for microvascular anastomosis in reconstruction in the head and neck. The present study confirmed that valves existed in the human facial veins, and were most frequently observed around the lower border of the mandible. When valves were classified into 5 types according to the morphology of the lobules, bicuspid valves were the most common (93.5%), followed by traced valves (4.1%), valve preparation (1.3%), and unicuspid valves (0.9%). However, no tricuspid valves were observed. Valves appeared most often (82.9%) at confluences with the facial veins. The length of valves in the trunk of the facial veins was twice the size of the inner diameter of the vessels in 78.4% of the cases. Therefore, when valves were observed at the anastomosis sites, the present results indicated that these valves could be avoided by resecting a length of about twice the inner diameter.

Developmental alteration and neuron-specific expression of bone morphogenetic protein-6 (BMP-6) mRNA in rodent brain.

Bone morphogenetic proteins (BMPs) are a group of proteins which induce bone formation from mesenchymal cells. The existence of BMPs in the nervous system as well as in bone tissue has recently been reported. In this study, we show that BMP-6 is neuron-specific, and describe the temporal and spatial expression patterns of BMP-6 mRNA in the developing rat and gerbil brain. Northern blot analysis showed that the BMP-6 transcript level was specifically high from newborn to 3 weeks after birth compared with those in fetal and adult rats. In situ hybridization showed that most of the neurons possessed high levels of BMP-6 mRNA in the neonatal brain, while in the adult brain, BMP-6 mRNA level was significantly decreased in most of the neurons except those in hippocampus which retained high levels. Furthermore, to show that the BMP-6 expression was specific to neurons, we induced delayed neuronal cell death and compensative glial cell proliferation in the gerbil hippocampus by transient ischemia. Our findings collectively suggest that BMP-6 is neuron-specific and may play important roles in neuronal maturation and synapse formation.