MR Imaging Findings of Carcinoma Ex Pleomorphic Adenoma Related to Extracapsular Invasion and Prognosis.

BACKGROUND AND PURPOSE: MR imaging can reflect the pathologic progression of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to identify the imaging findings related to extracapsular invasion of CXPA. Additionally, the pathologic background of these findings was investigated. MATERIALS AND METHODS: This retrospective study included 37 patients with histologically confirmed CXPA. Three radiologists independently evaluated whether the CXPA showed the following characteristic MR imaging findings: border, capsule, the corona sign on fat-saturated T2WI and contrast-enhanced fat-saturated T1WI, and the black ring sign. The corona sign appeared larger on fat-saturated and/or contrast-enhanced fat-saturated T1WI than on T1WI. The black ring sign was defined as an intratumoral nodule with a thick low-intensity rim on T2WI. Interreader agreement of the visual assessment was performed using κ analysis, and MR imaging and histopathologic findings were also correlated. Kaplan-Meier survival and the log-rank test were used to estimate the 3-year disease-free survival. RESULTS: MR imaging findings, especially peritumoral findings, showed a significant difference between invasive and noninvasive CXPA. The reliability was poor for the border and capsule. In contrast, it was good for the corona sign on fat-saturated and contrast-enhanced fat-saturated T1WI and the black ring sign. Pathologically, the corona sign reflected the invasiveness of the tumor and inflammatory cells, while the black ring sign reflected hyalinization or fibrosis. The corona sign also showed a significant difference in the 3-year disease-free survival. CONCLUSIONS: MR imaging findings, including the corona and black ring signs, reliably differentiated invasive and noninvasive CXPA. The corona sign can be used as a prognostic factor for CXPA.

Evaluation of cervical myelopathy using apparent diffusion coefficient measured by diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Intramedullary high signal intensity on T2-weighted imaging was frequently observed in patients with CSM, although this finding does not well correlate with severity or prognosis of CSM. Instead of this nonquantitative information, another measure for CSM is desired. The work was focused primarily on assessing the relationships between ADC values and clinical and radiologic severity for the diagnosis of CSM. MATERIALS AND METHODS: The relationship between ADC values measured in the spinal cord at 322 intervertebral levels of 66 patients and clinical factors were analyzed. RESULTS: ADC values in the spinal cord significantly increased with the degree of spinal cord compression and decreased with time after decompression surgery. Patients with higher ADC values had lower preoperative JOA scores and tended to show poorer clinical recovery. CONCLUSIONS: ADC values appear to indicate the severity of spinal cord compression and clinical recovery after decompression surgery, so spondylotic myelopathy may partly be predicted preoperatively by using ADC values.

Head and neck MRI of Kimura disease.

OBJECTIVES: The purpose of our study was to describe the MR appearance of Kimura disease and to interpret the differences in appearance from malignant parotid gland tumours. METHODS: MR studies of seven patients with Kimura disease were reviewed. The MR studies included T(1) weighted, T(2) weighted, short tau inversion-recovery, diffusion-weighted (DW) and dynamic contrast-enhanced imaging. RESULTS: Typical Kimura disease featured subcutaneous lesions, continuously infiltrated parotid lesions from the subcutaneous lesions with or without intraparotid lymphadenopathies, and reactive cervical lymphadenopathies. The subcutaneous lesions showed gradual upward enhancement on dynamic contrast-enhanced MR images. Reactive lymph nodes showed early enhancement on contrast-enhanced MR images and marked high intensity and low apparent diffusion coefficient values on DW images. CONCLUSION: An indication for making the diagnosis of Kimura disease should be the subcutaneous tissue of the head and neck showing gradual upward enhancement on dynamic contrast-enhanced MRI and a lack of high intensity on DW images, associated with reactive lymph nodes.

Diagnostic value of spinal MR imaging in spontaneous intracranial hypotension syndrome.

BACKGROUND AND PURPOSE: Spontaneous intracranial hypotension (SIH) presents with orthostatic headache, and the diagnosis is made on the basis of low CSF pressure and brain MR imaging findings characteristic of the disorder. However, a broad spectrum of symptoms and MR imaging findings of SIH is recognized, and some cases have no typical MR imaging abnormalities. SIH is believed to be caused by CSF leakage from the spinal dural sac, whereas the usefulness of MR imaging of the spine remains unclear. Our aim was to elucidate the diagnostic value of brain and spinal MR imaging MATERIALS AND METHODS: The sensitivities for the detection of SIH were retrospectively evaluated in 18 patients with SIH treated in our institutions between January 1998 and August 2007. RESULTS: Brain MR imaging detected abnormalities in 15 of the 18 patients (83%): diffuse pachymeningeal enhancement in 15 (83%), descent of the cerebellar tonsil in 13 (72%), brain stem sagging in 13 (72%), enlargement of the pituitary gland in 12 (67%), and subdural fluid collection in 13 (72%). Spinal MR imaging detected abnormalities in 17 of the 18 patients (94%): distention of the epidural veins in 14 (78%), epidural fluid collection on fat-saturated T2-weighted images in 16 (89%), and abnormal visualization of the nerve root sleeve in only 1 (6%). The sensitivity for SIH was 83% for brain MR imaging and 94% for spinal MR imaging. CONCLUSIONS: Spinal MR imaging is useful for the diagnosis of SIH, especially in the early stage.

Immunohistological studies on the distribution of learning-related peptides in the central nervous system of conditioned Lymnaea.

Behavioral conditioning in Lymnaea increased the amount of immunolabeling in the central nervous system for the memory-associated protein calexcitin. The staining level of anti-calexcitin positive neurons was always stronger in conditioned animals than in naive animals. In the visuo-vestibular conditioned animals, right-parietal and visceral group neurons as well as withdrawal-related neurons were positively stained with anti-calexcitin antibody. In taste-aversion conditioned animals, right-parietal visceral G-group neurons and withdrawal-related neurons were selectively stained. These neurons are candidate neurons for modulation by these conditioning paradigms.

Neurophysiological analysis of visuo-vestibular conditioning in Lymnaea stagnalis.

Lymnaea are capable of learning an association between light and rotation. The conditioning paradigm to produce this association and the unconditioned escape response are the same for both Lymnaea and Hermissenda, but the underlying neural mechanisms appear to differ between the two species due to differences in the organization and function of their visuo- and vestibular-sensory systems. The RPeD11 interneuron in Lymnaea controls withdrawal behavior. We analyzed the electrophysiologic characteristics of the RPeD11 and observed an increase in cell excitability; that is, spontaneous activity of the postsynaptic potential in the RpeD11 was increased in conditioned animals after learning acquisition.

Relationship between developmental synaptic modulation and conditioning-induced synaptic change in Lymnaea.

Though adult Lymnaea are bimodal breathers, young animals breathe mainly through the skin and adults through the lung. Operant conditioning changes adult breathing behavior from aerial to cutaneous. We hypothesized that this behavioral change is caused by alterations in the neuronal circuit during both development and conditioning. We focused our study on whether the synaptic connection between RPeD1 and RPA6 neurons is modulated during development and conditioning. Our findings indicated that the RPeD1 has an excitatory monosynaptic contact with the RPA6 in young naive and operantly-conditioned adult animals. The relationship of this contact was well correlated with their respiratory behavior.

Decreased diameter of the optic nerve sheath associated with CSF hypovolemia.

The subarachnoid space around the optic nerve can be detected by fat-saturated T2-weighted MR imaging of the orbit, and dilation of this space reflects increased intracranial pressure. We examined 3 patients with CSF hypovolemia with MR imaging of the orbit and measured the optic nerve sheath diameter before and after treatment. We showed that the subarachnoid space is decreased in patients with CSF hypovolemia and the usefulness of this finding.

Tracer clearance in radionuclide cisternography in patients with spontaneous intracranial hypotension.

We semiquantitatively analysed radionuclide cisternography in three patients with spontaneous cerebrospinal fluid (CSF) leakage diagnosed by typical symptoms and magnetic resonance imaging findings before and several months after treatment with epidural blood patch. Radioactivity in the whole CSF space was measured immediately after and at 1, 5, 7 and 24 h after intrathecal injection of (111)In-diethylenetriaminepentaacetic acid (DTPA). Initial findings included the vague appearance of leakage in the thoracic spine in two patients, early bladder filling at 1 h in one and a lack of tracer filling into the high cranial convexity in all three. The radioactivity count rapidly decreased within several hours after injection and reached 20% of the initial value at 24 h. In contrast, no rapid decrease was observed after treatment and more than 50% of tracer remained at 24 h after injection. Semiquantitative analysis of tracer clearance may provide additional information in the diagnosis of CSF leakage, especially with no obvious qualitative findings.

Acceleration of de novo cholesterol synthesis in the epidermis influences desquamation of the stratum corneum in aged mice.

Cholesterol, a component of intercellular lipids, is important for stratum corneum (SC) homeostasis, including its barrier function and desquamation. However, cholesterologenesis in the epidermis decreases under basal conditions with aging. We found that the number of horny layers in murine SC increased with the decrease of desquamation in the outermost corneocytes associated with aging. The cholesterol content decreased and the cholesterol sulfate content increased in the horny layer with aging, which resulted in an increase in the ratio of cholesterol sulfate to cholesterol. Moreover, we investigated the effects of accelerated cholesterologenesis on desquamation in aged murine skin following topical application of mevalonic acid. The ratio of cholesterol sulfate to cholesterol in aged murine SC significantly decreased following topical treatment with mevalonic acid, which resulted from an increase in cholesterol content via the acceleration of cholesterologenesis. Treatment with mevalonic acid also significantly reduced the number of cell layers in the SC along with the acceleration of desquamation, as measured by desmoglein I content, corneocyte surface area and proteinase activity. These results indicate that an improvement in the ratio of cholesterol sulfate to cholesterol content by de novo cholesterologenesis may be important for desquamation of the SC in aged epidermis.

Effects of glycolic acid on desquamation-regulating proteinases in human stratum corneum.

In order to investigate the mechanism of glycolic acid (GA) function in human stratum corneum, we monitored changes in cathepsin D-like (CD) and chymotrypsin-like (SCCE) proteinases for 3 weeks following topical GA application (50% w/v, pH 0.9) for 30 min to human skin. In the early phase, weakened stratum corneum cohesion in the lower layers was observed on day 2 and the amount of active CD in the upper layer of the stratum corneum was significantly decreased from 30 min until day 2, whereas that in the lower layer remained normal. In contrast, the amount of active SCCE showed no change during the experimental period. The surface pH of the stratum corneum drastically decreased to pH 2 at 30 min and slightly recovered to around pH 3 until 1 day after treatment. From 9 to 19 days, a decrease in corneocyte cell area and a remarkable long-term increase in the amount of active CD in the upper layer were observed. In an in vitro study, the activities of desquamation-regulating proteinases were shown to have remarkably increased at around pH 3, due to activation of CD at its optimal pH. These results suggest that GA functions via at least two different mechanisms, acute activation of CD in the lower layer by acidification around pH 3, along with inactivation of CD in the upper layer, and long-term enhancement of de novo CD production in the few weeks following GA treatment.

Intramedullary spinal cord germinoma expresses the protooncogene c-kit.

A 33-year-old woman first noticed numbness in the both lower extremities and the numbness gradually extended up to the thorax. Magnetic resonance (MR) imaging demonstrated a mass with moderate and heterogeneous enhancement and peritumoural intramedullary cysts in the spinal cord at the T-1 to T-3 levels. The tumour was explored partially and intra-operative pathological examination demonstrated the so-called "two-cell pattern" typical of germinoma. The margin of the tumour was not clear. Histological examination showed germinoma with strong c-kit protein expression on the tumour cell surface. Chemotherapy and radiation therapy were given following surgery. Her neurological deficits were improved but not resolved.

Cathepsin D, but not cathepsin E, degrades desmosomes during epidermal desquamation.

BACKGROUND: We previously reported that an ambient aspartic proteinase is crucial to desquamation of the stratum corneum at pH 5. Identification of this aspartic proteinase by using enzyme inhibitors suggested it to be cathepsin D, although we could not exclude cathepsin E. OBJECTIVES: To determine the identity of this aspartic proteinase and its distribution within the stratum corneum. METHODS: We measured enzyme activities of cathepsin D and cathepsin E in the salt and detergent extracts from callus stratum corneum, using a fluorogenic peptide as a substrate and comparing the effect of addition of Ascaris pepsin inhibitor (specific for cathepsin E) with that of pepstatin A (which inhibits both cathepsin D and cathepsin E). Both enzymes were then extracted and purified from plantar stratum corneum samples and identified by Western blotting. Immunofluorescence microscopy was used to investigate the localization of proteinases within human plantar stratum corneum sample sections. RESULTS: We found that 20% of total aspartic proteinase activity could be attributed to cathepsin E, the remainder to cathepsin D. Two subunits of cathepsin D were identified, a mature active form at 33 kDa and an intermediate active form at 48 kDa; cathepsin E was also identified at 48 kDa, although in a stained band 10-fold weaker in the immunoblot. Immunofluorescence microscopy showed the antibody to cathepsin D to be localized in the lipid envelopes of the stratum corneum, whereas that to cathepsin E stained the tissue diffusely. The labelling for cathepsin D was similar to that observed for desmosomes, and immunoelectron microscopy confirmed that cathepsin D was present on desmosomes. On the other hand, cathepsin E occurred intracellularly within the squames. CONCLUSIONS: We conclude that cathepsin D, and not cathepsin E, causes desquamation by degrading desmosomes.

Suppression of melanogenesis by induction of endogenous intracellular metallothionein in human melanocytes.

Nitric oxide (NO) is a potent intercellular mediator of melanogenesis, whereas metallothionein (MT) is an inducible intracellular antioxidant that has been reported to scavenge NO. We investigated the existence and induction of MT in melanocytes, and its inhibitory effect on NO-induced melanogenesis. The expression of MT was detected in melanocytes, however, at a lower level than in keratinocytes, and its induction was possible by the addition of zinc chloride. Further, an NO-stimulated increase of tyrosinase activity in melanocytes was remarkably suppressed, when MT was induced prior to NO stimulation. Melanogenesis was also suppressed, when dexamethasone was used to induce MT. However, an NO-stimulated increase of tyrosinase expression was not suppressed at the gene and protein level, when MT was induced in melanocytes. The same suppressive effect of melanogenesis was also observed, when alpha-melanocyte-stimulating hormone or endothelin-1 was used as a stimulator. Because these results implied a mechanism other than NO scavenging to explain the suppressive effect of MT induction on melanogenesis, the direct inhibition of tyrosinase by MT was examined. Melanosome fractions were prepared from melanocytes, whose melanogenesis was suppressed by the induction of MT. Tyrosinase suppression was observed in the melanosome fractions, which was neutralized by the addition of anti-MT antibody. These results suggest that MT induction may be effective to suppress melanogenesis stimulated by NO as well as other melanogens, and these suppressive effects might be due to a direct inhibition of tyrosinase activity in melanosome and not a scavenging effect of NO.

Objective determination of fatigue development following sun exposure using Advanced Trail Making Test.

Sun exposure during leisure activity evokes fatigue. We employed the Advanced Trail Making Test (ATMT), a recently developed objective method of evaluating brain function performance used to measure mental fatigue, for objective determination of fatigue development caused by solar exposure to the human body. First, a survey of consumer awareness was performed, and fatigue development from solar exposure was generally recognized in both summer and spring. In the field test, 15 males (26-41 years old) received sun exposure equivalent to 100 kJ m(-2) of ultraviolet radiation three to four times each day for 3 days, during which the subjects wore a short sleeve shirt and a short pant, and covered their head with a towel. A significant increase in scores for subjective sense of fatigue was observed in the evening of all 3 days following sun exposure and on the fourth day, which had no exposure, as well as in the morning of the third and fourth days, as compared with those periods during the control week, which did not have experimental solar exposure. ATMT showed a significant increase in average value in the evening of the first and second days following sun exposure, as well as in the morning of the third and fourth days. In addition, increases in body temperature and heart rate were observed during the exposure periods. The results of multiple regression analysis of subjective feelings showed that fatigue caused by solar exposure was qualitatively different from that in the control week. These results suggest that brain function performance declined following solar exposure as did fatigue development. ATMT results may be useful for quantitative and objective evaluation of mental fatigue caused by sun exposure, along with development of sun care products for the prevention of solar-caused fatigue.

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Anatomical variations of the ten triangles around the cavernous sinus.

The dimensions of the 10 triangles around the cavernous sinus were measured to define the anatomical characteristics of the triangles and to compare their consistency in shape and area. Twelve tissue blocks containing the bilateral cavernous sinuses and medial two-thirds of the middle cranial fossae were obtained from Japanese adults at autopsy, fixed to a stereotactic frame, and examined with an operative microscope. The dimensions of each triangle were measured with calipers and compared, based on the same point and border. The anteromedial triangle and the superolateral (Parkinson's) triangle were more consistent in shape than the paramedial and oculomotor triangles, but the oculomotor triangle was larger in area than these other triangles. The posteromedial (Kawase's) triangle was more consistent in shape and larger than the anterolateral, lateral, and the posterolateral (Glasscock's) triangles. The anteromedial and superolateral (Parkinson's) triangles are important for the combined epi- and subdural approach to cavernous sinus lesions. The posteromedial (Kawase's) triangle is important for gaining access to the posterior cranial fossa from the middle cranial fossa.

Application of SEM-modified X-ray microscope to entomology and histology, and effects of X-ray coherence in imaging.

A projection X-ray microscope has been constructed by modifying a scanning electron microscope (HITACHI S-2500CX). Characteristic internal structures and their changes in an aphid, a fly, an ant, a water bear and a beetle are observed first, non-destructively, by X-ray microscope. Stereo-pair X-ray micrographs of Golgi-stained sections of porcine liver show a network of bile canaliculi and stellate cells. The very clear micrographs presented indicate the usefulness of the microscope in studies of entomology and histology. In some micrographs, very thin whiskers or hairs are visible, which suggests that a phase-contrast effect is present in the imaging. X-ray micrographs of an ant hair taken at various distances between the X-ray source and the specimen, D(s), indicate that the image enhancement due to the phase contrast increases with increasing D(s). Degree of the lateral coherence of X-rays of wave length 0.1 nm is theoretically estimated near the hair, with the result that the coherence increases from about zero (almost complete incoherence) at D(s) = 0.1 mm to about unity (almost complete coherence) at D(s) = 6 mm, in agreement with the observation.

Involvement of nitric oxide in UVB-induced pigmentation in guinea pig skin.

Ultraviolet (UV) B irradiation evokes erythema and delayed pigmentation in skin, where a variety of toxic and modulating events are known to be involved. Nitric oxide (NO) is generated from L-arginine by NO synthases (NOS). Production of NO is enhanced in response to UVB-stimulation and has an important role in the development of erythema. NO has recently been demonstrated as a melanogen which stimulates melanocytes in vitro, however, no known in vivo data has been reported to support this finding. In this study, we investigated the contribution of NO with UV-induced pigmentation in an animal model using an NOS inhibitor. UVB-induced erythema in guinea pig skin was reduced when an NOS inhibitor, L-NAME (N-nitro-L-arginine methylester hydrochloride), was topically applied to the skin daily, beginning 3 days before UVB-irradiation. Delayed pigmentation and an increased number of DOPA-positive melanocytes in the skin were markedly suppressed by sequential daily treatment with L-NAME. Furthermore, melanin content 13 days after UVB-irradiation was significantly lower in skin treated with L-NAME than in the controls. In contrast, D-NAME (N-nitro-D-arginine methylester hydrochloride), an ineffective isomer of L-NAME, demonstrated no effect on these UV-induced skin responses. These results suggest that NO production may contribute to the regulation of UVB-induced pigmentation.