Correlation between severity of carotid stenosis and vascular reserve measured by acetazolamide brain perfusion single photon emission computed tomography.

Few studies have investigated the relationship between the degree of stenosis of the internal carotid artery (ICA) and cerebrovascular reserve (CVR). This study examined that relationship. A total of 56 ICAs in 43 patients were included. Computed tomography scan or magnetic resonance imaging showed no evidence of infarction in any of these patients. Both iodine-123-N-isopropyl-p-iodoamphetamine ((123)IMP)-single photon emission computed tomography (SPECT) in the resting state and (123)IMP-SPECT with acetazolamide (ACZ) enhancement were performed. Quantitated cerebral blood flow (CBF) images were acquired with the (123)IMP autoradiography technique. The mean CBF without ACZ administration (resting CBF) and CVR in the middle cerebral artery territory were calculated using stereotactic extraction estimation (SEE) analysis software. The degree of stenosis in the origin of the ICA was calculated from intra-arterial digital subtraction angiography. Resting CBF was not correlated with the degree of ICA stenosis; however, nonlinear regression analysis (second-order equation) showed a moderate correlation between CVR and the degree of ICA stenosis. In 72% of the cases with a CVR <30%, ICA stenosis was >74%. Using the SEE method, CVR was moderately correlated with the degree of ICA stenosis. Our findings indicate that evaluating CVR by ACZ-enhanced (123)IMP-SPECT in patients with ICA stenosis is of clinical value.

[Clinical analyses of oral squamous cell carcinoma patients showing a complete response to chemotherapy with S-1 alone].

The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1 alone. We clinically analyzed 8 oral squamous cell carcinoma patients showing a complete response(CR)to chemotherapy with S-1 alone. These patients received chemotherapy consisting of 2 weeks' administration, including 5-days' administration and 2- days' termination, following a 1-week rest. Adverse effects were observed in 4 patients. However, all of them were grade 1 toxicities. The average length of S-1 administration before achieving CR was 9. 8 ± 3. 1 weeks(3. 3 ± 1. 0 courses). Seven patients had a recurrence. The prognosis of this group was 5 deaths by local recurrence, and 1 death by lymph node metastasis. The average length of disease progression was 447. 4 ± 479. 5 days. Two patients, one who received surgery and the other who received irradiation after chemotherapy by S-1, are alive without tumors. The 1-year and 3-year disease-free survival rates were 100% and 37. 5%, respectively.

[A case of breast cancer with extensive osteonecrosis of maxilla induced by a bisphosphonate].

Here, we report a case of extensive osteonecrosis of the maxilla associated with a history of bisphosphonate (BP) therapy for management of bone metastases from breast cancer. A 66-year-old woman was referred to our hospital because of a fistulation on the right side of the maxilla in May 2005 by her dentist. The patient had a medical history of breast cancer with bone metastasis that was treated by chemotherapy with 45 mg pamidronate in 2 weekly courses for 16 months. We suspected that this rare case of osteonecrosis was caused by chemotherapy with BPs. Palliative treatments, including antibiotic therapy and local irrigation, were administered. Finally, extensive osteonecrosis of the maxilla occurred.

Diverticular Pouch of the Buccal Mucosa: A Rare Case Report.

Diverticular pouch in the oral cavity is a rare disease, and its etiology is unclear. The authors present a rare case of diverticular pouch in the buccal mucosa. A 79-year-old man visited our hospital with a chief complaint of food impaction in the right buccal mucosa. Intraoral examination revealed a pouch just inferior to the parotid papilla. Histopathological examination after excisional biopsy showed that the epithelial cells lining the pouch were continuous with the mucous membrane and a diagnosis was made of diverticular pouch of the buccal mucosa. Twenty-five months after the patient's initial visit no recurrence has been noted. Further clinico-pathological studies are required to understand diverticular disease in the buccal mucosa. This case might help dentists to become more aware of these lesions and collect data for further investigations.

Correction to: Postmortem computed tomographic features in the diagnosis of drowning: a comparison of fresh water and salt water drowning cases.

Whereas in FWDCs, a significantly larger volume and lower density of fluid in the paranasal sinuses (P = 0.0195 and P = 0.0104, respectively), lower density of fluid in the central airways (P = 0.0077), lower stomach content density (P = 0.0216), lower density in the left atrium (P = 0.0029), and a difference of density between the atria (P = 0.0019) were observed.

Postmortem computed tomographic features in the diagnosis of drowning: a comparison of fresh water and salt water drowning cases.

PURPOSE: To investigate the effectiveness of postmortem computed tomography in the diagnosis of drowning, focusing on the comparison of fresh water and salt water cases using three-dimensionally (3D) reconstructed data. MATERIALS AND METHODS: We examined features of drowning in 25 fresh water drowning cases (FWDCs; 13 men, 12 women; mean age 73.1 years; range 43-95 years), and compared these with 12 salt water drowning cases (SWDCs; 5 men, 7 women; mean age 66.0 years; range 55-77 years). Pulmonary opacities, volume and density (CT number) of accumulated fluid in the paranasal sinuses and central airways, volume of the stomach/stomach contents, and cardiac blood density were examined. RESULTS: In SWDCs, pulmonary ground-glass opacities with wholly thickened interstitium was frequently identified (P = 0.0274). Whereas in FWDCs, a significantly larger volume and lower density of fluid in the paranasal sinuses (P = 0.0195 and P = 0.0104, respectively), lower density of fluid in the central airways (P = 0.0077), lower stomach content density (P = 0.0216), lower density in the left atrium (P = 0.0029), and a difference of density between the atria (P = 0.0247) were observed. CONCLUSIONS: A lower density in the left atrium was observed in FWDCs compared to SWDCs. This finding may be helpful in differentiating between FWDCs and SWDCs.

Multiple Skp1-related proteins in Caenorhabditis elegans: diverse patterns of interaction with Cullins and F-box proteins.

BACKGROUND: The ubiquitin-proteasome pathway of proteolysis controls the abundance of specific regulatory proteins. The SCF complex is a type of ubiquitin-protein ligase (E3) that contributes to this pathway in many biological systems. In yeast and mammals, the SCF complex consists of common components, including Skp1, Cdc53/Cul1, and Rbx1, as well as variable components known as F-box proteins. Whereas only one functional Skp1 gene is present in the human genome, the genome of Caenorhabditis elegans has now been shown to contain at least 21 Skp1-related (skr) genes. The biochemical properties, expression, and function of the C. elegans SKR proteins were examined. RESULTS: Of the 17 SKR proteins examined, eight (SKR-1, -2, -3, -4, -7, -8, -9, and -10) were shown to interact with C. elegans CUL1 by yeast two-hybrid analysis or a coimmunoprecipitation assay in mammalian cells. Furthermore, SKR proteins exhibited diverse binding specificities for C. elegans F-box proteins. The tissue specificity of expression of the CUL1-interacting SKR proteins was also varied. Suppression of skr-1 or skr-2 genes by double-stranded RNA interference resulted in embryonic death, whereas that of skr-7, -8, -9, or -10 was associated with slow growth and morphological abnormalities. CONCLUSIONS: The multiple C. elegans SKR proteins exhibit marked differences in their association with Cullins and F-box proteins, in tissue specificity of expression, and in phenotypes associated with functional suppression by RNAi. At least eight of the SKR proteins may, like F-box proteins, act as variable components of the SCF complex in C. elegans.

CT features of pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVE: Our objective was to establish the CT features that are indicative of pancreatic fistula after pancreaticoduodenectomy. CONCLUSION: A fluid collection seen on CT around the pancreaticojejunostomy site and in the pancreatic bed may be caused by pancreatic fistula in patients who have undergone pancreaticoduodenectomy. CT depiction of air bubbles in the fluid at these sites may strongly suggest the diagnosis of pancreatic fistula.

[Clinical evaluation of palliative chemotherapy with S-1 for oral cancer patients].

The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1. We treated 19 advanced oral SCC patients including 8 men and 11 women with S-1. Of the 19 patients studied, two patients were classified as UICC Stage II, two patients as Stage III, 14 patients as Stage IV A, and one patient was classified as StageIV C. The ages varied from 54 to 9 1 years (mean ages; 78.3 years-old). The patients received this chemotherapy (80-120 mg/day) consisting of 2 weeks' administration including 5-days' administration and 2-days' termination (named 'Weekday-on/Weekend-off administration schedule' ) following 1 week rest. After this treatment, 7 CR and 4 PR were achieved, but the toxicities were only anorexia, leukopenia, thrombocytopenia, and uritication of NCI-CTC grade 1. The prognosis of 19 cases was 7 terminal by primary disease, 3 terminal by other disease, 7 lives with tumor bearing, and 2 lives without tumor bearing. We concluded that our novel S-1 administration method was extremely effective for oral SCC, including lymph node metastasis, providing high potential without any severe adverse effects for palliative therapy.

The dyf-3 gene encodes a novel protein required for sensory cilium formation in Caenorhabditis elegans.

Ciliated neurons in animals are important for the reception of environmental stimuli. To understand the mechanism of cilium morphogenesis in Caenorhabditis elegans, we analyzed dyf-3 mutants that are defective in uptake of a fluorescent dye and abnormal in sensory cilium structure. Expression of green fluorescent protein in sensory neurons of a dyf-3 mutant revealed that the mutant has stunted cilia and abnormal posterior projections in some sensory neurons. The dyf-3 gene encodes three proteins with different N-terminals. The largest DYF-3 protein has 404 amino acid residues that are 38% identical with those of a predicted human protein of unknown function. Expression of a functional dyf-3Colon, two colonsgfp fusion gene is detected in 26 chemosensory neurons, including six IL2 neurons, eight pairs of amphid neurons (ASE, ADF, ASG, ASH, ASI, ASJ, ASK and ADL) and two pairs of phasmid neurons (PHA and PHB). Expression of a dyf-3 cDNA in specific neurons of dyf-3 animals indicated that dyf-3 acts cell-autonomously for fluorescent dye uptake. Reduction of dyf-3Colon, two colonsgfp expression in a daf-19 mutant suggests that dyf-3 expression is regulated by DAF-19 transcription factor, and DYF-3 may be involved in the intraflagellar transport system.

Quantitative analyses of sonographic images of the parotid gland in patients with Sjögren's syndrome.

The first purpose of this study was to quantify the sonographic images of the salivary gland to differentiate the Sjögren syndrome (SS) group from the non-SS group. We included 132 patients in this study who had been referred to our department because of a suspicion of SS. A total of 91 patients fulfilled the criteria for SS, whereas the remaining 41 patients did not. We placed the regions-of-interest within the lesion. The first purpose was to evaluate which indices obtained by the texture analyses were useful for differentiating the SS group from the non-SS group. The second purpose was to evaluate the relationship between the indices and the degree of severity in the SS group. Out of the several indices evaluated, Hurst coefficients, obtained by fractal analysis, of SS group were found to be significantly lower than those of the non-SS group. Moreover, the Hurst coefficient was associated with the degree of destruction of the parotid gland as assessed by sialography. The Hurst coefficient of a globular stage and an advanced stage were both significantly lower than that of a normal pattern, whereas the Hurst coefficient of a punctate stage was almost similar to that of the normal stage. The Hurst coefficient showed a very weak correlation with the results of either the gum test or serologic tests.

Osteochondroma in the mandibular condyle that caused facial asymmetry: a case report.

Osteochondroma is the most common benign tumor of the axial skeleton, though it is rarely found in the oral and maxillofacial regions. Reported is a case of osteochondroma affecting the mandibular condyle of a 22-year-old Japanese woman. The patient visited the hospital with the chief complaint of facial asymmetry. She had pain with clicking on her right temporomandibular joint (TMJ), resulting in trismus and facial asymmetry with a chin deviation to the left side. Her maximum jaw opening was 34 mm, with moderate left TMJ tenderness. There was Class I occlusion without open bite. Panoramic radiography and computed tomography (CT) revealed an enlarged right mandibular condylar head. Magnetic resonance imaging (MRI) also showed an enlarged condyle with hyperintense bone marrow on a T2-weighted image. Condylectomy and condyloplasty were performed. Surgical specimen of the lesion revealed osteochondroma of the mandibular condyle head. Two months after the initial surgery, facial asymmetry was surgically corrected by Le Fort I osteotomy and chin reduction. The patient was discharged from the hospital with no subjective complaints. At the time of this report, the patient had been followed up for seven months, and there had been no evidence of recurrence.

Gene and peptide analyses of newly defined lung cancer antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes.

We investigated tumor antigens recognized by HLA-A2402-restricted CTLs established from T cells infiltrating into lung adenocarcinoma. We report here three newly identified tumor antigen genes, including one unreported gene, temporarily referred to as clone 83, and two known genes, BTB domain containing 2 (BTBD2) and hairpin-binding protein. These genes were preferentially expressed in most of the cell lines of lung cancer and also of ovarian cancer and renal cell carcinoma at the mRNA level. The expression of these genes was confirmed in lung and other cancer tissue specimens. In normal tissues, clone 83 was expressed only in the colon, and hairpin-binding protein was not expressed at all, whereas BTBD2 was ubiquitously expressed. Clone 83, BTBD2, and hairpin-binding protein encoded two, one, and one epitope peptides that can be recognized by HLA-A2402-restricted CTLs, respectively. These epitope peptides possessed the ability to induce HLA-A24-restricted tumor-specific CTLs after in vitro stimulation in a culture of peripheral blood mononuclear cells from patients with lung cancer. These results suggest that these genes and peptides are potential candidates for cancer vaccines in HLA-A24(+) patients with lung cancer.

Immediate early response gene X-1, a stress-inducible antiapoptotic gene, encodes cytotoxic T-lymphocyte (CTL) epitopes capable of inducing human leukocyte antigen-A33-restricted and tumor-reactive CTLs in gastric cancer patients.

Peptide-based vaccine therapy, which is designed to elicit T-cell immunity against tumors, is an attractive approach for the treatment of cancer patients. To provide a scientific basis for peptide therapy, an increasing number of CTL-directed peptides have been identified, and some of them have been tried as antigen-specific immunotherapy in the past decade. Only a few studies, however, have been performed on such peptides restricted with alleles other than HLA-A2 and -A24. In the present study, we show that immediate early response gene X-1 (IEX-1), a stress-inducible protein associated with the regulation of cell proliferation and apoptosis, produces antigenic epitopes recognized by 850B-CTLs, HLA-A33-restricted CTLs newly established from T cells infiltrating into gastric adenocarcinoma. The IEX-1 gene was highly expressed in most cell lines and tissues from various types of cancer at both the mRNA and protein levels. However, it was not expressed at the protein level in any normal epithelium or connective tissues tested. Three IEX-1-derived peptides at positions 47-56, 61-69, and 65-73, which were recognized by the 850B-CTLs, could induce CD8(+) peptide-specific CTL reaction to tumor cells from HLA-A33(+) gastric cancer patients and other epithelial cancer patients, but not from healthy donors, in an HLA class I-restricted manner. Because increased expression of IEX-1 is suggested to be involved in the resistance to apoptosis and in the proliferation of cancer cells, these antigenic peptides could be potent candidates for peptide-based specific immunotherapy against HLA-A33(+) gastric cancer and other epithelial cancers.

The C. elegans ceh-36 gene encodes a putative homemodomain transcription factor involved in chemosensory functions of ASE and AWC neurons.

Chemotaxis to water-soluble chemicals such as sodium ion is an important behavior of Caenorhabditis elegans for seeking food, and ASE chemosensory neurons have a major role in this behavior. We isolated mutants defective in chemotaxis to sodium acetate. We show here that among them ks86 had a mutation in the ceh-36 gene. ceh-36 :: gfp reporter constructs were expressed in ASE and AWC neurons. In a mutant of the che-1 gene, which encodes another transcription factor and is required for specification of ASE neurons, expression of the ceh-36 :: gfp reporter in ASE is lost. This indicates that the ceh-36 gene functions downstream of the che-1 gene in ASE. In the ceh-36(ks86) mutant, expression of the tax-2 gene encoding a cyclic nucleotide-gated channel was reduced in ASE and AWC. This affords an explanation for defects of the ceh-36 mutant in the chemotaxis mediated by ASE and AWC. When a ceh-36 cDNA was expressed in an adult ceh-36 mutant by a heat shock promoter, chemotaxis to sodium acetate was recovered. These results suggest that ceh-36 is required for functions, and not for development, of ASE.

Ran, a small GTPase gene, encodes cytotoxic T lymphocyte (CTL) epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in cancer patients.

PURPOSE: The purpose is to identify a gene coding for tumor-associated antigen and peptide capable of inducing CTLs reactive to tumor cells with a HLA-A33-restricted fashion to provide scientific basis for specific immunotherapy to HLA-A33+ cancer patients. EXPERIMENTAL DESIGN: An expression gene-cloning method was used to identify the tumor-associated antigen gene. Northern blot analysis and immunohistochemistry were used to examine the mRNA and protein expression levels in various cells and tissues, respectively. Synthetic peptides were examined for their ability to induce HLA-A33+ tumor-reactive CTLs in peripheral blood mononuclear cells from cancer patients. RESULT: A gene of small GTPase, Ran, which controls the cell cycle through the regulation of nucleocytoplasmic transport, mitotic spindle organization, and nuclear envelope formation, was found to encode epitopes recognized by the HLA-A33-restricted CTLs established from T cells infiltrating into gastric adenocarcinoma. The expression of the Ran gene was increased in most cancer cell lines and cancer tissues at both the mRNA and protein levels. However, it was not enhanced in the surrounding normal cells or tissues. It was also undetectable in normal tissues as far as tested. Ran-derived peptides at positions 48-56 and 87-95 could induce CD8+ peptide-specific CTLs reactive to tumor cells from HLA-A33+ epithelial cancer patients in a HLA class I-restricted manner. CONCLUSIONS: Because of its increased expression in cancer cells and involvement in malignant transformation and/or the enhanced proliferation of cancer cells, the two Ran-directed peptides could be potent candidates in use for specific immunotherapy against HLA-A33+ epithelial cancers.

The Importance of cGMP Signaling in Sensory Cilia for Body Size Regulation in Caenorhabditis elegans.

The body size of Caenorhabditis elegans is thought to be controlled by sensory inputs because many mutants with sensory cilium structure defects exhibit small body size. The EGL-4 cGMP-dependent protein kinase acts in sensory neurons to reduce body size when animals fail to perceive sensory signals. In addition to body size control, EGL-4 regulates various other behavioral and developmental pathways, including those involved in the regulation of egg laying and chemotaxis behavior. Here we have identified gcy-12, which encodes a receptor-type guanylyl cyclase, as a gene involved in the sensory regulation of body size. Analyses with GFP fusion constructs showed that gcy-12 is expressed in several sensory neurons and localizes to sensory cilia. Genetic analyses indicated that GCY-12 acts upstream of EGL-4 in body size control but does not affect other EGL-4 functions. Our studies indicate that the function of the GCY-12 guanylyl cyclase is to provide cGMP to the EGL-4 cGMP-dependent kinase only for limited tasks including body size regulation. We also found that the PDE-2 cyclic nucleotide phosphodiesterase negatively regulates EGL-4 in controlling body size. Thus, the cGMP level is precisely controlled by GCY-12 and PDE-2 to determine body size through EGL-4, and the defects in the sensory cilium structure may disturb the balanced control of the cGMP level. The large number of guanylyl cyclases encoded in the C. elegans genome suggests that EGL-4 exerts pleiotropic effects by partnering with different guanylyl cyclases for different downstream functions.

Distinct roles of the Src family kinases, SRC-1 and KIN-22, that are negatively regulated by CSK-1 in C. elegans.

To elucidate the primitive roles of the Src family kinases (SFKs), here we characterized Caenorhabditis elegans orthologues of SFKs (src-1 and kin-22) and their regulator kinase Csk (csk-1). SRC-1 and KIN-22 possess the C-terminal regulatory tyrosines characteristic of SFKs, and their activities are negatively regulated by CSK-1 in a yeast expression system. The src-1 and csk-1 genes are co-expressed in some head neurons, the anchor cell and the tail region, while kin-22 and csk-1 genes are co-expressed in pharyngeal muscles and tail region. Expression of KIN-22 induced morphological defects in the pharynx, whereas expression of SRC-1 did not show any overt phenotype in adult. RNA interference of src-1, but not that of kin-22, caused a developmental arrest in early development. These results suggest that SRC-1 and KIN-22 play distinct roles under the control of CSK-1.

Spontaneous regression of extranodal malignant lymphoma occurred in the gingiva.

The spontaneous regression of malignant neoplasm is an extremely rare event. Here we report a case of extranodal malignant lymphoma occurring in the upper gingiva, which regressed spontaneously. A 78-year-old female had noticed a diffuse bucco-lingual swelling of the left maxillary gingiva in the incisor regions for a month, and she visited our department on 20 January 1999. Intraoral examination revealed diffuse swelling and redness in the maxillary gingiva of the incisor regions. Cervical and underarm lymphadenopathy was not detected. Surgical biopsy of the swollen gingiva revealed a malignant lymphoma, with diffuse large cells, B cell type. She was clinically staged as IE. After biopsy, the tumor spontaneously decreased in size; finally, the mass completely disappeared after 3 weeks. After regression, the lesions were externally irradiated with 30 Gy total dose. The patient has been free from disease for 36 months after regression.

Spinal hyperostosis as an important sign indicating spine injuries on postmortem computed tomography.

Although spine injuries are not always detectable on postmortem computed tomography (PMCT), spinal hyperostosis, an important risk factor for spine injury, is relatively easily detectable on PMCT. We therefore examined the utility of the detection of spinal hyperostosis on PMCT as an indicator of spine injury. Full-body PMCT images of 88 autopsy cases with a bruise on the face or forehead but no identifiable skull fracture were reviewed prior to autopsy for the identification and classification of spinal hyperostosis. Spine injuries were observed in 56.0% of cases with spinal hyperostosis and 1.6% of cases without spinal hyperostosis. Among the cases with spinal hyperostosis, spine injuries were observed in 66.7% of cases at stage 2 or 3 and in 88.9% of cases at stage 3. Spine injuries were diagnosed on PMCT in 33.3% of cases prior to autopsy. A significant association was found between spinal hyperostosis and presence of spine injury that cannot be detected on PMCT, indicating that the identification of spinal hyperostosis on PMCT may assist in detecting spine injuries. This finding suggests that investigation of the presence of spine injury based on the identification of spinal hyperostosis on PMCT may assist in determining the correct cause of death by autopsy.