Innominate osteotomy (Salter) related to the correction of the acetabular abnormality and the prediction of the acetabular angle after operation (author's transl)]

The purpose of this paper is to know how to correct the maldirection of the acetabulum. The author devised a new system for the measurement of the degree of the forward rotation of the acetabulum. The acetabular improvement after the osteotomy is classified into two types, namely the primary and secondary improvement. The primary improvement is seen immediately after the osteotomy and the secondary improvement follows gradually. The effective factors for each of them were analyzed. The primary improvement is influenced mostly by the lateral inclination of the distal fragment. The secondary improvement was intimately correlated to the forward rotation of the acetabulum at the operation. The development of the acetabulum after operation can therefore be predicted from the post-operative X-ray film. In the case of the residual subluxation of the hip, there is about 10 degrees of acetabular elevation (frontalization), so the acetabulum should be rotated forward by more than 10 degrees in this operation.     

Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma

BACKGROUND: Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC. METHODS: The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital. RESULTS: Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease. CONCLUSIONS: From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.     

Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand.

Recent studies have revealed the essential role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) in osteoclast differentiation and activation. Adenovirus vector could efficiently transduce genes into RAW264.7 cells, which differentiate into osteoclast-like multinucleated cells in the presence of RANKL. The role of NF-kappaB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative 1kappaB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-kappaB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-kappaB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-kappaB and JNK activation are independently required for osteoclast differentiation.     

Experimental studies on the influences of physical properties of foods on the appearance of silent period in discharge of masticatory muscles

It is considered that the appearance of Silent Period (SP) during food crushing may relieve tissue injury caused by sudden change of maxillo-mandibular impactive force. In connection with this phenomenon, the relation between changes in vertical velocity of mandibular movement and the appearance of SP during food crushing was investigated. In addition, efforts were made to clarify the influences of lack of periodontal pressoreceptive information on the appearance of SP. Subjects were ten males (aged 24 to 31) with natural dentition and no masticatory dysfunction. Electromyograms were recorded on 4 lead locations: the central parts of each masseter and the anterior bundles of each temporal muscle. A Mandibular Kinesiograph and electromyograph were used to record simultaneously mandibular movement and myoelectric discharge during food crushing for the sake of comparing changes in mandibular position, vertical velocity of mandibular movement and muscular activity. Eight kinds of foods of various textures were selected for use in the examinations: dry macaroni, rice cracker, raw carrot, pickled thistle root, pickled radish, raisin, synthetic rubber block and softened chewing gum. The food was positioned on the occlusal table of the lower first molar on the habitual masticatory side of each subject. Then the subject was required to close his mouth rapidly to crush the food at a single masticatory stroke. Two experimental conditions were established in order to clarify the significance of periodontal pressoreceptive information on the appearance of SP: (1) normalcy and (2) infiltration anesthesia of the periodontal tissues of the upper and lower first-molar region on the habitual masticatory side. Results 1. SP appeared during a single masticatory stroke in response to sudden decreases or increases of vertical velocity of mandibular movement. 2. The frequency of the appearance of SP depends on the crushing characteristics of the food which is tested. For softened chewing gum and the synthetic rubber block, only one SP occurred; two SPs occurred in the cases of pickled radish and raisin; three SPs in the cases of raw carrot and pickled thistle root; and more than four SPs in the cases of dry macaroni and rice cracker. 3. Lack of periodontal pressoreceptive information resulting from anesthesia had no effect on the appearance of SP. Conclusions: 1. Sudden changes in vertical velocity of mandibular movement may depend on the crushing characteristics of the food which is crushed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Impacts of fluorouracil‐metabolizing enzymes on the outcomes of patients treated with S‐1 alone or S‐1 plus cisplatin for first‐line treatment of advanced gastric cancer

A phase III trial of S‐1 plus cisplatin (SP) versus S‐1 alone, for first‐line treatment of advanced gastric cancer (SPIRITS trial), has shown that overall survival was better in patients treated with SP than with S‐1 alone. In the present retrospective biomarker study, we aimed to develop a methodology to identify the patients with advanced gastric cancer who would respond better to S‐1 alone than SP. We studied 120 patients who received S‐1 alone or SP for first‐line chemotherapy for advanced gastric cancer, and quantitatively evaluated mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase, vascular endothelial growth factor‐A, and epidermal growth factor receptor in paraffin‐embedded specimens of primary tumors. Multivariate survival analysis in patients who received S‐1 monotherapy (66 patients) demonstrated that low TP expression (hazard ratio: 2.55 (95% CI: (1.33 to 4.89)), low TS (2.71 (1.36 to 5.37)), and high OPRT (0.33 (0.13 to 0.86)) were significant predictors of long overall survival. In patients with lower expression of both TP and TS (n = 23) than their cutoff values, the S‐1 alone group (n = 15) had longer overall survival than the SP group (n = 8; median overall survival, 18.2 months vs. 9.4 months), whereas the frequency of overall adverse events in the S‐1 alone group tended to be lower than that in SP group. Our results suggest that these biomarkers are useful for selection of patients with advanced gastric cancer in whom treatment with S‐1 alone will yield survival benefit.     

Three-dimensional imaging of the cranium and the central nervous system

Medical application of three-dimensional(3D) imaging had started from the region of skull and intracranial structures since this part of human body has not been affected by respiratory motion. Computed tomography(CT) has been the primary modality of choice for the acquisition of volumetric data for last 20 years. Recent advancement of multislice CT enabled us to obtain true isotropic volumetric data, which can be an ideal source data for 3D imaging. Another innovation in volume visualization in the development and improvement of 3D-imaging algorithm including volume rendering and multiplanar reformatted image(MPR).     

Reconstitution of rat brain mu opioid receptors with purified guanine nucleotide-binding regulatory proteins, Gi and Go.

Reconstitution of purified mu opioid receptors with purified guanine nucleotide-binding regulatory proteins (G proteins) was investigated. mu opioid receptors were purified by 6-succinylmorphine AF-AminoTOYOPEARL 650M affinity chromatography and by PBE isoelectric chromatography. The purified mu opioid receptor (pI 5.6) migrated as a single Mr 58,000 polypeptide by NaDodSO4/PAGE, a value identical to that obtained by affinity cross-linking purified mu receptors. When purified mu receptors were reconstituted with purified Gi, the G protein that mediates the inhibition of adenylate cyclase, the displacement of [3H]naloxone (a mu opioid antagonist) binding by [D-Ala2,MePhe4,Gly-ol5]enkephalin (a mu opioid agonist) was increased 215-fold; this increase was abolished by adding 100 microM (guanosine 5'-[gamma-thio]triphosphate. Similar increases in agonist displacement of [3H]naloxone binding (33-fold) and its abolition by guanosine 5'-[gamma-thio]triphosphate were observed with Go, the G protein of unknown function, but not with the v-Ki-ras protein p21. In reconstituted preparations with Gi or Go, neither [D-Pen2,D-Pen5]enkephalin (a delta opioid agonist; where Pen is penicillamine) nor U-69,593 (a kappa opioid agonist) showed displacement of the [3H]naloxone binding. In addition, the mu agonist stimulated both [3H]guanosine 5'-[beta,gamma-imido]triphosphate binding (in exchange for GDP) and the low-Km GTPase in such reconstituted preparations, with Gi and Go but not with the v-Ki-ras protein p21, in a naloxone-reversible manner. The stoichiometry was such that the stimulation of 1 mol of mu receptor led to the binding of [3H]guanosine 5'-[beta,gamma-imido]triphosphate to 2.5 mol of Gi or to 1.37 mol of Go. These results suggest that the purified mu opioid receptor is functionally coupled to Gi and Go in the reconstituted phospholipid vesicles.     

Keratin inclusions alter cytosolic protein localization in hepatocytes

Aim:  Mallory bodies have been observed in various liver diseases, however, the precise mechanism and significance of these structures have yet to be determined.
Methods:  Previously we reported on the redistribution of cytosolic proteins to keratin inclusions in mutant keratin 18-transfected cells. In this study, we treated green fluorescent protein-tagged wild-type keratin 18-transfected cells with several proteasome inhibitors and performed immunofluorescent analyses.
Results:  Proteasome inhibitors induced intracellular keratin inclusions, and desmoplakin, zonula occludens-1 and β-catenin were relocated to keratin inclusions, while theintegral membrane proteins were intact. The cytosolic proteins, 14-3-3 ζ protein and glucose-6-phosphate dehydrogenase were also relocated to inclusions. Moreover, E-cadherin, a basolateral membrane protein, was present on both the apical and basolateral domains in inclusion-containing cells.
Conclusion:  These data are identical to those in the mutant keratin 18 transfection study and suggest that keratin inclusions induced by different treatments affect localization of various cytosolic components, which may influence cellular functions performed by these proteins.     

Up-regulation of CX3CR1 on tonsillar CD8-positive cells in patients with IgA nephropathy

Although tonsillectomy are used as therapeutic options to prevent chronic renal failure in IgA nephropathy (IgAN) patients, the relationship between IgAN and tonsils is not fully proved by basic research. Recently, circulating CX3CR1-positive cells were reportedly involved in promoting hematuria in patients with IgAN. In this study, we focused on the expression of CX3CR1 in tonsillar mononuclear cells in IgAN patients. Immunohistological analysis revealed greater distribution of CX3CR1-positive cells in the inter-follicular area of tonsils in IgAN patients than in non-IgAN patients. CX3CR1-positive cells were also found in the affected renal glomerulus of IgAN patients. Flow cytometric analysis revealed the expression of CX3CR1 on tonsillar CD8-positive cells to be significantly higher in IgAN patients. CpG-oligodeoxynucleotides enhanced the expression in IgAN patients. The chemotactic response of tonsillar mononuclear cells to fractalkine was significantly higher in IgAN patients. Expression of CX3CR1 on peripheral blood CD8-positive cells in IgAN patients was significantly higher, and decreased after tonsillectomy, along with the disappearance of hematuria. These results suggest that hyper-immune response to microbial DNA enhanced the expression of CX3CR1 on tonsillar CD8-positive cells in IgAN patients, followed by the migration of the cells to renal lesions via blood circulation, resulting in the development of hematuria.