A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient for synthesis of dolichol-phosphate-mannose in mammalian cells

Dolichol-phosphate-mannose (Dol-P-Man) serves as a donor of mannosyl residues in major eukaryotic glycoconjugates. It donates four mannosyl residues in the N-linked oligosaccharide precursor and all three mannosyl residues in the core of the glycosylphosphatidylinositol anchor. In yeasts it also donates one mannose to the O-linked oligosaccharide. The yeast DPM1 gene encodes a Dol-P-Man synthase that is a transmembrane protein expressed in the endoplasmic reticulum. We cloned human and mouse homologues of DPM1, termed hDPM1 and mDPM1, respectively, both of which encode proteins of 260 amino acids, having 30% amino acid identity with yeast Dpm1 protein but lacking a hydrophobic transmembrane domain, which exists in the yeast synthase. Human and mouse DPM1 cDNA restored Dol-P-Man synthesis in mouse Thy-1-deficient mutant class E cells. Mouse class E mutant cells had an inactivating mutation in the mDPM1 gene, indicating that mDPM1 is the gene for class E mutant. In contrast, hDPM1 and mDPM1 cDNA did not complement another Dol-P-Man synthesis mutant, hamster Lec15 cells, whereas yeast DPM1 restored both mutants. Therefore, in contrast to yeast, mammalian cells require hDPM1/mDPM1 protein and a product of another gene that is defective in Lec15 mutant cells for synthesis of Dol-P-Man.     

An Improved Method for Predicting Pressure Drop along Slurry Pipeline

Based on extensive analysis of experimental data, the Kaushal and Tomita (2002) model for composite and solids concentration profiles is modified by considering the effect of particle size and efflux concentration on particle diffusivity. Using a modified model, the ratio of the homogeneously and heterogeneously distributed portion of each particle size is calculated. Pressure drop is predicted by summing the pressure drops due to homogeneously and heterogeneously distributed portions of different particle sizes. Comparison with experimental data for pressure drop shows that the proposed model gives better predictions than the models available in literature. The root-mean-square differences between predicted and measured values of pressure drop in percentage of the mean of measured values are for Wasp the et al. (1977) model: 5.0-21.8%; for the Gillies et al. (1991) model: 6.0-9.2%; for the Kaushal and Tomita (2002) model: 1.7-3.5%; and for the proposed model: 1.6-2.0%.     

Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate analysis of prognostic factors and evaluation of therapeutic modalities]

Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at Keio University Hospital between July 1981 and June 1996 were reviewed retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old, with an average age of 62.7. The primary lesion was located in the lateral wall in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14 (15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21 patients (23.1%). The patients were divided into two groups according to the initial main treatment of the primary lesion without regard to chemotherapy: 72 patients (79.1%) who received curative radiotherapy with or without salvage surgery, and 14 patients (15.4%) who underwent curative surgery with or without preoperative and/or postoperative radiation. The remaining 5 patients were treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%) received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by the Kaplan-Meier method as univariate analysis, and compared by the generalized Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five-year survival rates according to stage (UICC classification, 1987) were as follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30 cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p = 0.0274); and (3) location of primary lesion (p = 0.0400). The results of multivariate analysis by Cox's proportional hazards model identified T stage as a significant independent prognostic factor. Evaluation of the therapeutic modalities led to the following conclusions. (1) Differences in the initial treatments of the primary lesion were not reflected in the outcome. (2) Salvage surgery for residual or recurrent tumor contributed to improving the survival. The superior wall type, in particular, seemed to be a good indication for salvage surgery. (3) Although the limitations of radiotherapy are not defined clearly, we have to determine the indications for radical resection of tumors resistant to radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but there were no significant differences in survival between the group that underwent NAC and the other group in any other subset analyses. (5) Among the patients who underwent NAC, the responder (CR + PR) group showed a better five-year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but the difference was not significant.     

Orthotopic transplantation of a partial hepatic autograft in dogs

The purpose of this study was to investigate the availability of an orthotopic transplantation of partial hepatic autograft in dogs as a means of surgical training. Male mongrel dogs weighting 10-15 kg were used. The left lobe of the liver was harvested while preserving the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The remnant liver was removed while preserving the inferior vena cava using a veno-venous bypass. Orthotopic transplantation of the autograft was performed while anastomosing the left hepatic vein to the inferior vena cava, portal and arterial reconstruction, and external biliary drainage. Thirteen out of 29 dogs survived more than 48 h after transplantation. However, 6 out of 13 dogs were sacrificed after developing bile peritonitis due to a dislodgement of the biliary catheter, and only two dogs were able to survive for 7 days after transplantation. The arterial ketone body ratio recovered to 1.0 within 1 h after reperfusion, and the ratio of the dogs that survived for more than 48 h remained above 1.0 until sacrifice. Orthotopic transplantation of a partial hepatic autograft is a useful and simple procedure to train surgeons for partial liver transplantation.     

Late postirradiation occlusive vasculopathy in childhood medulloblastoma. Report of two cases

The kinetics of the interaction of Rab7 with REP-1 have been investigated using the fluorescence of GDP and GTP analogs at the active site of Rab7. The results show that REP-1 has higher affinity for the GDP bound form of Rab7 (Kd=1 nM) than for the GTP bound form (Kd=20 nM). Both affinities should still be sufficient for the formation of stable complexes in the cell. The association reaction proceeds in two steps for the GDP bound form. The initial step is fast (k+1 = ca. 10[7] M[-1] s[-1]) and concentration dependent while the second represents a slow equilibration (k+2 + k-2 = 3.5 s[-1]) which has little effect on the overall equilibrium. The difference in affinity of the two nucleotide bound forms arises from a difference in dissociation rates (0.012 s[-1] for Rab7 x GDP and 0.2 s[-1] for Rab7 x GTP).     

Novel form of atrial tachycardia originating at the atrioventricular annulus

We report two patients with reentrant atrial tachycardia that originated at the AV annulus. Atrial tachycardia originated in the posterior portion of mitral annulus in one patient (case 1) and the posterolateral portion of tricuspid annulus in one patient (case 2). Tachycardia was successfully eliminated by RF catheter ablation in both patients, with the catheter placed underneath the mitral valve in case 1 and on the tricuspid annulus in case 2. Spiky potentials were recorded in the diastolic phase of the atrium during tachycardia at the sites of successful ablation. Spiky potentials were also recorded after atrial electrogram during sinus rhythm, and showed decremental properties during atrial pacing. An accelerated atrial rhythm was observed during RF application, and tachycardia could not be induced after ablation in either patient. Tachycardia in these patients seemed to be due to reentrant tachycardia originating in the accessory AV node (Mahaim fiber) without ventricular connection.