Effects of topical nipradilol, a beta-blocking agent with alpha-blocking and nitroglycerin-like activities, on aqueous humor dynamics and fundus circulation

PURPOSE: To study the effects of nipradilol, a nonselective beta-blocker with alpha 1-blocking activity and nitroglycerin-like activity, on aqueous humor dynamics and optic nerve head (ONH) circulation in albino rabbits. METHODS: Experiments were carried out during the dark phase, in conscious rabbits conditioned to a schedule of alternating 12-hour periods of light and dark. The blood-aqueous barrier permeability and the aqueous flow rate were determined fluorophotometrically. The effect on outflow to general blood circulation and uveoscleral outflow were determined by using the fluorophotometric Diamox technique, and the effect on the uveoscleral outflow was further assessed by using the anterior chamber perfusion method. The ONH circulation was estimated by using the laser speckle method. RESULTS: Unilateral topical administration of 0.25% nipradilol solution lowered intraocular pressure (IOP) with relatively weak contralateral effects in a dose-dependent manner with a maximum reduction of 6 mm Hg and an effect duration of 6 hours. Twice-daily instillation for 14 days showed no attenuation of the effects. Single instillation of 0.25% nipradilol showed no significant effect on blood-aqueous barrier permeability and decreased aqueous flow rate in the treated eye (17%; P < 0.01) and in the contralateral eye (9%, P < 0.05). Nipradilol produced no significant effect on outflow facility to general blood circulation, whereas it substantially increased uveoscleral outflow. Twice-daily 0.25% nipradilol instillation increased ONH tissue blood velocity by 13% (P < 0.01), which was probably attributable to locally penetrating drug. CONCLUSIONS: Because of its ability to lower IOP and to increase uveoscleral outflow and optic nerve head circulation in rabbits, further studies are warranted to determine whether nipradilol has potential as an antiglaucoma agent in humans.     

Modular manufacturing

This paper discusses requirements to be satisfied by future manufacturing systems and proposes a new concept of modular manufacturing to integrate intelligent and complex machines. In large-scale systems such as manufacturing systems, modularization is indispensable for clarifying logical structure and assuring a high degree of ease of construction. The parts, products and manufacturing equipments as well as the design and operating activities themselves are all described in units called modules. A manufacturing system is constructed and operated by combining these in building-block style. The creation of this manufacturing system relies on construction and operating systems that enable design and simulation in the virtual world, and production and control in the real world, in a unified approach. Hardware modules and software modules are compiled flexibly and hierarchically to fulfil specified tasks. A system in which modular manufacturing as a concept of system integration is applied to manufacturing robots is called a modular robot system. The robots are embedded in manufacturing systems as the highest application of model-based robotics.     

Synthesis of IPN-related materials from solution of polyacrylates

IPN-related materials were synthesized from solution of two acrylate polymers having epoxide. From the dynamic mechanical spectroscopy, it was difficult to distinguish IPN or semi-IPN from mechanical blend in the case of PEMA/P2EHMA system. But some possibility of IPN phenomenon was observed. In the case of PEMA/PEA system, IPN synthesized from benzene-chloroform mixed solvent showed phase separation with the matrix of PEMA. IPN synthesized from xylene, however, showed phase separation with the matrix of PEA and the transition due to PEA shifted higher by 5°C than that of homo PEA. From the results, we concluded that PEMA/PEA system synthesized by xylene showed JPN phenomenon.     

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.     

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).