Recent developments in processing systems for cell and tissue cultures toward therapeutic application

Innovative techniques of cell and tissue processing, based on tissue engineering, have been developed for therapeutic applications. Cell expansion and tissue reconstruction through ex vivo cultures are core processes used to produce engineered tissues with sufficient structural integrity and functionality. In manufacturing, strict management against contamination and human error is compelled due to direct use of un-sterilable products and the laboriousness of culture operations, respectively. Therefore, the development of processing systems for cell and tissue cultures is one of the critical issues for ensuring a stable process and quality of therapeutic products. However, the siting criterion of culture systems to date has not been made clear. This review article classifies some of the known processing systems into ‘sealed-chamber’ and ‘sealed-vessel’ culture systems based on the difference in their aseptic spaces, and describes the potential advantages of these systems and current states of culture systems, especially those established by Japanese companies. Moreover, on the basis of the guidelines for isolator systems used in aseptic processing for healthcare products, which are issued by the International Organization for Standardization, the siting criterion of the processing systems for cells and tissue cultures is discussed in perspective of manufacturing therapeutic products in consideration of the regulations according to the Good Manufacturing Practice.     

Blocking Probability in Link-Frame Systems from the Viewpoint of Overflow Processes

From the development of the work concerning the overflow processes due to Palm and Taḱcs, we consider the blocking probability in four-stage type systems which are used for telephone services as speech-path connecting networks in central systems. First, the events causing failure in channel matching in the system and the stochastic properties in the system are considered. After that distribution of interval-times between the instants at which the link blocking occurs is considered from the viewpoint of overflow processes, taking into consideration the above obtained results, and finally this distribution and the blocking probability are determined.     

Noncontact transverse scan rotating head recording device

A new transverse scan rotating head recording device was investigated which is capable of high speed tracking and noncontact recording. Small tracking time less than 1 ms was obtained in a reel-to-reel tape transport by the circuit technology improving the effective resolution of a reel motor tachometer. Noncontact recording capable of more than 10⁷head scans without tape wear was achieved by the development of both a pressurized air bearing female guide and a spherical monolithic head. High track density of 12 tracks/mm was also obtained by this monolithic head.     

Ultralow resistivity in the surface direction of LB heterofilms

LB heterofilms of double layer consisting of arachidic acid and 2-pentadecyl-7, 7′, 8, 8′-tetracyanoquinodimethane (C₁₅ · TCNQ) LB films were sandwiched between Al and Au thin evaporated films. Such layer structures of Al/LB heterofilm/Au were deposited on the SiO₂ insulating film of silicon wafters. Resistance in the surface direction of the above layer structure was measured by the four-point probe technique. As a result, very low resistance of 10^?2 ～ 10^?3 Ω was obtained by the electrode system of gap 3.3 mm with width 10 mm. It was clarified in the experiments that the current flowed through the LB heterofilms of about 200 ～ 30 Å in thickness; accordingly the resistivity of LB heterofilms was calculated to be 10^?8 ～ 10^?9 Ω cm. Such a value of resistivity was much smaller than the metal resistivity of 10^?5 Ω cm. Furthermore, the current through the LB film, increased up to 1.3A, was equivalent to the very high current density of 4.1 ～ 10⁵ A/cm². However, the resistance was increased suddenly by 10⁶ times at that time and the current was decreased to 3 ～ 10^?4 A. Such a switching phenomenon could be observed repeatedly. The ultraflow resistance and the very high current density observed in the LB heterofilms will be explained by the model of the potential well filled with electron gas which was generated in the LB hetero-film by the polarization of C¹⁵ · TCNQ LB film.     

Thermodynamic properties for the quaternary system H2O + CH3OH + LiBr + ZnCl2

The thermodynamic properties (solubility, vapour pressure, density, viscosity, heat capacity and heat of mixing) of the H₂O + CH₃OH + LiBr + ZnCl₂ (9:1 H₂O:CH₃OH and 1:1 LiBr:ZnCl₂ by mass) system using H₂O + CH₃OH as the working media and LiBr + ZnCl₂ as the absorbents were measured. The solubility data were obtained in the temperature range from 270.35 to 389.55 K. The measurements of vapour pressure, density, viscosity and heat capacity were carried out at various temperatures and absorbent concentrations. The differential heat of dilution and differential heat of solution at 298.15 K were measured for solutionw with absorbent concentrations from 0 to 75.2 wt%. The integral heat of mixing data at 298.15 K were obtained from both sets of experimental data. The integral heats of mixing for this quaternary system showed exothermic behaviour. The vapour pressure data were correlated with an Antoine-type equation. An empirical formula for the heat capacity was obtained from experimental data. The experimental data for the basic thermodynamic properties of this quaternary system were compared with those of the basic H₂O + LiBr system.     

Simultaneous manifestation of squamous cell carcinoma in identical twins with epidermolysis bullosa

We report a case of identical twins with recessive dystrophic epidermolysis bullosa, who developed squamous cell carcinoma in the hand at the latter half of their third decade. To our knowledge, this is the first case of manifestation of squamous cell carcinoma in identical twins and may contribute to the understanding of oncogenesis in such patients.     

Reduced mercury excretion with feces in germfree mice after oral administration of methyl mercury chloride

When methyl mercury chloride was administered orally the amount of mercury excretion with feces of germfree mice was noticeably lower than that of the control mice. Germfree mice excreted 24 percent of the administered mercury within 10 days of administration while the control mice excreted 46 percent. Mercury retention in the organs of germfree mice was slightly higher than in the control mice. These results suggest that the existence of microorganisms in animal intestines are concerned with mercury excretion in the animal body.     

Particle-Initiated Breakdown Characteristics and Reliability Improvement in SF6 Gas Insulation

Particle-initiated breakdown characteristics in SF6 gas are investigated. Breakdown voltages are greatly influenced by particle diameter especially for AC voltages, and for very fine metallic wire particles are much higher than those for moderately thick ones. The breakdown stress of a gas gap is obtained as a function of particle length and can be estimated fairly well by assuming a corona stabilizing zone. For a spacer, the electric stress which is parallel to its surface dominates surface breakdowns and the relation between the stress and particle length is experimentally determined. In order to increase breakdown voltages, the effects of both the dielectric coating on a high-voltage electrode and spacer shape are examined. Finally, the effectiveness of the dielectric coating on a grounded electrode is demonstrated to prevent particle levitation.     

Enhanced tumor metastases in rats following cryosurgery of primary tumor

The incidence of tumor metastases was studied in WKA/Hok rats after cryosurgery and surgical excision of primary tumors. When rats with syngeneic fibrosarcoma, KMT-17, were treated by cryosurgery 5 days after transplantation of the tumor, 15 out of 31 rats (48.4%) died with tumor metastases. In contrast only 4 out of 34 (11.8%) died with tumor metastasis after surgical excision. Because tumor cells either in the regional lymph nodes or in the peripheral blood were already detectable in about half of the rats treated by either cryosurgery or surgical excision, mechanical and physical control of enhanced metastasis by cryosurgery is ruled out. The development of anti-tumor immunity was delayed in the rats treated by cryosurgery as compared with that in rats treated by surgical excision. This was investigated by means of Winn's assay. A marked reduction of tumor metastasis was seen after the surgical removal of cryonecrotized tumor tissue, while implantations of cryonecrotized tumor tissue into the rats treated by surgical excision resulted in an increment of metastasis. The mechanism of the enhanced metastasis observed in this experimental investigation is discussed from an immunological point of view.