-Structure of the respiratory system of the Ulodera Hynobius neblosus tokyoensis Tago, with special reference to the distribution of serotonin-immunoreactive cells in its respiratory tract epithelium

The respiratory tract epithelium in many vertebrate species has a neuroepithelial endocrine (NEE) system. This system is composed of solitary NEE cells or organoid cell groups called neuroepithelial bodies (NEBs). In response to chemical and physical stimuli, NEE cells may release bioactive substances. Serotonin, one of the biogenic amines, well-known as a constricter of smooth muscle, can be found in NEE cells, serotonin-immunoreactive cells can be used as a marker for these cells. Comparative histological studies of lower vertebrates can improve our understanding of mammalian respiratory systems. The Tokyo salamander (Hynobius neblosus tokyoensis Tago), classified as Ulodera, is particularly useful for comparative studies of respiration. In this study, the serial sections of respiratory tract of the Tokyo salamander were stained by a commonly used staining method and by an immunocytochemical method for serotonin, and the distribution of serotonin-immunoreactive cells in the respiratory tract was examined. The respiratory tract was found to be connected to the alimentary tract via an aditus laryngis, which opens on the medio-ventral side of the esophagus. The laryngotrachea was slit-like or elliptically shaped with a total length of about 3.5 mm, joining the aditus laryngis. The laryngotrachea was supported by a pair of lateral cartilages, and a fibromuscular layer was seen between the cartilages and the epithelium. In the cranial region, a laryngeal sphincter was seen around the laryngotrachea. The laryngotrachea branches into a pair of tube-like lungs, that are about 17-20 mm in length. Two apposed primary trabeclae run along the entire length of the lung wall, perpendicular to the axis, and containing the pulmonary arteries and veins. The lungs were divided into two portions: 1) an airway portion (trabeclae, septa) in which smooth muscles surrounding the large vessels were well developed, and 2) a respiratory portion which was give that name because it has well developed capillary networks that were assumed to be involved in gas exchange. The lumen of the laryngotrachea and the pulmonary airway portion contained pseudostratified cilio-mucous epithelium. In the caudaldorsal region of the laryngotrachea adjacent to the lungs, the non-ciliated respiratory epithelium was seen lining the capillaries. In cilio-mucous epithelium of the laryngotrachea, all serotonin-immunoreactive cells were solitary. They apposed to be columnar, cuboidal, triangular, oval, and flask- or spindle-shaped. Solitary serotonin-immunoreactive cells were classified "open type cell" with appical process reaching to the luminal surface and "closed type cell" insulated from the lumen by an epithelial lining. In the pulmonary airway portion, serotonin-immunoreactive cells were solitary cells and in clusters. Serotonin-immunoreactive cells were widely distributed throughout the respiratory tract, but they tended to be found mainly in the cranial portion. The density was highest in the area with the laryngeal sphincter, and decreased caudally in the laryngotrachea and lung. No serotonin-immunoreactive cells were found in the respiratory portion of the dorsal-caudal area of the laryngotrachea or in the part of the lung with non-ciliated cells. So the structure and distribution of serotonin-immunoreactive cells in the respiratory tract of the Tokyo salamander are similar to those of NEE cells and NEBs in mammalian respiratory systems. The density of serotonin-immunoreactive cells appears to be related to the distribution of smooth muscles in the fibromuscular layer and airway portion. The cells may be involved in regulation of the respiratory system. Serotonin is released in response to stimulation, which could result in constriction of the fibromuscular layer and shrinkage of the laryngotracheal cavity, and may regulate pulmonary volume by constricting smooth muscles     

Topological design considering flexibility under periodic loads

Topology optimization has been extensively considered to design the structural configuration for the stiffness maximization and the eigenfrequency maximization. In this paper, we construct a topology optimization method implementing flexibility with the time-periodic loading condition. First, the flexibility in the dynamic periodic loading is formulated using the mutual energy concept. Second, the multi-optimization problem is formulated using a new multi-objective function in order to obtain an optimal solution incorporating both flexibility and stiffness. Next, the topology optimization procedure is developed using the homogenization design method. Finally, some examples are provided to confirm the optimal design method presented here. Received January 18, 1999     

A study of hypervelocity impact on cryogenic materials

This paper reports a result of hypervelocity impact experiments on cryogenically cooled aluminum alloys and a composite material. Experiments are carried out on a target palate at 122 K. Aluminum spheres at 1.95 km/s in 50 kPa air were impinged against the target plate at cryogenic temperature and the result was compared with room temperature target plates. Hypervelocity impact (HVI) processes were visualized with shadowgraph arrangement and recorded with high-speed video camera and to ensure the temperature dependence we compared HVI tests with metal target plates with AUTODYN 2D and SPH numerical simulations. We found that cryogenic impacts created slight differences of impact damage from room temperature ones, i.e., the shape and averaged diameters of HVI crater holes were less at cryogenic impacts.     

Activities of Phosphorus in Copper‐Iron Liquid Alloys Saturated with Copper‐Iron Solid Solutions

In order to determine the activities of phosphorus and iron in liquid {Cu‐Fe‐P} alloys, the two coexisting phases of liquid {Cu‐Fe‐P} alloys + <Cu‐Fe‐P> solid solutions were brought into equilibrium with a mixture of Al₂O₃ + AlPO₄ + Fe_xAl₂O₄ at temperatures of 1416K and 1526K. The oxygen partial pressures were measured with the aid of a solid‐oxide galvanic cell of the type: (+)Mo / Mo + MoO₂/ ZrO₂(MgO) / {Cu‐Fe‐P} + <Cu‐Fe‐P> + <Al₂O₃> + <AlPO₄> + <FeAl₂O₄> / Fe(‐) The equilibrium reactions underlying the experiments can be expressed by 2[P]_cu + (5/2) (O₂) + <Al₂O₃> = 2 <AlPO₄> and x[Fe]_Cu + (1/2) (O₂) + <Al₂O₃> = <Fe_xAl₂O₄> The Henrian activity coefficient referred to 1 wt pct solution in pure liquid copper could be well expressed by the formula log f_P° = (4.46±0.40) ‐ (8.67±0.59)/(T/K). The iron activities referred to pure solid iron could be formulated as log a_Fe =‐ (0.37 ± 0.12) + (500 ±200) /(T/K).     

Expression of fibrogenic cytokines in desmoplastic malignant melanoma

OBJECTIVE: Research has confirmed substantial links between OCD and AN. Not only are there psychopathological similarities between the two syndromes, but a marked neurochemical correspondence. Extensive exercising is a common feature of AN and also has relevance in its links with OCD. There is evidence from the exercise-induced weight-loss syndrome in animals that exercise and caloric restriction, in combination, tend to increase serotonergic activity in a synergistic manner. This syndrome has been proposed as a valid model of OCD as well as for AN. To date, little research has directly tested this theory in the human condition. METHOD: Fifty-three AN patients were categorized as high-level exercisers (N = 22) or moderate/nonexercisers (N = 31) based on the frequency of their physical activity over the year before assessment. RESULTS: Exercisers scored significantly higher on a measure of OC personality characteristics, OC symptomatology, and perfectionism--a personality factor associated with the development of Obsessive-Compulsive Personality Disorder. On the other hand, there were no group differences on other salient eating disorder characteristics such as body esteem, self-esteem, or weight preoccupation. There were also no differences in degree of emaciation as indicated by Body Mass Index. CONCLUSIONS: Findings suggest that among AN patients obsessional personality characteristics are linked to high-level exercising, and that exercising is associated with a greater degree of OC symptomatology. Results are discussed in the context of current theories of AN, OCD, and some biological mechanisms.     

Aqueous chromatography utilizing pH-/temperature-responsive polymer stationary phases to separate ionic bioactive compounds

Cross-linked poly(N-isopropylacrylamide-co-acrylic acid) (poly(IPAAm-co-AAc))-grafted silica bead surfaces were prepared and applied as new column matrix materials that exploit temperature-responsive anionic chromatography to separate basic bioactive compounds, specifically catecholamine derivatives, in aqueous mobile phases. Since poly(IPAAm-co-AAc) has a well-known temperature-responsive phase transition and apparent pKa shift, polymer-grafted silica bead surfaces are expected to exhibit simultaneous hydrophilic/hydrophobic and charge density alterations under thermal stimuli. Elution behavior of catecholamine derivatives from a copolymer-modified bead packed column was monitored using aqueous mobile-phase HPLC under varying temperature and pH. Catecholamine derivatives had higher retention times on poly(IPAAm-co-AAc) columns at higher pH in comparison with those on noncharged PIPAAm reference columns, suggesting an electrostatic interaction as a separation mode. Temperature also affected the retention behavior of catecholamine derivatives. Optimal separation of four catecholamine derivatives was achieved at elevated temperature, 50 degrees C, and at pH 7.0. This is due to the increased hydrophobicity of the stationary phase as evidenced by the elution of a nonionic hydrophobic steroid. From these results, mutual influences of both electrostatic and hydrophobic interactions between basic catecholamine derivatives and pH-/temperature-responsive surfaces are noted. Consequently, elution of weakly charged bioactive compounds is readily regulated through the modulation of stationary-phase thermoresponsive hydrophilic/hydrophobic and charge density changes.     

Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC₅₀, K_i values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.