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The effect of three nebulizers, Nisshou and LC plus, were compared by the particle size and amount of inhalation. The improvement of FEV1 at 15 minutes after the inhalation was significantly higher in LC plus than Nisshou (MMD: 7.43microm, 10.76microm). The amount of inhlation were compared between Nisshou with/without Y tube and LC plus nebulizer with/without LC valve system. Nisshou nebulizer with Y tube and LC plus nebulizer with LC valve systems were significantly better than that of LC plus nebulizer without LC valve system. Small loss of inhalation gave us better efficacy. The urinary excretion of disodium cromoglycate (DSCG) was highest in LC plus with LC valve system, Nisshou with Y tube and lowest in Nisshou without Y tube. The elecctric nebulizers produced better in MMD of 5microm and a smaller loss of inhalation. These results suggested that MMD less than 5microm and small loss from nebulizer are very important for inhalation therapy.

Osteoclastogenesis inhibitory factor (OCIF) was isolated from the conditioned medium of human embryonic lung fibroblasts. OCIF is a novel member of the tumor necrosis factor receptor superfamily and identical with Osteoprotegerin (OPG) discovered by the Amgen researchers. Consequently, through the identification of receptor activator of NF-kappaB ligand (RANKL) as a target molecule of OCIF/OPG, it was demonstrated that RANKL is a crucial factor in the differentiation, maturation, and activation of osteoclasts. Discovery of OCIF/OPG and RANKL has broken new ground in the field of bone physiopathology. Moreover, OCIF/OPG not only contributes to the field of basic science but also is anticipated as a novel therapeutic candidate for the treatment of primary and secondary osteoporosis through a series of pre-clinical and clinical studies. Because OCIF/OPG and RANKL have been proven to be involved in the onset and development of many metabolic bone diseases besides osteoporosis, OCIF/OPG is also expected as a therapeutic candidate for the treatment of such bone diseases.

The influence of gadobenate dimeglumine formulation (E7155) on general reproductive performance and fertility in male rats of the Sprague-Dawley strain was assessed in this study. E7155 was administered by intravenous injection at a dosage of 0.3, 1.0, or 2.0 mmol/kg/day to groups of 22 male rats for 13 weeks. Control animals received 0.9% sterile physiological saline throughout the same period. After four weeks of treatment, each male was paired with an untreated female of the same strain. Each male was paired again after 10 weeks of treatment with another untreated female of the same strain. All females were killed on Day 14 of gestation for examination of pregnancy status. No significant toxicological signs associated with systemic exposure to E7155 were observed. There were no effects of treatment with E7155 on body weight gain, food consumption, macroscopic findings, reproductive organ weights and sperm count or sperm motility in male rats. Mating performance after pairing at Weeks 4 and 10 of treatment as well as litter size and number of survival embryos on Day 14 of gestation were not affected by paternal treatment with E7155. From these results, the No Observed Adverse Effect Level (NOAEL) of E7155 was 2.0 mmol/kg/day for general and reproductive toxicity parameters in male rats treated with E7155 and for development in their embryos.

The inhalation therapy is one of the important treatment of bronchial asthma. The effectiveness of the therapy, however, is different depending on the size of particles produced by each inhalation equipment. Therefore, we have tried to clarify the relationship between the size of inhaled particles and the deposition rate in the lung by using different types of equipment. Four different equipments, Nishou, Pari-Boy, Pari-Master and Atom Soniclizer 905 were used. 99mTc-DTPA was dissolved in physiological saline and was inhaled for evaluation of "deposition" rate in the lung. The deposition rates by Nishou, Pari-Boy, Pari-Master and Atom Soniclizer 905 were 10.4 +/- 5.8%, 27.5 +/- 14.5%, 28.5 +/- 6.5%, and 31.1 +/- 6.8%, respectively. Most of 99mTc-DTPA inhaled was observed in oral cavity. The deposition in the lung by Nishou was significantly reduced compared to other three nebulizers. Those three were evaluated as appropriate equipments for the treatment. The average size of particles in an airsol by those three equipments was less than 5 microns. The study suggests that the size of "particles" in an airsol is very important factor for the inhalation therapy.

Transcatheter embolization (TE) using steel coils was performed on three patients with aorto-pulmonary collateral arteries (APCAs). Case #1: In a 13-year-old boy who had undergone corrective surgery for pulmonary atresia with ventricular septal defect (PA with VSD), one APCA was embolized by the TE technique. This resulted in a remarkable improvement in postoperative pulmonary congestion. Case #2: A 13-year-old boy who had previously undergone procedures to correct tetralogy of Fallot (TOF), underwent TE for two APCAs prior to subsequent surgery before for pulmonary stenosis. The procedure abandoned one APCA because of the long narrow origin of the vessel. For the other APCA, TE was unsuccessfully performed due to the displacement of a coil into the peripheral pulmonary artery. Case #3: An 8-year-old girl with PA with VSD underwent TE for three APCAs before corrective surgery. One APCA arising from the abdominal aorta was occluded successfully. The other two were considered too small at the orifice for TE, and were ligated surgically before corrective surgery. TE is a safe and effective method for suitable cases of APCAs. However, caution should be exercised to prevent complications. The selection of appropriate coils and catheters is also important.

We examined factors promoting malignant progression using a weakly malignant variant cell line, ER-1, derived from c-SST-2, a rat mammary carcinoma. ER-1 cells were converted to a highly malignant phenotype (highly tumorigenic, metastatic, invasive in vitro) by the in vitro/in vivo interaction with host cells reactive to foreign body. Epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) produced by host reactive cells, transiently enhanced the tumorigenicity and in vitro invasiveness of ER-1 cells into an endothelial cell monolayer. The host reactive cells also produced oxygen radicals and induced mutations in ER-1 cells. It is speculated that mutations induced by host reactive cells cause cellular diversification, including the emergence of highly malignant variant cells whose growth is selectively promoted by growth factors such as EGF and TGF-beta.

alpha-[(Phenoxyethylamino)propyl]-alpha-(4-methoxyphenyl) acetonitrile derivatives possessing methyl, bromo, nitro, amino or various sulfonamide groups at 3-position on ring A and an alkoxy group on ring B were synthesized. Their alpha-blocking activities were tested. The activity of 5-[1-cyano-4-[[2-(2-ethoxyphenoxy) ethyl]amino]-1-isopropylbutyl]-2-methoxy-benzenesulfonamide (15a) and 5-[1-cyano-4-[[2-(5-fluoro-2-methoxyphenoxy)ethyl] amino]-1-isopropylbutyl]-2-methoxybenzenesulfonamide (15c) was close to that of prazosin, a typical alpha-blocker. Structure-activity relationship of these derivatives is also stated.

I examined the effects of host cells reactive to foreign bodies such as plastic plate or hemostatic spongel on the progression of tumor cells. QR tumor cells spontaneously regressed in normal C57BL/6 mice apparently associated with a reduction in production of PGE2 by the tumor cells. I have observed that such regressor tumor cells are able to grow lethally when implanted in mice after having been attached to plastic plate. The clones which were derived from these plastic plate-derived tumors in normal mice maintained their growth potential when they were injected into other normal mice. Furthermore the arising tumors produce much higher levels of PGE2 than the original QR tumor cells. Interestingly, I could not observe acquisition of tumorigenicity or a higher level of PGE2-production in the clones obtained from the arising tumors which were grown in 10Gy-irradiated mice. Moreover, QR tumor cells are able to grow in mice when they are injected at the site where plastic plate had been implanted about 30 days previously. These results indicate that the restoration of tumorigenicity of QR tumor cells is not only due to attachment to plastic plate, but also mediated by radiation-sensitive host cells reactive to plastic plate which enhance the progression of tumor cells. Similar results are also obtained by coinoculation of QR tumor cells with host reactive cells which had been induced by implantation of hemostatic spongels into the peritoneal cavity of mice. Greater amounts of PGE2-production by QR tumor cells were observed when the tumor cells were cocultured with spongel reactive cells. This PGE2-production was markedly inhibited by the presence of radical scavengers (Catalase, Mannitol, SOD + Catalase) in the coculture medium(ABSTRACT TRUNCATED AT 250 WORDS)

The pupillary disturbances in twenty five neurosyphilitic patients were investigated. Miotic, light-rigid pupils, i.e., Argyll-Robertson pupils were found in only three of these patients. One of three patients showed unilateral Argyll-Robertson pupil. Irregular margins of the iris were associated with these miotic, light-rigid pupils. Abnormal striations of the iris were found in four of eight non-miotic (medium size), light-rigid pupils. Cocaine or ephedrine produced dilatation of two of these pupils, and, following this mydriasis, the pupils were capable of constricting to light. These abnormalities of the iris were not found in slightly light-reactive pupil. The light-rigid pupil induced by long-term administration of neuroleptics and antiparkinson drug in comparison with Argyll-Robertson pupil was also mentioned, and the findings of many authorities who have proposed a peripheral nerve pathogenesis of the Argyll-Robertson syndrome were reviewed.

We investigated the effects of host inflammatory cells on the progression of QR (C57BL/6 mouse) and ER (SHR rat) regressor tumor cells which spontaneously regress in normal syngeneic hosts. We noted an enhanced tumorigenicity of regressor tumor cells after s.c. implantation with attachment to plastic plate, a situation which induces inflammation in normal hosts accompanied by the development of tumors as compared to normal mice injected with regressor tumor cells in suspension in PBS- which spontaneously regressed. We also observed enhanced tumorigenicity of regressor tumor cells injected into the site of the plastic plate which had been previously implanted into the normal host. Regarding these phenomena, we suggest that tumor progression may be induced by host induced inflammatory cells or their products. We also found enhanced tumor progression of QR regressor tumor cells after co-inoculation with inflammatory cells produced by the implantation of hemostatic spongel into the peritoneal cavity of mice. The mechanisms involved in the progression of regressor tumor cells by co-existence with inflammatory cells are thought to be associated with the production of oxygen radicals, tumor cell chemotactic factors, soft agar colony promoting factors and PGE2.

In recent years many investigators have reported the role of the sympathetic nervous system and the catecholamines in the regulation of renin secretion. It has been recently reported that plasma dopamine-beta-hydroxylase (DBH) excreted through the mechanism of the exocytosis with noradrenaline from the sympathetic postganglionic nervous endings is a mirror of the function of the sympathetic nervous system. In this investigation, blood pressure, urinary catecholamine excretion, plasma DBH activity and plasmsa renin activity (RPA) have been determined in normal individuals during the mecholyl test and insulin-induced hypoglycaemia. In the mecholyl test, plasma DBH activity and PRA markedly increased in five males who showed prominent responses of systolic blood pressure to mecholyl (S type) and changed slightly in eight males who showed minimal responses of systolic blood pressure to mecholyl (N type). It showed that there was a significant relationship between the maximal percent increases from their respective control values of plasma DBH activity and those of PRA following mecholyl. In insulin-induced hypoglycaemia, plasma DBH activity, blood pressure and PRA remarkably increased following a large dose of insulin administration (0.15 u/kg). In a dose of 0.1 u/kg, there was no significant increase of plasma DBH activity and blood pressure. PRA singificantly increased but was lower than a large dose of insulin. Also, it showed that their was a significant relationship between maximal percent increases from their respective control values of plasma DBH activity and those of PRA following insulin administration. These data indicate a close correlation between changes in plasma DBH activity and those of PRA during mecholyl and insulin-induced hypoglycaemia and lend additional support to the concept of sympathetic nervous system mechanism of renin secretion.

Acute pandysautonomia and acute autonomic and sensory neuropathy were reviewed with special reference to their clinical entity, pathogenesis and clinical course. Since acute pandysautonomia was primarily described as an entity by Young et al. in 1969, a number of similar cases have been described. The disorder is characterized by severe sympathetic and parasympathetic impairment with relative or complete preservation of somatic motor and sensory functions. Some cases have only shown a cholinergic dysautonomia, while others have displayed a loss of autonomic function together with other impairments of nervous function. In 1980, Colan et al. reported a patient with acute autonomic and sensory neuropathy, manifesting severe sensory impairment and dysautonomia with marked loss of myelinated and unmyelinated fibers. Several other similar cases have appeared in the literature. Four years prior to the Colan et al. report, the author described a case which showed almost the same symptoms. At the present time, it is not clear whether this disorder is a new syndrome that is different from acute pandysautonomia or merely a subtype of it. The causes of the above two syndromes are unknown; however, an immunological disorder similar to the Guillain-Barré syndrome has been suggested. The clinical course is often protracted with slow improvement. However, from the author's experience, a relatively rapid improvement occurs after a single systemic administration of either parasympathomimetic or sympathomimetic agonists. Acute pandysautonomia which includes acute autonomic and sensory neuropathy has recently become more common: A number of similar cases have been reported worldwide, including many areas in Japan.

Five male student cases of wrist-cutting with suicidal intent were reported. They had only one or two wrist-cutting episodes. They are compared to cases with wrist-cutting syndrome reported by Rosenthal et al. Four of the five cases occurred during a period with depressive symptom, and the fifth during a period with hallucinatoric and delusional state. One case was diagnosed as a schizophrenic, another as depressive and the other three had no clear diagnosis. Two of the five cases had one depressive or schizophrenic parent, and two other cases had one suicidal or accidental death of brother or father. Three of the five cases had tried other methods of suicide, drugs, electricity and gas. However, the prognosis of all five cases is good, three graduating and two remaining in the university. The male cases here have only one or two wrist-cutting episodes different from female cases where a larger number of episodes is common. However, it is necessary to remember that diagnosis for both males and females is very difficult and other symptoms are similar.