Ultrasonographic evaluation of gastric emptying in normal children and children after pyloromyotomy

Gastric emptying in the fundus, body, and antrum of the stomach was evaluated by ultrasonography (US) in 41 control children aged 2 to 18 years and 30 patients aged 1 to 19 years who had undergone pyloromyotomy because of hypertrophic pyloric stenosis. The gastric emptying curve decreased in an exponential manner for both control children and patients, while there was no significant difference in gastric emptying time (GET) between control children and patients within any of the age groups. However, GET was faster for younger children in both groups. An X-ray contrast study of the stomach performed in 2 patients who showed markedly delayed GET showed delayed gastric emptying but no significant deformities of the prepylorus. Our results suggest that US is a reliable method of measuring GET in children.     

Potentiation of Paclitaxel Cytotoxicity by Inostamycin in Human Small Cell Lung Carcinoma, Ms-1 Cells

In the present study, we found that inostamycin increased the ability of paclitaxel to induce apoptosis in Ms-1 cells. A considerably higher concentration of paclitaxel was required for the induction of apoptosis in Ms-1 cells than in other cell lines tested. Treatment of Ms-1 cells with inostamycin, an inhibitor of phosphatidylinositol (PI) synthesis, reduced the dosage of paclitaxel required to induce cell death by apoptosis. This effect of inostamycin is specific to Ms-1 cells, and inostamycin did not increase the cytotoxicity of other antitumor drugs such as adriamycin, vinblastine, methotrexate, cisplatin, etoposide, or camptothecin in Ms-1 cells. Addition of inostamycin to paclitaxel-treated cells caused a significant increase in the sub G1 peak, representing apoptosis, which was accompanied by a decrease in the G2/M peak seen in paclitaxel-treated Ms-1 cells, without affecting paclitaxel-inhibited tubulin depolymerization. Moreover, paclitaxel did not enhance inostamycin-inhibited PI synthesis. The expression levels of Bcl-2, Bax, and Bcl-X_L were not changed following the co-treatment with inostamycin plus paclitaxel, whereas the activated form of caspase-3 was markedly increased. Thus, inostamycin is a chemosensitizer of paclitaxel in small cell lung carcinoma Ms-1 cells.     

Afferents of cranial sensory ganglia pathfind to their target independent of the site of entry into the hindbrain

In vertebrates, sensory neurons interconnect a variety of peripheral tissues and central targets, conveying sensory information from different types of sensory receptors to appropriate second-order neurons in the central nervous system (CNS). To explore the possibility that the different rhombomere environments where sensory neurons enter into the hindbrain affect the pathfinding capability of growth cones, we studied the development of the VIIIth ganglion afferent both in vivo and in vitro. We focused on the vestibular nerve because it is the only cranial nerve projecting to the cerebellum, allowing for ready identification from its pattern of projection. Embryonic rat brain was cut along the dorsal midline and, with the VIIIth and Vth ganglia still attached, flat mounted and visualized with antibodies specific for sensory ganglia. Axons reached the cerebellar primordium at embryonic day (E) 13, then splayed out towards the edges of the rhombic lip of rostral hindbrain. In vitro, the VIIIth ganglion showed development similar to that in vivo and innervated the cerebellum, an appropriate target, indicating that mechanisms for axon guidance and target recognition are preserved in vitro. When the VIIIth ganglion was transplanted to the position of the Vth ganglion, axons from the transplanted ganglion entered the cerebellar primordium with a trajectory characteristic of the VIIIth nerve. These results indicate that the central projection pattern of the VIIIth nerve is not affected by the environment of nerve entry into the brainstem, suggesting that axons of sensory cranial ganglion intrinsically possess the capacity to find their target correctly.     

Bone fracture receiving LH-RH agonists for prostatic cancer

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers. RESULTS: The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.     

Calpain inhibitor inhibits secretory granule maturation and secretion of GH

Clathrin- and AP-1-coated buds are present on immature secretory granules of endocrine cells that mature into clathrin-uncoated granules. The mechanism of clathrin and adaptor protein uncoating has remained obscure. Benzyloxycarbonyl-L-leucyl-L-leucinal (ZLLal), a calpain inhibitor, reduced growth hormone (GH) secretion with intracellular accumulation, in a GH-secreting rat pituitary tumor cell. Pulse and chase demonstrated that ZLLal retarded the turnover of clathrin (Clt.H) and adaptins. ZLLal-treatment co-immunoprecipitated the increased amounts of GH with Clt.H and adaptins compared to control cells, suggesting the intracellular accumulation of immature secretory granules. Clt.H and adaptins were limited-proteolyzed by m-calpain in vitro, indicating that calpain may be involved partly in the maturation of secretory granules in endocrine cells via the process of clathrin uncoating.     

Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) is a Mediator of Multiple Physiological and Pathological Pathways

Thrombospondin-1 (TSP-1) is believed to be an endogenous angiogenic inhibitor. In this study, we report that a single 1 h bout of treadmill running increases TSP-1 mRNA 3–4-fold (p < 0.001). Interestingly, with short-term training (up to 5 days, 1 h/day) the acute response of TSP-1 mRNA to exercise was ablated after 3 days. Following long-term training (8 weeks, 1 h/day, 5 d/wk), in either normoxia or chronic hypoxia, the TSP-1 mRNA response to an acute bout of exercise was restored and increased 3–4-fold (p < 0.01). However, chronic exposure to hypoxia (8-weeks) decreases both the basal and acute exercise-induced TSP-1 mRNA levels by 44 and 48%, respectively (p < 0.05). Based on the robust TSP-1 gene response to a single acute exercise bout, its temporal response to repetitive exercise bouts, and the putative role of TSP-1 in the angiogenic process, we speculate that TSP-1 may play a role in regulating the onset of skeletal muscle angiogenesis in response to exercise.     

Long‐term efficacy of psoriasis vulgaris treatments: Analysis of treatment with topical corticosteroid and/or vitamin D3 analog,oral cyclosporin,etretinate and phototherapy over a 35‐year period, 1975–2010

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side‐effects and cost. It is necessary to evaluate the effect of long‐term psoriasis treatment, but there have been no reports evaluating long‐term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long‐term treatment with a combination of topical corticosteroid and topical vitamin D₃ analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.