Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia

Objective Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p<0.05). On the other hand, the median survival period after hospital admission due to dysphagia of these 7 patients was longer than that of 17 patients with radiotherapy only before EMS placement, although, the difference was not significant. Conclusion: EMS with an antireflux mechanism is not commercially available in Japan and approval is urgently required. The indication of radiotherapy associated with EMS placement is to be studied further.     

Influence of ouabain on the tracheal musculature of the dog

The effects of ouabain on the smooth muscles of the airway were investigated in anesthetized, paralyzed and artificially ventilated mongrel dogs. Ouabain (30 micrograms/kg, i.v.) caused a constriction of the tracheal smooth muscle which was followed by bradycardia. When ouabain was infused at a rate of 2 micrograms/kg/min (i.v.), the tracheal constriction was induced by a total dose of 45.0 +/- 5.5 micrograms/kg, while the bradycardia appeared with a total dose of 54.4 +/- 6.1 micrograms/kg. The ouabain-induced tracheal constriction was inhibited by bilateral vagotomy. The tracheal constriction induced by i.a. infusion of 10 microM ouabain into the bilateral cranial thyroid arteries was inhibited by bilateral vagotomy, but it was not completely blocked. With bilateral vagotomy, the tracheal constriction induced by i.a. infusion of ouabain was unaffected by 3 microM hexamethonium, but it was significantly inhibited by 1 microM atropine. These results suggest that ouabain may induce tracheal constriction by a neurogenic action in addition to its action via the augmentation of the vagal reflex, and the neurogenic action of ouabain may be related, in large part, to the release of acetylcholine from the presynapses of vagus nerves in dogs.     

An estimation of a model explaining the mechanism causing neurotic disorders using a theory of fuzzy sets

Constructing and estimating a model to explain the mechanism of neurotic disorders is important and significant. The model helps the rearrangement or representation of knowledge obtained from professional physicians. However, it is a very difficult problem, because the objects requiring analysis are mental activities of human beings, and they originally include a comparatively large variance between individuals. The object data were obtained from patients with neurotic disorders who were diagnosed by several doctors for 10 years in a subagricultural areas in Japan. We analyzed the data and calculated the weights attached for personal information depending upon the similarity between the information and the kinds of neurotic disorders using the theory of fuzzy sets. From the results of our analysis, we constructed and estimated a model explaining the mechanism causing neurotic disorders as several linear equations. From data processing points of view, the estimation we attempted is placed in a kind of effective data compression with respect to discrete statistical data.     

Warning against the indiscriminate use of a biological half-time model in deriving the critical concentration of metals

For heavy metals, many studies obtained short biological half-times (BHTs) by administrations of heavy metals. Tsuchiya and Sugita, however, first reported the possibility of a long BHT for cadmium (Cd) calculated from Cd accumulations in postmortem human organs and tissues by age using a non-linear regression method employing a differential equation. According to their reports, the Cd BHTs (point estimators) were 12.1-22.7 years by sex, renal cortex and medulla. The minimums and the maximums of the Cd BHTs on the 95% confidence regions of estimators were 6.9-70.2 years by sex and kidney part. It is presumed that the range of the 95% confidence region for the individual BHTs of renal Cd exists in a range from a few years to at least 100 years because of large individual variations in exposure, absorption rate and excretion rate. Point estimators of BHTs, however, include the assumption that all subjects have been exposed to the same level of Cd at the same year of age over a period of decades and have equal absorption and excretion rates of Cd. Therefore, it is not adequate to calculate a safety level for Cd in the industrial environment or foodstuffs using a value of Cd BHT (point estimator) based on Cd accumulation applying a mathematical model. BHTs of metals require careful evaluation and must not be used indiscriminately to derive a critical concentration, for example, using a mathematical model.     

A successful surgical case of aortic arch aneurysm associated with aortic regurgitation

A 57-year-old male patient with aortic regurgitation and aneurysm of the ascending aorta and the aortic arch underwent aortic valve replacement and graft replacement from the ascending aorta to the aortic arch. The operation was done using cardio-pulmonary bypass and selective cerebral perfusion with deep hypothermia. Postoperative DSA revealed no dilatation of the sinus Valsalva and a good configuration of the anastomosis. It seems that selective cerebral perfusion with deep hypothermia is a safe method to prevent cerebral damage in a case of arch aneurysm.     

Zinc in breast milk during prolonged lactation: comparison between the UK and the Gambia

A total of 580 breast milk samples were collected from 56 lactating women living in a rural village community in The Gambia, West Africa, and 92 samples were obtained from 57 lactating women living in Cambridge, England. Total zinc content of each sample was measured by atomic absorption spectrometry, and pooled samples of the Gambian breast milks, representing successive periods of lactation, were fractionated into fat, whey and insoluble casein fractions, to examine zinc distribution. The two sets of milks both exhibited a dramatic decline in total zinc concentrations with increasing duration of lactation, in common with previous studies. However, the UK milks unexpectedly had lower zinc contents at all stages than the Gambian milks. Milk zinc levels were not significantly related to either maternal age or parity in the Gambian women. The proportion of zinc found in the sedimentable fraction remained nearly constant with increasing duration of lactation, but the proportion found in the fat fraction increased and the proportion in the whey fraction declined. These observations are potentially relevant for estimations of milk zinc availability and the fulfillment of zinc requirements by infants, and hence for infant feeding practices.     

Liquid crystal thermography; a reliable method for detecting soda lime exhaustion

The dynamic and functional state of soda lime can be more precisely assessed by measuring changes in wall temperatures of the absorption chambers rather than observing color change of the soda lime granules. We demonstrated in this report that the liquid crystal thermometer is an inexpensive and reliable measuring device for this purpose.     

A novel murine model of pharyngeal candidiasis with local symptoms characteristic of pharyngeal thrush produced by using an inhaled corticosteroid.

We established a novel murine model of pharyngeal candidiasis maintaining stable yeast population and local symptoms characteristic of pharyngeal thrush. The persistent Candida-infection was prolonged by inhalation of beclomethasone dipropionate corticosteroid. The severity of infection lesions was evaluated by determining viable cell number of Candia albicans and scores representing symptomatic curd-like white patch on pharyngeal tissue. The utility of this model was shown by the disappearance of lesions and fungal cells after treatment with fluconazole (FLCZ). The model would be useful for evaluating new chemotherapeutic or immunotherapeutic approaches against pharyngeal candidiasis, as well as in pathological studies.