The effect of dexamethasone on human mucin 1 expression and antibody-dependent complement sensitivity in a prostate cancer cell line in vitro and in vivo

Dexamethasone has been shown to up-regulate human mucin 1 (MUC1) expression in certain types of cancer cell lines in vitro, suggesting that this gluocorticoid may enhance MUC1-based immunotherapies. Here we investigated the effect of dexamethasone on MUC1 expression in the DU145 human prostate cancer cell line in terms of antibody-mediated complement-dependent cell lysis. Cells treated with 1 x 10-8 m dexamethasone in vitro expressed maximal levels of MUC1 after 6 days, with an approximately 3-fold increase over MUC1 levels on untreated cells. DU145 cells were highly resistant to lysis by anti-MUC1 antibody and complement, and their susceptibility to antibody and complement was unaffected by dexamethasone treatment. However, dexamethasone also induced expression of the complement inhibitor decay accelerating factor (DAF) on DU145 cells. Blocking or overcoming the function of DAF resulted in enhanced complement-dependent lysis of dexamethasone-treated cells with anti-MUC1 antibodies, indicating that the failure of dexamethasone to enhance the complement susceptibility of DU145 cells was caused by the up-regulated expression of DAF. We also investigated MUC1 expression in vivo and found that MUC1 expression was significantly up-regulated on tumour cells isolated from immune-deficient mice that had been injected with dexamethasone. However, in contrast to in vitro data, there was no difference between the levels of DAF expressed on tumour-derived DU145 cells isolated from either phosphate buffered saline (PBS)-treated or dexamethasone-treated mice, and tumour cells isolated from dexamethasone-treated mice were more sensitive to complement-mediated lysis. In the broad context of immunotherapy, the in vivo data support the use of dexamethasone as an adjunct treatment. Up-regulated DAF expression would not be a favourable outcome of dexamethasone treatment in terms of complement-dependent antibody therapy, but the in vivo data caution against extrapolation of in vitro data with regard to the modulation of complement inhibitors reported here and elsewhere.     

Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases.

A new monoclonal antibody (MoAb) HA58 (IgG1) was prepared, which recognizes the binding site on the intercellular adhesion molecule-1 (ICAM-1) antigen to the lymphocyte function-associated antigen-1 (LFA-1). The double-determinant immunoassay (DDIA) was established with use of MoAb HA58 and another anti-ICAM-1, MoAb CL207, to detect the soluble, shedding ICAM-1 antigen. Human recombinant interferon-gamma (IFN-gamma) induced not only the expression of cell surface ICAM-1, but also the shedding ICAM-1 antigen in an IFN-gamma concentration-dependent and incubation-time-dependent manner. DDIA was applied to detect the shedding ICAM-1 antigen in the sera of patients with malignant or benign diseases. The incidence of positivity for ICAM-1 antigen in malignant diseases was higher than that in benign diseases or in healthy controls. Furthermore, the sera of cancer patients with liver metastasis showed higher levels of the shedding ICAM-1 antigen. These findings suggest that serum ICAM-1 antigen may be a useful marker to monitor tumor burden in cancer patients.     

Correlation between ventricular flow field and valve closing sound of mechanical mitral prostheses

The Jyros (JR) valve and the newer On-X and MIRA valves, all installed antianatomically, were compared with the St. Jude Medical (SJM) valve in the mitral position to study the effects of valve design differences on the down-stream flow field and the associated valve closing sound. The dynamic particle image velocimetry method utilizing a high-speed video flow visualization technique was used to map the velocity field, and wavelet analysis of the sound was used to find the correlation between the ventricular flow field and the valve closing sound. Based on the experimental data, the following general conclusions can be made. In the velocity field directly below the mitral valve, where the distinct characteristic differences of the valve designs will be evident, twin symmetrical circulations were observed due to the divergent nature of the flow generated by the two inclined half-disks with the valve installed in the anti-anatomical orientation; the SJM, the On-X, and the MIRA valves generated a centrally downward circulation that opposed the valve leaflet closing movement, and resulted in relatively loud valve closing sounds.     

Etiological Study of Diarrheal Patients in Vientiane, Lao People’s Democratic Republic

The etiological agents of diarrhea in Vientiane, Lao People’s Democratic Republic (Lao PDR), were studied in the period from October 1996 to August 1997. A total of 880 patients with diarrhea visiting medical facilities were examined for Shigella, Salmonella, diarrheagenic Escherichia coli, Vibrio, Aeromonas, Campylobacter, and rotavirus. Shigella spp., heat-stable enterotoxin (ST)-producing E. coli, and serogroup-based enteropathogenic E. coli were found to be the main organisms causing diarrhea in Vientiane, with frequencies of 16.8% (148 of 880), 17.2% (111 of 645), and 11.0% (97 of 880), respectively. Relatively low incidences were observed in the cases of Salmonella spp., (0.6%; 5 of 880), Campylobacter spp. (4.4%; 39 of 880), and rotavirus (6.1%; 9 of 148), and no isolates of V. cholerae O1 or O139 or Aeromonas were recovered. An analysis of the incidences of enteropathogens with respect to age and seasonal variations demonstrated that the frequencies of isolation of Shigella spp. and heat-labile enterotoxin-producing E. coli were significantly higher in those aged 1 to 5 years than in those younger than 1 year of age and those older than 5 years of age (P < 0.0001 and P < 0.05, respectively) and that the frequencies of isolation of Shigella spp. and ST-producing E. coli were significantly higher in the rainy season than in the dry season (P < 0.005 and P < 0.001, respectively). Almost all strains of Shigella spp. tested were resistant to ampicillin, tetracycline, and erythromycin and were susceptible to cefdinir and ofloxacin. This is the first intensive and longitudinal study to define the etiologic agents of diarrheal diseases in Lao PDR.     

A case of mixed connective tissue disease developed into overlap syndrome of progressive systemic sclerosis, systemic lupus erythematosus, polymyositis and Sj?gren's syndrome

We encountered a patient who developed an overlap syndrome of progressive systemic sclerosis (PSS), systemic lupus erythematosus (SLE), polymyositis (PM) and Sj?gren's syndrome (SjS) while we were treating her for mixed connective tissue disease (MCTD). This 42-year-old woman had been photosensitive since 18 years of age. In 1986, Raynaud's phenomenon, swollen hands and arthralgia appeared; therefore, we started to treat this patient based on a diagnosis of MCTD. At that time, her anti-RNP antibody titer was 82,920, but she was negative to anti-Sm antibody. In 1988, she was admitted to our hospital with chief complaints of aggravation of polyarthralgia and myalgia. On physical examination, she showed difficulty in opening her mouth, systemic dermal sclerosis, a decrease in muscular strength and rales. In laboratory tests, her myogenic enzyme level was increased, and she was found to be positive to LE cells, antinuclear antibody, anti-DNA antibody, anti-ENA antibody and anti-SSA antibody. Furthermore, histological features clearly corresponding to those of PSS were found by skin biopsy, myogenic changes by electromyography, evidence of chronic inflammation of the salivary glands by lip biopsy, and proliferative changes in the mesangium were detected by renal biopsy. The concept of MCTD, especially the differences from overlap syndrome, is vague. Therefore we need further study about many cases. Since there have been no reports on cases having sufficient evidence of the development of the overlap syndrome of PSS, SLE, PM and SjS during a course of MCTD, our patient would provide very useful data contributing to the study of MCTD.     

An electron microscopic study of neurosecretion in the cerebral ganglion of the earthworm

Non-synaptic, exocytotic release of neurosecretory granules in cerebral ganglion neurons was observed electron microscopically in 3 species of the oligochaete annelids Aporrectodea caliginosa, Octolasion cyaneum and Lumbricus terrestris. In addition to the features indicating exocytotic release of neurosecretory granules into perineuronal space, possible features of neurosecretion into blood vessels were seen within the cerebral ganglion. Axon terminals in synaptic contact with perikaryal profiles of cerebral ganglion neurons were also found.     

Significance of fibrils in the formation of the Kimmelstiel-Wilson nodule

Summary The pathogenesis of the nodular lesion in diabetic glomerulosclerosis is described in association with fibrils. Thirteen diabetic patients with glomerular nodular lesions and 9 diabetics without the nodules were examined by electron microscopy using periodic acid-thio-carbohydrazide-silver proteinate staining. In cases of nodular glomerulosclerosis, abundant fibrillar structures mixed with electron-dense material were detected within the nodule and the mesangial matrix. They were also occasionally observed along the subendothelial space of the glomerular capillary walls. On the cross-section, these fibrils, including the lucent periphery, were 34 nm wide. Immunohistologically, collagen V and collagen VI were detected in nodular lesions. In contrast, in cases of the diffuse type of glomerulosclerosis, the widened mesangium was composed of dense material, which resembled the original mesangial matrix. The above fibrils were not detected in the mesangium. These findings suggest that the accumulation of the peculiar fibrils in the glomerular mesangium is a major pathogenic factor in the formation of Kimmelstiel-Wilson nodules.     

Blood flow velocity in the common carotid artery in humans during graded exercise on a treadmill

Cerebral blood volume flow and flow velocity have been reported to increase during dynamic exercise, but whether the two increase in parallel and whether both increases occur as functions of exercise intensity remain unsettled. In this study, blood flow velocity in the common carotid artery was measured using the Doppler ultrasound method in eight healthy male students during graded treadmill exercise. The exercise consisted of stepwise progressive increases and decreases in exercise intensity. The peak intensity corresponded to approximately 85% of maximal oxygen consumption. During this exercise, the heart rate (f _c), mean blood pressure (BP) in the brachial artery and mean blood flow velocity (_cc) in the common carotid artery increased as functions of exercise intensity. At the peak exercise intensity, (f _c), BP and _cc increased by 134.5%, 20.5% and 51.8% over the control levels before exercise (P < 0.01), respectively. The resistance index (RI) and pulsatility index (PI) were determined from the velocity profile and were expected to reflect the distal cerebral blood flow resistance. The RI and PI increased during the graded exercise, but tended to decrease at the highest levels of exercise intensity. As _cc increased with increases in exercise intensity it would be expected that cerebral blood flow would also increase at these higher intensities. It is also suggested that blood flow velocity in the cerebral artery does not proportionately reflect the cerebral blood flow during dynamic exercise, since the cerebral blood flow resistance changes.