The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

Hypertonic saline alters electrical barrier of the airway epithelium.

OBJECTIVE: The effect of tonicity changes in nebulizer solutions and irrigations on nasal mucosa is not well known. The present study aims to determine the basic mechanism of hypertonic solution on airway epithelial barrier. STUDY DESIGN AND SETTING: We investigated the electrical potential difference (PD) that is influenced by both active transport and the transepithelial electrical resistance of the epithelial mucosa in the human nose in vivo. The short circuit current (SCC) revealed net ion transport across the epithelium in the guinea pig trachea in vitro. Finally, the size dependency of macromolecules across the tracheal mucosa was determined in vitro using FITC-labeled dextrans of different sizes. RESULTS: PD was significantly decreased after topical application of hypertonic solution both in human and in guinea pig nose. SCC was significantly decreased after application of hypertonic solution. The transport of these dextrans from the basolateral to the apical side was not increased significantly after apical application of hypertonic saline. CONCLUSIONS: Hypertonic saline enhances the electrical permeability of the airway epithelial mucosa but not transport of macromolecule in the short term.     

Presynaptic α2-adrenoceptor-mediated modulation of norepinephrine release from vascular adrenergic neurons in reduced renal mass salt hypertensive rats

The present study was designed to investigate the presynaptic alpha 2-adrenoceptor function to inhibit norepinephrine (NE) release in blood vessels of reduced renal mass salt hypertensive rats (Na-loaded HT). Isolated perfused mesenteric vasculatures were prepared from Na-loaded HT and normotensive control rats (NT-control), and the NE release and vascular responsiveness were examined. Periarterial nerve stimulation caused a significantly greater release of NE and pressor responses in Na-loaded HT than in NT-control. Yohimbine, a potent alpha 2-adrenoceptor antagonist, demonstrated the facilitatory effects on NE release during nerve stimulation. The effects were significantly attenuated in Na-loaded HT compared with NT-control. These results demonstrate that vascular sympathetic nervous activity might be enhanced in Na-loaded HT. Furthermore, the increased NE release from vascular adrenergic neurons in Na-loaded HT could partially depend on impaired presynaptic alpha 2-adrenoceptor-mediated modulation, which might contribute to the pathogenesis and maintenance of this form of salt-dependent hypertension.     

Synergistic effect of 1,25-dihydroxyvitamin D3 and retinoic acid in inducing U937 cell differentiation.

We examined the effects of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), and its synthetic analogue, 22-oxa-1,25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, 1,25-(OH)2D3 did not inhibit cellular growth, but increased CD 14-positive cells. Simultaneous addition of 1,25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD14 expression. With regard to [Ca2+]i, however, 5 days' incubation with either of them increased the basal [Ca2+]i level and induced U937 cells to respond to formyl-methionyl-leucyl-phenylalanine (FMLP). When the cells were incubated with both 10(-6) M RA and 10(-8) M 1,25-(OH)2D3, basal [Ca2+]i was higher and FMLP caused a greater increase in [Ca2+]i than when only RA or 1,25-(OH)2D3 was added. These data suggest that RA and 1,25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. The 22-oxa-1,25-(OH)2D3 induced CD14 expression, basal [Ca2+]i increase and [Ca2+]i response to FMLP, but did not cause cellular growth inhibition in U937 cells, and in these points, 22-oxa-1,25-(OH)2D3 exhibited no significantly different effects from 1,25-(OH)2D3. Thus, 22-oxa-1,25-(OH)2D3 has the same potent activity as 1,25-(OH)2D3 in inducing differentiation of U937 cells.     

Experimental focal cerebral ischemia produced by embolization with silicone cylinder in normotensive (NTR) and spontaneously hypertensive rats (SHR): comparison of neurological and pathological findings

A focal cerebral ischemic model was produced by occlusion of the intracranial main cerebral artery with a silicone cylinder in normotensive (NTR) and spontaneously hypertensive rats (SHR). Main cerebral artery could be successfully occluded in approximately 90%. The most frequent embolized site was the distal part of the internal cerebral artery (ICb) and less frequently the horizontal segment of the anterior cerebral artery (Al). Mortality rate of NTR with ICb occlusion (NTR-ICb) was 43% at 72 hours after embolization and that of SHR with ICb occlusion (SHR-ICb) was 67% at 24 hours after embolization. NTR-ICb showed neurological signs (i.e. circling movement, hemiparesis, poor response to pain stimuli) and histologically, showed infarction in the deep cerebral structures (i.e. thalamus, hypothalamus, hippocampus, and internal capsule) accompanied with mild disruption of blood-brain barrier (BBB). SHR-ICb showed more serious neurological signs and more severe cerebral infarction in the deep cerebral structures with severe disruption of BBB. In SHR-ICb, ischemic cerebral edema was more prominent which may deteriorate symptoms and pathological findings compared to NTR-ICb. This embolization model is proposed to be useful for studying the pathophysiology of focal cerebral ischemia, especially, early ischemic edema.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties

A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma.     

A seromuscular stripping method to create a nipple valve without metal stapling for continent urinary reservoir

Urinary continence with a Kock or Mainz pouch is achieved by a nipple valve of the invaginated ileum which is usually fixed with metal staples. However, metal staples can cause various complications as a foreign body. The seromuscular stripping method, a new technique to create a nipple valve, was applied to 17 patients with bladder cancer in the construction of a continent urinary reservoir by the ileocolonic pouch (Mainz pouch). Metal staples were not used. The results were satisfactory except for 2 patients who became incontinent because of prolapse of the nipple in one and insufficient valve function due to ischemic change of the nipple valve in the other. Histology of the nipple valve from an autopsy case showed a good double layer nipple valve that functioned well to preserve continence.     

Persistent left superior vena cava draining to left atrium with normal coronary sinus

In embryology, a persistent connection of the left superior vena cava to the left atrium rarely coexists with a coronary sinus. We herein report an unusual case of persistent left superior vena cava terminating in a left atrium with normal coronary sinus, which was revealed at the time of permanent pacemaker implantation after a second operation for recurrent left atrioventricular valve regurgitation. Because this anomaly had gone undiagnosed at the first operation, we were unable to diagnose it prior to the second operation, because the preoperative coronary angiogram clearly demonstrated a coronary sinus that was not dilated. We would have repaired the anomaly using a patch or other procedure had it been diagnosed before the second operation in order to prevent cyanosis or brain complications secondary to right-to-left shunting. One should always be on guard for this rare condition.     

A case of traumatic spinal subarachnoid hematoma causing compression of the cauda equina]

A case of traumatic spinal subarachnoid hematoma causing compression of the cauda equina is reported here. The patient, a 76 year-old woman, who had fallen down by accident 1 month before, was admitted to our hospital presenting lumbar pain radiating into her right thigh, monoplegia of the right leg and urinary incontinence. Myelography and metrizamide CT demonstrated a filling defect mimicking intradural extramedullary tumor at the level of L1 and L2. Magnetic resonance imagings (MRI) revealed a subacute or chronic hematoma compressing the conus medullaris and the cauda equina. Operation was performed and an old hematoma, which occupied most of the spinal subarachnoid space and compressed the conus and cauda equina from right to left, was removed. No definite bleeding point was detected and no traumatic change was seen on the cord. Neither tumor nor abnormal vessel was detected. After surgery, the symptoms improved partially. On a review of the literature, we found only 4 cases of traumatic spinal subarachnoid hematoma, all of which occupied the cervical or thoracic portion of the spine. Our case is the first report, except for the cases following lumbar spinal tap, of traumatic spinal subarachnoid hematoma causing compression of the cauda equina. Though usually blood in CSF diffuses immediately, a clot may be formed when a large amount of bleeding obstructs the spinal canal. In our case, furthermore, deformity and narrowing of the spinal canal had preceded for many years, following lumbar vertebral compressed fracture related with osteoporosis. This might have promoted the process of canal obstruction and clot formation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined cisplatin and radiation therapy in patients with invasive bladder cancer

Thirty-five patients with T2–T4 invasive bladder cancer were treated with combined cisplatin and radiation therapy. In 18 patients radical cystectomy was performed after the combined therapy. In the other 17 patients radical cystectomy could not be performed for various reasons. Pathological examination of the cystectomy specimens showed down-staging in 66.7% and no residual tumour in 33.3%. These results suggest a synergistic action of cisplatin and radiation. Side effects were not severe and were well tolerated. This combined therapy of cisplatin and radiation is very effective for invasive bladder cancer.