Migration of keratinocytes is impaired on glycated collagen I

Advanced glycation end products are the chemical modification of proteins induced by sugars in a hyperglycemic condition. Extracellular matrix proteins are prominent targets of nonenzymatic glycation because of their slow turnover rates. The aim of this study was to investigate the influence of nonenzymatic glycation of type I collagen on the migration of keratinocytes. The migration of keratinocytes was dramatically promoted on native type I collagen-coated dishes compared with that on uncoated dishes. When type I collagen was glycated with glycolaldehyde, large amounts of advanced glycation end products were produced; the glycated collagen I-coated dishes did not promote the migration of keratinocytes. Glycated collagen I did not affect the proliferative capacity of keratinocytes. However, the adhesion of keratinocytes to glycated collagen I was profoundly diminished in a glycation intensity-dependent manner. alpha2beta1 integrin is responsible for the migration and adhesion of keratinocytes to type I collagen. Pretreatment with glycated collagen I did not affect the expression level or functional activity of alpha2beta1 integrin on keratinocytes. These findings suggest that in the presence of glycated collagen I, keratinocytes lose their adhesive and migratory abilities. As the glycation did not modify the alpha2beta1 integrin on keratinocytes, it is suggested that glycation may diminish the binding capacity of type I collagen.     

Progressive supranuclear palsy with asymmetric lesions in the thalamus and cerebellum,with special reference to the unilateral predominance of many torpedoes

This report concerns a notable case of progressive supranuclear palsy exhibiting asymmetric dentate nucleus and thalamic degeneration with numerous torpedoes. The neuronal loss in the ventral lateral nucleus of the thalamus was predominant on the right side, while in the cerebellum, a quantitative study revealed the contralateral predominance of the neuronal loss in the dentate nuclei and torpedo formation, with preserved Purkinje cells. The abnormal tau-protein-related profiles in the two nuclei did not show any laterality in their distribution, indicating that the dentatothalamic tract may have been affected in a non-specific way in this case. In addition, the fact that the prominent sites of torpedo formation and loss of dentate nucleus neurons are identical supports the hypothesis that the torpedoes may be formed in association with neuronal loss in the dentate nucleus because of a plausible metabolic change in Purkinje cells through synaptic detachment of their axon terminals. Received: 4 January 1996 / Revised: 27 March 1996 / Accepted: 5 April 1996     

Intensification of labelings of the immunogold silver staining method by gold toning.

We evaluated the applicability of the gold toning procedure to the immunogold silver staining method using monoclonal antibody against dopamine. Immunolabeling was examined in the rat substantia nigra at light and electron microscopic levels. Vibratome sections of fixed midbrains were incubated with anti-dopamine antiserum and then with 5 nm colloidal gold bound to goat anti-mouse immunoglobulin. Silver staining of these sections produced a light brown immunolabeling. After the sections were processed by gold toning, the labeling became intense black. At a light microscopic level, these high contrast signals were retained after the sections were osmicated and embedded in Epon. At an electron microscopic level, signal-to-noise ratio was high, and the positive staining could easily be verified at a low-power magnification. The technique described here, the gold-toned immunogold silver staining method, provides high contrast signals and is much more sensitive than immunogold silver staining alone. This method, therefore, has great potential for use in immunohistochemical analysis of the central nervous system.     

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Endoscopic sphincterotomy for common bile duct stones: Impact of recent technical advances

Technical improvements, such as mechanical lithotripsy, stenting or nasobiliary drainage, and wire-guided cannulation, have reduced the risk of complications in endoscopic sphincterotomy. To determine the extent of this reduction in risk, we assessed the medical records of 1352 patients with common bile duct stones in whom the procedure was conducted. Complications examined were: acute cholangitis and pancreatitis. Stone clearance was achieved in 1256 patients (92.8%), with an overall morbidity rate of 7.7% and a mortality rate of 0.15%. One hundred and forty-two patients had stones with a diameter greater than 20mm; 97 of these patients did not undergo lithotripsy. Cholangitis occurred in 10 of these 97 patients (10.3%), whereas, in the 45 patients who underwent lithotripsy, there were no cases of cholangitis (P=0.02). Stone removal was not immediately accomplished or attempted in 396 patients. In 82 of these patients in whom a stent or a nasobiliary drain was placed in the common bile duct, the incidence of cholangitis was 1.2%, significantly less (P=0.045) than the incidence of 6.4% in the other 314 patients given no stenting or nasobiliary drain. To overcome difficult cannulation, precut sphincterotomy was conducted in 134 patients and wireguided sphincterotomy, a recently introduced procedure, was conducted in 55 patients. When the precutting technique was used, the incidence of acute pancreatitis was significantly higher (8/134; 6.0%) than that in the patients in whom the standard procedure was conducted, i.e., neither the precut technique nor wire-guided ES was used (23/1218; 1.9%) (P=0.008). There were no cases of pancreatitis in the 55 patients in whom wire-guided sphincterotomy was performed, although the difference was not statistically significant because of the small number of patients (P=0.06). Based on these findings, we conclude that improved technologies have led to a significant reduction of complications in endoscopic sphincterotomy.     

Acute myocardial injury and repeated angina pectoris-like attacks in a young patient with Churg-Strauss syndrome]

A 23-year-old male with bronchial asthma developed eosinophilia (eosinophils greater than 2,000/mm3) and was observed at our hospital. After using a prescribed indomethacin suppository for fever at home, he experienced an attack of acute chest pain and severe dyspnea. He suffered cardiac arrest while being transferred to the ward. After resuscitation, he was diagnosed as having acute myocardial infarction on the basis of electrocardiographic and ultrasonic cardiographic findings, and marked elevation of serum concentrations of myocardial enzymes. Thereafter, he often complained of precordial pain and abdominal pain. When he was administered an analgesic in another hospital, he developed severe precordial pain, and marked ST elevation was recorded on the electrocardiogram. Coronary angiography revealed no stenosis nor atherosclerotic changes, suggesting that severe spasm of the coronary arteries and direct myocardial injury by eosinophils were the causes of the myocardial infarction-like symptoms and angina pectoris-like attacks. He was diagnosed as having Churg-Strauss syndrome (allergic granulomatous angiitis) on the basis of the clinical findings; skin biopsy and transbronchial lung biopsy findings were consistent with the diagnosis. Following steroid administration, his angina-like attacks and abdominal pain ceased. This patient developed two episodes of acute cardiovascular symptoms upon administration of antipyretic analgesics. This suggests that in cases of Churg-Strauss syndrome with aspirin-induced asthma, physicians must be aware of the cardiovascular complications, and such drugs should be administered with caution.     

Noninvasive Nasal Mask BiPAP Management for Prolonged Respiratory Failure Following Cardiovascular Surgery

A bstract The purpose of this study was to assess the efficacy of nasal mask bi-level positive airway pressure (BiPAP) support in managing respiratory failure following cardiovascular surgery. A total of 20 patients requiring postoperative prolonged respiratory support of 72 hours or longer were studied. BiPAP support was used for eight patients (BiPAP group); the other 12 patients were managed using ordinary oxygen mask treatment (control group). The mean age of the BiPAP group and control group was 65 and 58 years of age, respectively. The mean period of postoperative endotracheal intubation of the BiPAP group and control group was 12 ± 5 days and 7 ± 1 days, respectively. Reintubation was necessary in two patients of the control group. The BiPAP group patients required no reintubation. BiPAP support was discontinued within 48 hours in 6 out of 8 patients. The respiratory rates of control group increased (p < 0.1) 24 hours after extubation, however, the respiratory rates of the BiPAP group remained unchanged. The values of the respiratory index of the BiPAP group improved significantly (p < 0.01) after BiPAP management (from 1.5 ± 0.2 to 0.9 ± 0.2). The values of the control group, however, remained unchanged. A-aDO₂ and Qs/Qt decreased (p < 0.1) in the BiPAP group. There were no significant differences in central venous pressure or circulatory status between the two groups. In conclusion, BiPAP support is a noninvasive management technique for postoperative respiratory failure and may also prevent prolonged endotracheal intubation.