Regional differences in endothelin converting enzyme activity in rat brain: inhibition by phosphoramidon and EDTA.

1. It has been demonstrated previously that conversion of big endothelin-1 (bET-1) to endothelin-1 (ET-1) is inhibited in vitro and in vivo by phosphoramidon. In addition, ET-1 binding sites and mRNA have been shown within the brain. Here we expand upon our previous observation that rat brain contains phosphoramidon-inhibitable endothelin converting enzyme (ECE) and show that this activity is not uniformly distributed throughout the brain. 2. ECE activity was detected by a bioassay which depended upon the 10,000 fold difference in potency between bET-1 and ET-1 as stimulants of guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in kidney epithelial (PK1) cells of the pig. Data were confirmed by specific enzyme-linked immunosorbent assay (ELISA) employing antibody directed against ET-1/3(17-21). 3. Following homogenization of the whole brain and ultracentrifugation the 100,000 g pellet contained greater than 4 times more ECE activity than the cytosol. Washing of the pellet with KCl (1 M) and extraction with the detergent CHAPS (20 mM) revealed a phosphoramidon-inhibitable ECE within the residual particulate fraction (nominally classified as the cytoskeletal fraction). Phosphoramidon (IC50, approx. 5 microM) or EDTA inhibited the conversion of bET-1 to ET-1 by the cytoskeletal fraction of rat brain by more than 60%.2+ 4. Following dissection of rat brain into olfactory bulb, cerebral cortex, striatum, hippocampus, cerebellum, midbrain (including thalamus), hypothalamus and medulla oblongata (including pons) the greatest ECE was detected in the hypothalamus and medulla oblongata.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway troubles related to the double-lumen endobronchial tube in thoracic surgery

Purpose Several case reports indicate critical respiratory complications in relation to the double-lumen endobronchial tube (DLT). A prospective survey for the airway problems in using the DLT is presented. Methods One hundred adult patients undergoing thoracotomy for lung cancer were investigated. Tube malposition and airway obstruction were searched using a fiber-optic scope. The endobronchial cuff was positioned just below the trachcal carina while the trachea was intubated with a DLT (Rüsch). The distances of displacement, from the tracheal carina to the bronchial cuff, were measured during anesthesia using an epidural catheter, which had marks every 5 mm. The distances for correcting the tube position were measured at both the bronchial cuff and the level of the teethPaO₂,PaCO₂ andSPO₂ were also measured. Results Malposition (displacement over 5 mm from the correct position) was found in 42 patients, and 40 of them were in a withdrawal direction, occurring at the postural change and during one-lung ventilation, especially during manipulation of the lung hilum. Correcting distances at the level of the teeth were 15.3–3-times longer than those at the bronchial cuff. Airway deformities and gradual withdrawal of the bronchial cuff were found in association with surgical manipulation. Obstruction occurred at the tips of the tracheal tube in four patients and the bronchial tube in six patients, and at the tip of both in two patients. Hypoxemia (PaO₂<60 mmHg) occurred in four patients and hypercapnea (PaCO₂>60 mm Hg) in two patients. Conclusion Most of the DLT obstructions were associated with withdrawal malposition. Great attention to DLT displacement and airway deformity is advised.     

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     

Recombinant tumor necrosis factor stimulates interleukin-1 production in glomerular cultures from rats with nephrotoxic serum nephritis

We have investigated the effect of recombinant tumor necrosis factor (r-TNF) on the release of interleukin-1 (IL-1) in glomerular cultures from rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN). Freshly isolated glomeruli from the NTSN rats were incubated for 24 h in the presence of r-TNF. When the glomeruli were activated by r-TNF substantial amounts of IL-1 could be detected in the supernatants as measured by the mouse thymocyte assay. The r-TNF-induced IL-1 activity was significantly higher in rats with NTSN than those in normal controls and the other control group, consisting of preimmunized rats (rabbit IgG), then given normal rabbit globulin instead of NTS. To avoid the effect of prostaglandins on the IL-1 assay, we cultured the glomeruli with addition of indomethacin and assayed IL-1 activity in the culture supernatants. This cyclooxygenase inhibitor augmented r-TNF-induced IL-1 production. Our data suggest that r-TNF can serve as a potent stimulator of IL-1 synthesis in glomerular cultures from rats with NTSN.     

Metabolites of (+)-dehydroabietic acid in rabbits

The seven metabolites of (+)-dehydroabietic acid (DHA) were newly isolated from rabbit urine by liquid chromatography. On the basis of chemical and spectral data their structures were established to be (15S)-8,11.13-abietatrien-16,18-dioic acid, 2 alpha-hydroxy-8,11,13,15-abietatetraen-18-oic acid, (15R)-15,16-dihydroxy-8,11,13-abietatrien-18-oic acid, 2 beta,15-dihydroxy-8,11,13-abietatrien-18-oic acid, (15S)-2 beta,16-dihydroxy-8,11,13-abietatrien-18-oic acid, 2 alpha,15-dihydroxy-8,11,13-abietatrien-18-oic acid, and (15S)-2 alpha,16-dihydroxy-8,11,13-abietatrien-18-oic acid. The possible hydroxylation routes of DHA in rabbits and the difference between the metabolism of DHA in microorganisms and that in rabbits are discussed.     

Dual microcatheter and guidewire snare technique for retrieval of intravascular foreign body: technical note

A transjugular snare technique was used to retrieve a stretched, residual mechanical detachable coil which extended from the cavernous sinus to the femoral vein, obliterating the transpetrosal route for further embolisation. The coil was snared by a microguidewire. Our new technique is described in this paper. Received: 19 April 1995 Accepted: 31 July 1995     

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid,in a patient with cytochrome b positive X-linked chronic granulomatous disease

Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patient's CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patient's cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57.     

Expression of Lewis Y (Ley) Antigen in Human Anagen Hair Follicles

Lewis Y (Le^y) antigen, a difucosylated tetrasaccharide found on type 2 blood group oligosaccharides of glycolipids and glycoproteins, is thought to be a phenotypic marker predictive of cell differentiation. The distribution of this antigen in human anagen hair follicles was examined by immunohistochemical staining using a monoclonal antibody (AH-6) to Le^y. In the bulbar and suprabulbar portion of anagen hair follicles, Le^y antigen was detected in the three layers of the inner root sheath. Subsequently, the positive staining became translocated to the innermost layer of the outer root sheath in the middle part of the hair follicles. In the upper portion of the hair follicles, Le^y antigen was found in the outer cells of the outer root sheath. These findings suggested that the expression of Le^y antigen in the anagen hair follicles was correlated with the processes of keratinization or terminal differentiation.     

Surgical results of performing R4 gastrectomy for gastric cancer located in the upper third of the stomach

Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.