Mechanism of atrial natriuretic polypeptide and sodium nitroprusside-induced relaxation in guinea-pig tracheal smooth muscle

Atrial natriuretic polypeptide (ANP) is composed of a family of peptides isolated from rat and human atria. In the present study, the relaxant effects of ANP, sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) were investigated in guinea-pig tracheal smooth muscle, and the tissue cyclic GMP and cyclic adenosine monophosphate (AMP) concentrations were measured. ANP, sodium nitroprusside and 8-bromo-cyclic GMP showed relaxant effects on the spontaneous tone in normal Krebs solution (5.9 mmol/l K(+)-2.4 mmol/l Ca++ solution). They diminished relaxant effects on 40 mmol/l K(+)-0.1 mmol/l Ca++ induced contraction, which was approximately the same tension as the spontaneous tone. Sodium nitroprusside and 8-bromo-cyclic GMP diminished less relaxant effects on 40 mmol/l K(+)-2.4 mmol/l Ca++ induced contraction, but ANP showed no relaxation. The tissue cyclic GMP levels following administration of ANP and sodium nitroprusside in normal Krebs solution, in 40 mmol/l K(+)-2.4 mmol/l Ca++ solution, and in 40 mmol/l K(+)-0.1 mmol/l Ca++ solution increased dose-dependently without regard to external Ca++ concentrations, while the tissue cyclic AMP levels did not change. These results suggest that ANP might be a novel potent relaxant in airway smooth muscle and the relaxant effect may be, at least in part, mediated by cyclic GMP. There was a difference in relaxant effects on tracheal smooth muscle between ANP and sodium nitroprusside.     

Surgical treatment of aortic arch aneurysm associated with the aberrant right subclavian artery

A 64-year-old man, who had an aneurysm of aortic arch associated with the aberrant right subclavian artery, was treated successfully. He was pointed out to have an aneurysm of aortic arch three years ago. Three years later angiograms and computed tomography revealed that it became larger compared with the initial finding. He underwent a replacement of the aortic arch using a woven Dacron graft under open distal method. Aberrant subclavian artery was not involved in the aneurysm. But because the left subclavian artery was involved in it, a woven Dacron graft was interposed between the ascending aorta and left subclavian artery. Postoperative course was uneventful and there were no complications.     

Structural determination of geometrical isomers of microcystins LR and RR from cyanobacteria by two-dimensional NMR spectroscopic techniques

A nondestructive method using a combination of three 2D NMR techniques, DQF-COSY (double quantum filter correlation spectroscopy), HMQC (1H-detected multiple quantum coherence), and HMBC (heteronuclear multiple bond correlation), were developed for structural determination of microcystins, toxic heptapeptides produced by cyanobacteria. With this procedure we were able to assign all carbons and protons of microcystins LR (1) and RR (2), thus determining the constituent amino acid sequences. The procedure was also applied to the microcystin-associated nontoxic minor components, which have molecular weights and amino acid compositions similar to those of 1 and 2 and toxicities different from those of 1 and 2. From detailed analysis of these spectra we rapidly deduced that the minor components are geometrical isomers with respect to C-7 of the diene in Adda of the parent toxins. The structures were finally confirmed to be 3 and 4 by ROESY (rotating frame nuclear Overhauser and exchange spectroscopy) technique.     

Surgical treatment of syphilitic ascending aortic aneurysm: a case report

A 67-year-old man with positive serum reaction for syphilis had been followed by cardiologist for his moderate-sized saccular ascending aortic aneurysm and small-sized abdominal aortic aneurysm. Because of his transient ischemic attack probably secondary to the thrombo-embolism of the aneurysm and rapid growing of its size, surgical treatment was recommended. Resection of the saccular aneurysm with patch plasty of the ascending aorta was performed under the cardiopulmonary bypass associated with right side cerebral perfusion. At the time of operation, the mildly dilated ascending aorta and arch with multiple intimal ulceration were noted. Although his postoperative hemodynamic condition was stable, he suffered from multiple cerebral infarction, probably due to embolism migrated from the fragile aortic intima. His neurological condition was improved promptly, trivial hemi-paralysis was remained. The specimen of resected aneurysmal wall revealed syphilitic changes microscopically. We concluded that the extent of the aortic replacement with prosthetic graft should be deceived not only with its external appearance, but also with the changes of its inside.     

Effect of ureteral obstruction on proximal tubular functions of rat kidney

The effect of complete unilateral ureteral obstruction (CUUO) on proximal tubular functions was studied in rats, using the K+-sensitive microelectrode technique and split oil drop method. In the control kidneys peritubular membrane potential (EMperi) and intracellular potassium activity (aKi) were -70.8 +/- 7.0 mV and 81.2 +/- 22.0 mEq/liter (mean +/- SD), respectively. In the CUUO kidneys both EMperi and aKi were progressively reduced with the duration of obstruction. However, in all tubules aKi values were still above the electrochemical equilibrium. In the three days' CUUO kidneys EMperi and aKi were -51.5 +/- 11.7 mV and 53.8 +/- 22.8 mEq/liter, respectively. Rate of fluid absorption (JVL;nl./sec. mm.) across the proximal tubular epithelium from Ringer solution in the control and three days' CUUO kidneys was 0.029 and 0.0065 respectively. In the CUUO kidneys there were wide variations in JVL and EMperi, but there was a clear correlation between these two variables. JVL from choline chloride solution was negligible in both control and CUUO kidneys. From above results, it was suggested that the proximal tubular reabsorption primarily depending on the Na+-K+ pump might be reduced but still working in the CUUO kidney, and thus the proximal tubular reabsorption might take part in preservation of glomerular filtration during the obstruction.     

A case of congenital antithrombin II deficiency with pulmonary infarction

A 48-year-old woman was admitted because of increased bloody sputum. Since she had had a history of repeated thrombotic episodes including venous thrombosis in the lower limbs (21 year old) and pulmonary emboli developing into pulmonary infarction (41 years old), the patient was treated with anti-coagulant therapy using Warfarin for 7 years. Warfarin was discontinued after admission and heparin was administered instead at a relatively low dose of 5,000 units daily, resulting in a considerable diminution of hemoptysis. Unfortunately however, it caused a relapse of active thrombosis associated not only with a significant increase of the product of fibrinolysis (FDP), LDH and GOT but with a concomitant decrease of the platelet count. Hematological examinations concerning coagulation and fibrinolysis remained within a normal range except for the serum concentration of antithrombin III (AT III) and its functional property with regard to the heparin cofactor, which were 8.8 mg/dl and 48%, respectively. Since the findings were consistent with congenital deficiency of AT III, some members of her family were also examined. The concentration of AT III and its activity in the patient's son and her daughter deteriorated in a similar manner, indicating that this was a definite case of congenital deficiency of AT III. The clinical manifestations of 87 cases with congenital AT III deficiency, belonging to 24 families reported in Japan were reviewed.     

Effects of testosterone, and testosterone plus estrogen, in the castrated rat ventral prostate--histopathological and immunocytochemical studies.

The effects of testosterone (T) and 17 beta-estradiol (E2) on the prostate of castrated rats were investigated by histopathological and immunocytochemical procedures. A significant increase in prostatic weight occurred after 6 weeks treatment with T alone and in combination with E2. The greatest increase in prostatic weight occurred after the administration of T plus E2. Histopathologically, glandular hyperplasia of the prostate was noted, and the number of bromodeoxyuridine (BrdU)-positive cells showed a significant increase over that induced by testosterone alone.     

Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin.

Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKC gamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKC gamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC.     

Vasodilator effects of C-type natriuretic peptide on cerebral arterioles in rats

The vasodilator effects of C-type natriuretic peptide (CNP) were investigated in isolated rat cerebral arterioles. CNP caused dose-dependent vasodilation, maximally by 10.0±2.2% at 10⁻⁶ M. The median effective concentration (EC₅₀) was 5.2×10⁻¹⁰ M. In contrast, atrial natriuretic peptide and B-type natriuretic peptide, other members of the natriuretic peptide family, produced little or no vasodilation. Pretreatment with methylene blue (10⁻⁴ M) abolished CNP-induced vasodilation, whereas pretreatment with N^G-monomethyl-

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-arginine or indomethacin did not inhibit vasodilation. Thus, CNP is suggested to cause significant vasodilation in cerebral arterioles via a cyclic guanosine monophosphate-dependent mechanism. © 1997 Elsevier Science B.V. All rights reserved.     

Polyglucosan bodies in the central nervous system of a fox.

Polyglucosan bodies (PGB) in the central nervous system of an old male fox, Vulpes vulpes japonica, without neurological signs were examined by light and electron microscopy, lectin histochemistry and immunohistochemistry. Fox PGB were round, slightly-basophilic and PAS-positive structures. Most of the bodies were situated free in the neuropil. Electron microscopically, fox PGB were composed mainly of branching filaments and electron-dense material. Lectin histochemistry revealed that fox PGB contained mannose and galactose in addition to glucose. Fox PGB were immunoreactive for monoclonal antibodies raised against human polyglucosan. These findings indicate that fox PGB are similar to feline ones.