Aneurysm of the ductus diverticulum in adults The diagnostic value of three-dimensional computed tomographic scanning

Ductus arteriosus aneurysm is rare in adults and preoperative diagnosis has not been usually done. We report 2 cases of adult type ductus arteriosus aneurysm. In both cases, 3D computed tomographic scanning showed a saccular aneurysm originating from the distal aortic arch toward the left pulmonary artery, which had a notching in the orifice of the aortic side. They were successfully treated surgically though one was a ruptured aneurysm to the left pulmonary artery. In these cases, 3D-CT scan was of great value in the preoperative diagnosis of the ductus arteriosus aneurysm.     

Enhanced effect of intra-arterial adriamycin administration in combination with degradable starch microspheres on an intra-arterial chemotherapy model of nude rats transplanted of human gastric cancer

Enhancement of the antitumor effects of adriamycin (ADR) by concomitant use of degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM was investigated. An intra-arterial chemotherapy model of the nude rats transplanted of human gastric cancer xenografts (H-154) in the hind-limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. In the pharmacological study, increase of regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. DSM 30 mg/kg, which caused temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth. ADR 3 mg/kg mixed with DSM 30 mg/kg was more effective than ADR 3 mg/kg solution. Furthermore, mixture of ADR 2 mg/kg and DSM 30 mg/kg had a greater effect on tumor growth than ADR 2 mg/kg following DSM 30 mg/kg. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR have contributed to such a strong effect of ADR mixed with DSM.     

Effects of Glucocorticoids on Humoral and Cellular Immunity and on Airway Inflammation in Patients with Steroid-Dependent Intractable Asthma

The effects of glucocorticoids on the proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid in relation to humoral and cellular immunity were studied in 56 patients with steroid-dependent intractable asthma. To analyze the mechanism responsible for reduced numbers of BAL lymphocytes, we divided the subjects into 4 groups according to their BAL lymphocyte proportions: 0—4.9%, 5.0-9.9%, 10.0-14.9%, and 15.0-20.0%. Serum IgG levels and the peripheral lymphocyte count were significantly reduced in patients with a low proportion of BAL lymphocytes (less than 9.9%) than in those with more than 10% BAL lymphocytes. Delayed cutaneous reactivity to purified protein derivative was suppressed in patients with a low proportion of BAL lymphocytes (less than 4.9%). The mean proportion of BAL neutrophils tended to increase as the proportion of BAL lymphocytes decreased. These results show that the reduction in BAL lymphocytes produced by glucocorticoids is associated with suppressed humoral and cellular immunity, and that under such conditions the proportion of BAL neutrophils increases.     

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead

Summary A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALAU-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 ± 22 g/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-UCL level (0.83 ± 0.14 and 2.4 ± 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 ± 22 g/l Pb-B (P < 0.05, n = 26), while that of ALA-UCL was observed at 245 ± 30 g/l Pb-B (P < 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 g/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALAU-CL above the cut-off point (3.5 mg/g creatinine). The maximum responses for the two sets of corrected ALA-U levels were both observed at 625 ± 25 g/l. The corrected ALA-U level by HPLC method seems to be a useful indicator for biological monitoring of exposure to lead at low levels (< 400 g/l Pb-B = health-based biological limit, WHO) as well as high ones.     

Renal and hormonal effects of alpha1-adrenoceptor blockade by bunazosin in essential hypertension

Summary The renal and hormonal effects of the ₁-adrenoceptor blocker bunazosin were examined in 6 patients with essential hypertension. Oral bunazosin for 4 to 12 weeks significantly decreased mean blood pressure by 10%, increased effective renal blood flow and creatinine clearance by 34% and 37%, respectively, the plasma norepinephrine concentration was elevated by 60%, and the plasma atrial natriuretic peptide level was lowered by 22%. The plasma renin activity and aldosterone concentration were unchanged. Thus, a moderate reduction in blood pressure was produced by bunazosin treatment while maintaining renal perfusion.     

Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes

Summary Effects of verapamil on the acetylcholine (ACh)-induced K⁺ current were examined in single atrial cells, using the tight-seal whole-cell clamp technique. The pipette solution contained guanosine-5-triphosphate (GTP) or guanosine-5-O-(3-thiotriphosphate) (GTP-S, a non-hydrolysable GTP analogue). In GTP-loaded cells, ACh induced a specific K⁺ current, which is known to be mediated by pertussis toxin-sensitive GTP-binding (G) proteins. Verapamil (0.1–100 M) depressed the ACh-induced K⁺ current in a concentration-dependent fashion. In GTP-S-loaded cells, the K⁺ current remained persistently after wash-out of ACh, probably due to irreversible activation of G proteins by GTP-S. Verapamil (0.1–100 M) also depressed the intracellular GTP-S-induced K⁺ current. However, the magnitude of verapamil-depression of the K⁺ current in GTP-S-loaded cells was significantly smaller than that in GTP-loaded cells at concentrations between 1 and 10 M of the drug. From these results, it is suggested that verapamil may block not only the function of muscarinic ACh receptors but also of G proteins and/or the K⁺ channel itself and thereby depress the ACh-induced K⁺ current in isolated atrial myocytes.Supported by grants from the Ministry of Education, Science and Culture of Japan and the Research Program on Ca Signal Control Send offprint requests to Y. Kurachi at the above address     

FARP2 triggers signals for Sema3A-mediated axonal repulsion

Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant for axons by activating a receptor complex comprising neuropilin-1 as the ligand-binding subunit and plexin-A1 as the signal-transducing subunit. How the signals downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is unknown. Here we show that, in the presence of neuropilin-1, the FERM domain-containing guanine nucleotide exchange factor (GEF) FARP2 associates directly with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2 from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1 recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These activities are required for Sema3A-mediated repulsion of outgrowing axons and suppression of neuronal adhesion. We therefore conclude that FARP2 is a key molecule involved in the response of neuronal growth cones to class-3 semaphorins.     

Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice

Most gastric mucosa-associated lymphoid tissue (MALT) lymphomas are caused by Helicobacter pylori (H. pylori) infection. We previously reported that acquired lymphoid follicles with germinal centers were induced by H. pylori infection in neonatally thymectomized (nTx) mice. In the present study, we developed gastric MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day after birth. At 6 weeks of age, mice were orally infected with 10(8) H. pylori and serially killed 2, 4, 6, and 12 months later. Normal BALB/c and noninfected nTx mice served as controls. Follicle formation occurred after 2 months of H. pylori infection in the nTx mice. Follicle formation and infiltration of intraepithelial lymphocytes progressed in a time-dependent manner. Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also occurred in a time-dependent manner (100% at 12 months). Serum immunoelectrophoresis revealed a monoclonal band (M-protein) in 30% (3/10) of mice 6 months after infection. M-protein-positive mice had amplification of one or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as determined with polymerase chain reaction, suggesting mono- or oligoclonality. Overexpression of Bcl-X(L) protein was immunohistologically observed in the infiltrating B lymphocytes and in some follicular B lymphocytes in 80% (8/10) of the cases at 12 months. Thus, H. pylori infection is involved in the development of gastric MALT lymphoma-like lesions in nTx mice. Our mouse model is useful for clarifying the pathogenetic mechanism of gastric MALT lymphoma by H. pylori infection.