Renal aminopyrine demethylation in several species determined by a sensitive radiometric method

Renal microsomal aminopyrine demethylation activities of several species were measured by a sensitive radiometric method using [dimethylamino-¹⁴C-]aminopyrine as a substrate and 2,4-dinitrophenylhydrazine as a trapping agent for the formaldehyde formed. The activity was highest in hamsters (0·75 nmol min⁻¹ mg⁻¹ protein) and that in rabbits, rats, mice, and guinea-pigs was 19·7, 7·0, 4·5 and 3·7%, respectively, of the hamster values. These species differences did not correlate with species differences in cytochrome P-450 content or in NADPH cytochrome c reductase activity. Aminopyrine demethylation activities in sliced renal tissues of several species were also compared. This activity was also found highest in hamsters (0·54 nmol min⁻¹ g⁻¹ wet tissue) and the activities in rabbits, rats, and guinea-pigs were 9·2, 1·8 and 2·5%, respectively, of the hamster values.     

Role of Na+-H+ Exchange on Reperfusion Related Myocardial Injury and Arrhythmias in an Open-Chest Swine Model

The inhibition of Na⁺-H⁺ exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrhythmias and additional cell necrosis. Inhibition of intracellular Ca²⁺ overload via NHE inhibition has been suggested as a mechanism of these protective effects. The aim of this study was to examine whether treatment with amiloride analogues reduces the incidence of reperfusion arrhythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30-minute left anterior descending artery (LAD) occlusion and 180 minutes of reperfusion during atrial pacing at 150 ppm. Intravenous 5-(N,N-dimethyI)-amiloride (AML, 5 μg/kg per min) was administered in the treatment group (n = 7) and intravenous saline in the control group (n = 7), starting 10 minutes before coronary occlusion. The infusion was continued during ischemia and reperfusion. The area at risk was defined by monastral blue dye and infarct size by triphenyltetrazolium chloride staining. Limb leads ECG and monophasic action potentials (MAPs) from the epicardium in the ischemic area were recorded. There was no significant difference in the size of the area at risk and hemodynamic parameters between the groups. However, the infarcted area was 0.4%± 1.0% of the area at risk in the treatment group, whereas it was 62%± 29% in the control group (P < 0.05). Pathological examination (Hematoxylin-eosin and mallory s phosphotungstic acid-hematoxylin staining) revealed that all of the infarcted area consisted of contraction band necrosis. MAP duration in both groups was significantly shortened during ischemia. After reperfusion, MAP duration in the treatment group recovered earlier than that of control group. However, there was no significant difference in the incidence of ventricular tachyarrhythmia between the groups. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model, but did not reduce the incidence of ventricular tachyarrhythmia.     

Distribution of anti-p80-coilin autoantibody in collagen diseaseand various skin diseases

Anti-p80-coilin antibody produces a unique pattern of immunofluorescence staining called nuclear dots characterized by the presence of up to six discrete nuclear bodis in interphase cell nuclei. The distribution of this antibody and its clinical relevance have not been established. We studied the prevalence of anti-p80-coilin antibody in the sera from 810 patients with collagen diseases and various skin diseases. Five sera showed the nuclear dot pattern by indirect immunofluorescence on an HEp-2 cell substrate, and reacted by immunoblotting with 80-kDa protein in a nuclear extract from HeLa cells. Four of these sera were from patients with localized scleroderma, and the other was from a patient with primary Raynaud's phenomenon. The patients with localized scleroderma who were positive for anti-p80-colin antibody had all been classified as having linear scleroderma. They had only one or two lesions, and were negative for antihistone and anti-single-stranded DNA antibodies. Our data indicate that anti-p80-colin antibody is uncommon in skin diseases: however, this antibody is present in patients with a milder form of liner scleroderma, although the incidence of positivity may not be high.     

Japanese Registry of Neuroendovascular Therapy: Extracranial Steno-occlusive Diseases except for Internal Carotid Artery Stenosis

Although utilization of endovascular treatment of extracranial steno-occlusive lesions except for internal carotid artery stenosis continues to increase, there is no consensus regarding the natural course and standard treatment of these lesions. The aim of this study was to characterize the utility of endovascular treatment for extracranial steno-occlusive lesions except for internal carotid artery stenosis. A total of 1249 procedures for extracranial steno-occlusive lesions were identified from the Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET2. Excluding the cases of carotid lesions (290 cases), endovascular procedures were performed for 471 (37.7%) subclavian artery stenoses, 404 (32.3%) extracranial vertebral artery stenoses, and 38 (3.0%) innominate artery stenoses with a technical success rate of 97.2%. A stent was placed for 783 lesions and percutaneous transluminal angioplasty was performed for 183 lesions. Forty complications were reported in this cohort. Among these, ischemic complications were the most frequent (12 cases). Comparison between JR-NET1 and JR-NET2 demonstrated a marked increase in the number of procedures, a change in the utilization of antiplatelet therapy, and an increased rate of favorable outcome. We conclude that the endovascular treatment for extracranial steno-occlusive lesions is relatively safe. Continuous efforts should be made to reduce the complication rate, and further trials are needed to validate the beneficial effect of this procedure.     

Branch Fusion Between the Ventral and Dorsal Pancreatic Duct

Abstract : Fusion of the dorsal and ventral pancreatic ducts exhibits various forms and one of them is branching fusion. Branch fusion was divided into 3 types according to ERP findings. Fusion of the upper branches of the ventral pancreatic duct with the dorsal pancreatic ducts was designated as being type 1. Fusion of the lower branch of the dorsal pancreatic duct with the ventral pancreatic duct in roundabout way was designated as being type 2. Fusion of the lower branch of the dorsal pancreatic duct with the ventral pancreatic duct in short way was designated as being type 3. We demonstrated the presence of branch fusion involving the branch of the dorsal pancreatic duct by histopathological examination and immunohistochemical examination using pancreatic polypeptide cells as an indicator in one patient with type 1 branch fusion and one with type 3 branch fusion who underwent a pancreatoduodenectomy. ERP showed chronic pancreatitis in 3 of 4 patients with type 1, 3 of 8 patients with type 2, and 7 of 18 patients with type 3 branch fusion, of whom 1, 2, and 4, respectively had non-alcoholic pancreatitis. The high incidence of pancreatitis suggested that branch fusion is the cause of pancreatitis. In addition, evaluation of ERP images revealed Santorini's duct originating from the ventral pancreatic duct in 5 patients with type 1 branch fusion, suggesting the presence of the ansa pancreatica proposed by Dawson. This finding may also be closely associated with the development of pancreatitis. (Dig Endosc 1994; 6 : 87–93)     

Effects of stress on growth of transplanted hepatic tumours and immune responses

Growth of transplanted hepatic tumours (T-9) was enhanced in immune rats under stress, compared with immune rats in an unstressed condition. Compared with unstressed immune rats, killer activity of mononuclear cells infiltrating the tumours against T-9 cells was significantly reduced in stressed immune rats. In contrast, killer activity of splenocytes obtained from stressed immune rats against T-9 cells was elevated compared with that from unstressed immune rats. In addition, natural killer cell activity of mononuclear cells infiltrating the tumours obtained from stressed immune rats was significantly reduced compared with that from unstressed immune rats. Cell populations infiltrating tumour tissues were identified by flow cytometric analysis. The percentage of CD8+ cells in mononuclear cells isolated from tumour tissues of stressed immune rats was reduced compared with that of unstressed immune rats. Furthermore, interleukin-2 responsiveness of splenocytes was suppressed in stressed immune rats, whereas T cell function as reflected by phytohaemagglutinin- or Concanavalin A-reactivity was unaffected by stress. Collectively, it is likely that stress suppressed the generation of cytotoxic cells from the spleen cells of immune rats.     

>CASE REPORT: Eosinophilic colitis with high antibody titre against Ascaris suum

Eosinophilic gastroenteritis (EGE) is an inflammatory disease characterized by eosinophilic infiltration of the gastrointestinal tract accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. Although the precise aetiology of EGE remains to be determined, contribution of allergic process to certain allergens, such as foods, drugs and parasites, has been repeatedly proposed as the pathogenesis of the disease. Here we report on a rare case of a woman who had extensive eosinophilic infiltration in the descending and rectal colon with a high titre of IgG antibody against Ascaris suum. The patient was successfully treated with prednisolone.     

Properties of the binding sites of [3H]9-methyl-7-bromoeudistomin D in bovine aortic smooth muscle microsomes

Abstract— [³H]9-Methyl-7-bromoeudistomin D ([³H]MBED), a powerful caffeine-like Ca²⁺ releaser, binds to the caffeine binding site of terminal cisternae of skeletal muscle sarcoplasmic reticulum and activates Ca²⁺-induced Ca²⁺ release. Properties of the binding site of [³H]MBED were investigated in aortic smooth muscle. The specific activity was higher in microsomes than in other fractions. [³H]MBED binding sites in smooth muscle microsomes were of a single class with a high affinity (K_D 50 Nm ), comparable with that in skeletal muscle sarcoplasmic reticulum. Caffeine competitively inhibited [³H]MBED binding, indicating MBED shares the same binding site with caffeine. Solubilization and fractionation of the microsomes gave two fractions of [³H]MBED binding activities. These results suggest that, in smooth muscle, there are multiple binding sites of [³H]MBED and caffeine, which might correspond to different pharmacological actions of caffeine on smooth muscle. Therefore, [³H]MBED, which binds to the different binding sites of caffeine, is useful as a probe for investigation of the actions of caffeine at the molecular level.     

Anti-HCV immunoglobulin M antibody in patients with hepatitis C

Anti-hepatitis C virus (HCV) immunoglobulin M antibody titres were measured by an enzyme-linked immunosorbent assay method in 16 patients with non-A, non-B acute hepatitis (NANB AH), 13 with non-A, non-B fulminant hepatitis (NANB FH) and nine with type C chronic hepatitis. Anti-HCV IgM was positive in one of the 16 patients with NANB AH, six of the 13 with NANB FH, and five of the nine with type C chronic hepatitis. Anti-HCV IgG was positive in eight of the 16 patients with NANB AH and eight of the 13 with NANB FH. Either anti-HCV IgM or anti-HCV IgG were positive in 10 of the 13 patients with NANB FH. All of the five anti-HCV IgM positive patients with type C chronic hepatitis were undergoing an exacerbation of the diseases, while all of the anti-HCV IgM negative patients were in a remission stage which had lasted for more than 6 months. The findings of this study suggest that anti-HCV IgM is useful for the early diagnosis of type C FH and may be a useful marker of diseases activity in type C chronic hepatitis.     

"Flare" Followed by Successful Tamoxifen Therapy in Two Cases of Advanced Breast Cancer

An antiestrogen, tamoxifen, is an effective drug in the treatmentof advanced breast cancer. The drug is generally very well toleratedand serious side effects such as the so-called "flare in thetumor" have rarely been observed. We have had two patients withadvanced breast cancer who showed the "flare" soon after theinitiation of tamoxifen therapy, and both patients finally achievedpartial response to tamoxifen. It is important not to misinterpretthe "flare" as progressive disease during tamoxifen therapy.