Functional Communication Between Cardiac ATPSensitive K+ Channel and Na/K ATPase

K_ATP Channel and Na/K ATPase. Introduction: Functional interaction between K_ATP channel and Na/K ATPase was studied in single guinea pig ventricular myocytes because both membrane molecules are known to he involved in ischemic episodes. Methods and Results: K_ATP channel currents were recorded at 36°C by using whole cell, cell attached, inside-out, and open cell-attached modes of patch clamp techniques on enzymatically isolated ventricular myocytes. In the whole cell mode, ouabain (1 μM) reversibly inhibited the K_ATP currents induced by metabolic stress (ATP-free pipette solution and 1 mM NaCN), but not those activated by cromakalim (100 μM), a K_ATP channel opener. In the cell-attached mode, ouabain concentration dependently inhibited K_ATP, channel opening induced by metabolic suppression (5.5 μM 2-deoxyglucose and 1 mM CN). Half-inhibition concentration for ouabain was 21.0 ± 5.5 nM and the Hill coefficient was 0.8 ± 0.1 (n = 26). However, ouabain did not have an effect on the channel activity induced by cromakalim (100 μM). In the inside-out mode, ouabain applied to the internal side of membrane did not affect the channel. In the open cell-attached mode made by preincubation with streptolysin-0 (0.08 U/mL), the K_ATP channels were not activated by the metabolic inhibitors but were by reducing extracellular ATP concentrations, because subsarcolenimal ATP concentration could he controlled through tiny membrane holes. The channels thus activated were not suppressed by ouabain. Conclusion: The inhibition of Na/K ATPase by ouahain appeared to block the K_ATP channels by accumulating subsarcolemmal ATP caused by a decrease of the transition from ATP to ADP. In the presence of ischemic episodes, the administration of digitalis compounds may affect the opening of K_ATP channels, which is primarily protective against the development of irreversible myocardial damage.     

A Case of Crohn's Disease which Initially Presented with Diffuse Inflammation in the Rectum and Sigmoid Colon

Abstract: This case report describes a female patient with Crohn 's disease who had diffuse proctosigmoiditis without a longitudinal ulcer or cobblestone appearance at the initial attack. She was treated with sulfasalazine on the presumptive diagnosis of ulcerative colitis. Two and a half months later, painful ulcers in the oral cavity and a deep longitudinal ulcer in the sigmoid colon were found, and a non-caseous granuloma was revealed in the biopsy specimens taken from the sigmoid colon. A definitive diagnosis of Crohn's disease was established from these findings and treatment with a corticosteroid was effective.     

Clinical characteristics of normotensive renal transplant recipients with microalbuminuria and effects of angiotensin II type I receptor antagonist on urinary albumin excretion

AIM: Microalbuminuria is typically observed in renal transplant recipients with systemic hypertension. The effects of angiotensin II type 1 receptor antagonist (losartan) on the hypertensive recipients have been evaluated. However, the clinical background of normotensive recipients with microalbuminuria and the effect of losartan administration in those subjects have not been clarified. One of the two purposes for the present study was to investigate the clinical characteristics of normotensive recipients with microalbuminuria. The other was to evaluate the effect of losartan on urinary excretion of albumin in these patients. METHODS: The clinical data and the change of the single kidney glomerular filtration rate (GFR) for the graft by radionuclide study were assessed in 13 normotensive recipients with microalbuminuria. These were compared with the data of 13 normotensive patients without microalbuminuria. The 13 recipients with microalbuminuria were treated with losartan for one year and urine excretion of albumin, N-acetyl-beta-D-glucosaminidase (NAG) and serum creatinine (S-Cr) levels were measured. RESULTS: The GFR of the grafts from donors to recipients significantly increased (30.9 to 55.2 mL/min) in microalbuminuric recipients, but did not significantly increase in the non-microalbuminuric recipients. Decreases of the urinary excretion rate of albumin (351 +/- 261 at baseline to 158 +/- 14 mg/gCr at 12 months), NAG (13 +/- 5 to 10 +/- 3 IU/gCr) and S-Cr (1.7 +/- 0.6 to 1.5 +/- 0.4 mg/DL) were observed in the microalbuminuric recipients with losartan administration. CONCLUSIONS: The present study suggests that an increased single kidney GFR of the graft from the donor in situ to the recipient might be a cause of microalbuminuria in normotensive recipients. The one-year effects of losartan were observed in terms of the decrease in urinary excretion of albumin, NAG and S-Cr levels.     

Influence of pretransplant dialysis modality on the change of lymphocyte subset populations and acute rejection rates after renal transplantation

BACKGROUND: The influence of dialysis modality on the acute rejection (AR) rate after renal transplantation is controversial. We investigated whether the pretransplant dialysis modality correlated with the lymphocyte subset populations and the incidence of AR after renal transplantation. METHODS: Thirty-eight first living renal transplant recipients, consisting of 22 patients on pretransplant hemodialysis (HD) and 16 patients on pretransplant peritoneal dialysis (PD), were studied. Peripheral blood samples were taken on days -1 through 28 after transplantation, and the lymphocyte fractions were exposed to the monoclonal antibodies anti-CD3, CD19, CD4, CD8 and CD28 for a flow cytometer analysis. Biopsy specimens were obtained at the time of presumed AR episodes and on day 28 after transplantation. RESULTS: The PD patients had a higher frequency of AR (37.5% in PD vs 9.1% in HD patients, P = 0.034). In contrast, two HD patients showed graft loss at 18 and 30 months after transplantation. The increases of CD3, CD19, CD4 and CD4+ CD28+ cells in the PD patients occurred earlier than in the HD patients and the numbers of these cells in the PD group were higher than those in the HD between days 3-28 after transplantation, most significantly on day 7. CONCLUSIONS: These findings suggest that the PD patients with similar clinical characteristics could potentially have a higher immunocompetence and immune responsiveness associated with a higher rate of AR in the early stage of renal transplantation when compared with the HD patients.     

Immunoglobulin G subclass distribution of human anticolon antibodies in ulcerative colitis

Abstract Immunoglobulin G (IgG) subclasses of anticolon antibodies were studied in patients with ulcerative colitis (UC) using enzyme-linked immunosorbent assay (ELISA). The concentrations of total serum IgG subclasses were also measured by ELISA. The values for total serum IgG subclasses in patients with UC were not significantly different from those in normal controls, while the ratio of IgG₁ to IgG₂ in the patients was significantly higher than that in normal controls. All four IgG subclasses of autoantibodies were demonstrated in the sera of the patients. IgG₄ anticolon antibodies were detected most frequently (15 out of 18 patients, 83%). IgG₂ was the next most prevalent (9 of 18 patients, 50%). The activity of anticolon antibodies in each subclass did not correlate with the concentration of the corresponding serum IgG subclass. Seven cell lines producing anticolon antibodies were obtained from the colonic mucosa of the patients by Epstein-Barr virus (EBV) transformation. IgG subclasses of anticolon antibodies secreted by these cell lines were also varied. IgG₄ subclass was secreted by three EBV transformed cell lines, all of which produced IgG₄ anticolon antibodies. These results suggest that all four different IgG subclasses could respond to the colon antigens and that various antigens in colonic mucosa or lumen may contribute to the induction of those autoantibodies. In addition, the prominence of IgG₄ anticolon antibodies may support the pathogenic role of this subclass in UC as in other autoimmune diseases.     

Effect of testosterone on the mucosal defence against intestinal helminths in Indian soft-furred rats, Millardia meltada with reference to goblet and mast cell responses

Effects of testosterone on the mucosal defence mechanisms against intestinal helminths were examined in Millardia meltada. When female M. meltada were treated with testosterone at the pharmacological dose, Nippostrongy-lus brasiliensis infection persisted for over seven weeks with prominent biphasic pattern of faecal egg production, whereas almost complete expulsion was observed by two weeks in untreated controls. In spite of a biphasic pattern of faecal egg production, the worm burden of testosterone-treated animals remained constant up to three weeks and then slowly decreased by seven weeks. To see whether or not this delayed expulsion in testosterone treated animals was due to altered cellular responses of the intestinal mucosa, goblet and mast cell responses were examined histologically. At two weeks post-infection, goblet cell responses at the infected site were significantly lower in testosterone-treated animals than in controls. In contrast mast cell hyperplasia was comparable between testosterone-treated and control animals. When Strongyloides venezuelensis, in which expulsion is dependent on mucosal mast cells, were infected concurrently with N. brasiliensis, testosterone-treated animals could expel S. venezuelensis worms by Day 18, but failed to expel N. brasiliensis. Histologically, mast cell hyperplasia was associated with expulsion ofS. venezuelensis, while goblet cell responses were suppressed. From these results, testosterone seems to suppress proliferation/function of goblet cells but does not affect mast cells ofM. meltada.     

Immediate and Delayed Cardiac Herniations after Intrapericardial Pneumonectomy--Report of Two Cases

Two cases of cardiac herniation following intrapericardial lungresections were reported. One was a case of a 29-year-old male with adenocarcinoma ofthe right lower lobe and the other was a 43-year-old male withsquamous cell carcinoma of the right upper lobe of the lung. In the former, cardiac herniation occurred in the recovery room.In the latter, it occurred during the second operation repairingbronchial fistula which appeared 20 days after the previousintrapericardial surgery. The time delay in the second casewas due to the unsuitable quality of prosthesis for the pericardialdefect.     

An Approach to the Detection of Autonomic Neuropathy hy Use of Signal-Averaged Electrocardiography

The beat-to-beat variation of PR interval, which is thought to be a reflection of autonomic nervous system, is difficult to measure with accuracy because the variation is too subtle. However, R wave amplitude in the P wave triggered SAECG is easily attenuated in comparison to that in the R wave triggered SAECG, which might he due to PR interval fluctuation. To determine whether autonomic neuropathy could be detected by use of SAECG, two types of SAECGs triggered by P and R waves were recorded in 23 diabetics with autonomic neuropathy and 41 age matched controls. The peak voltage of filtered QRS complex was measured in the R wave and P wave triggered SAECGs. Percent attenuation of the filtered QRS voltage was calculated by dividing the difference between the voltages in the R wave and P wave triggered SAECGs by the voltage in R wave triggered SAECG. The percent attenuation of filtered QRS voltage was significantly smaller in diabetics with autonomic neuropathy than controls (4.6%± 4.9% vs 16.3%± 15.0%; P < 0.001). These results suggest that the degree of attenuation of filtered QRS voltage in the P wave triggered SAECG would be useful for the detection of autonomic neuropathy.     

A Study on Time- and Radiation-dependent Changes in the Frequency of Lymphocytes with Chromosome Aberrations in the Circulation, Following Multiple Exposures of the Pelvis to ggr-Irradiation

Unstable chromosome aberrations ofperipheral lymphocytes were observedduring the course of radiotherapy in patients with cervical cancer. They did notincrease monotonously with repeated exposures, but a plateau was observedaround the second week of treatment.Similar tendencies were observed in both72-hour and 50-hour culture experiments, although the number of abberrations was lower in the former. Thedistribution of numbers of dicentrics percell fitted well the Poisson patternthroughout the period of observation.Peripheral lymphocyte counts reached alow plateau before the fifth exposure,and dropped again in the third week.It was speculated that the "member exchange" and/or mobilization of lymphocytes caused the nonlinear increase inchromosome aberrations.

Submitted on December 7, 1969 Accepted on January 22, 1970