Estrogen Receptor in Malignant and Benign Breast Tumors and Normal Breast Tissues of Japanese Patients

Estrogen receptor (E-R) in breast tumors of patients who wereoperated at Keio University Hospital was examined routinely.During 10 months from May 1976 till March 1977, 65 breast cancertissues and 35 benign breast tumors were assayed and 47 surroundingtissues which seemed normal macro-scopically was removed fromthe mastectomied breast and assayed as control. E-R was evaluatedfrom the points of quantity, specificity and affinity. The simplemethod of assaying E-R with a single point for routine clinicaluse was described. The positive ratio of E-R in the breast cancerwas 55%. The breast cancer tissues obtained from postmenopausalpatients had higher level of E-R content than those from thepremenopausals. All of the E-R positive cancers; compared with"normal" tissues, had remarkably higher E-R level. The benignbreast tumors also had higher E-R content which was significantlydifferent from the "normal" surrounding breast tissues, suggestingthat some benign breast tumors may be hormone-dependent. Theincidence of E-R positive benign breast tumor and E-R positive"normal" breast tissue in Japanese patients was higher thanthat in patients in western countries. The dissociation constant(Kd) of the receptor in E-R positive breast cancers ranged from0.12 x 10^–10M to 4.76 x 10^–0 [1.07 ± 0.91)x 10^–0 (mean ± S.D.)]. The specific E-R had muchstronger affinity than other non-specific proteins. There wasno correlation between the histological type of tumors and theE-R level. There was also no correlation between the clinicalstage of the patients and E-R content of the tumors.     

Type II antithrombin deficiency caused by a large in‐frame insertion: structural,functional and pathological relevance

Summary. Background: The metastable native conformation of serpins is required for their protease inhibition mechanism, but also renders them vulnerable to missense mutations that promote protein misfolding with pathological consequences. Objective: To characterize the first antithrombin deficiency caused by a large in‐frame insertion. Patients/Methods: Functional, biochemical and molecular analysis of the proband and relatives was performed. Recombinant antithrombin was expressed in HEK‐EBNA cells. Plasma and recombinant antithrombins were purified and sequenced by Edman degradation. The stability was evaluated by calorimetry. Reactive centre loop (RCL) exposure was determined by thrombin cleavage. Mutant antithrombin was crystallized as a dimer with latent plasma antithrombin. Results: The patient, with a spontaneous pulmonary embolism, belongs to a family with significant thrombotic history. We identified a complex heterozygous in‐frame insertion of 24 bp in SERPINC1, affecting strand 3 of β‐sheet A, a region highly conserved in serpins. Surprisingly, the insertion resulted in a type II antithrombin deficiency with heparin binding defect. The mutant antithrombin, with a molecular weight of 59 kDa, had a proteolytic cleavage at W49 but maintained the N‐terminal disulphide bonds, and was conformationally sensitive. The variant was non‐inhibitory. Analysis of the crystal structure of the hyperstable recombinant protein showed that the inserted sequence annealed into β‐sheet A as the fourth strand, and maintained a native RCL. Conclusions: This is the first case of a large in frame‐insertion that allows correct folding, glycosylation, and secretion of a serpin, resulting in a conformationally sensitive non‐inhibitory variant, which acquires a hyperstable conformation with a native RCL.     

Idiopathic Premature Ventricular Contraction Conducting over a Ventricle Myocardial Extension from the Pulmonary Artery

Ventricle myocardial extensions (VMEs) from the right ventricular outflow tract to the pulmonary artery (PA) serve as arrhythmogenic foci for idiopathic ventricular arrhythmias (VAs). Although an autopsy study revealed the heterogeneity of the VME, only the electrocardiographic features of PA‐VAs arising from septal VMEs have been discussed. Here, we describe a case of idiopathic PA‐VAs conducting over a VME accompanied by unique ventricle activation patterns, which contributed to the appearance of an S wave in the inferior limb leads despite an arrythmogenic focus in the outflow tract.     

Hybrid Therapy of Radiofrequency Catheter Ablation and Percutaneous Transvenous Mitral Commissurotomy in Patients With Atrial Fibrillation and Mitral Stenosis

AF Ablation and PTMC. Background: The rhythm control of atrial fibrillation (AF) associated with mitral stenosis (MS) is often difficult using antiarrhythmic drugs (AADs), even after a percutaneous transvenous mitral commissurotomy (PTMC). Few studies have examined the efficacy and safety of simultaneously performing radiofrequency catheter ablation (RFCA) and a PTMC in patients with MS and AF. Methods: Twenty consecutive patients with drug‐resistant AF and rheumatic MS underwent RFCA combined with a PTMC (n = 10; persistent AF‐8, long‐lasting [>1 year] persistent AF‐2; RFCA group) or transthoracic direct cardioversion (DC) following a PTMC (n = 10; persistent AF‐7, long‐lasting persistent AF‐3; DC group). In all patients, the mitral valve morphology was amenable to a PTMC, and more than 2 AADs had been ineffective in maintaining sinus rhythm (SR). In the RFCA group, a segmental pulmonary vein isolation (PVI) was performed in the initial 5 patients, and an extensive PVI was performed in the remaining 5. Results: During a mean follow‐up period of 4.0 ± 2.7 years, 8 patients (80%) in the RFCA group were maintained in SR, as compared to 1 (10%) in the DC group (hazard ratio, 0.16; 95% confidence interval, 0.03 to 0.75; P = 0.008 by the log‐rank test). The prevalence of the concomitant use of class I and/or class III AADs was comparable between the 2 groups (P = 0.70). No complications occurred during the procedure or follow‐up period in either group. Conclusions: The hybrid therapy using RFCA and a PTMC was safe and feasible, and significantly improved the AF free survival rate compared to DC following a PTMC. (J Cardiovasc Electrophysiol, Vol. 21, pp. 284–289, March 2010)     

Chronic expanding hematoma in the psoas muscle

We report an unusual case of chronic expanding hematoma in the psoas muscle. A 53-year-old man was admitted for evaluation of a mass shadow in the left lower lung field on chest X-rays. He had also been suffering from dull left back pain. A computed tomography scan showed a cystic lesion with a rim enhancement in the left retroperitoneal space. Mixed signal intensity in a mosaic pattern was seen on a T2-weighted magnetic resonance image. We could not rule out a suspicion of a neoplastic intratumoral hemorrhage. Due to increased pain and the definite diagnosis, surgery was performed. Histopathological examination confirmed the diagnosis of chronic expanding hematoma. The expansion process is thought to be due to the irritant effects of blood and its breakdown products, which cause repeated exudation and bleeding from capillaries in the granulation tissues.     

Characterization of mucin in the hepatic bile of patients with intrahepatic pigment stones

To investigate the relationship between biliary mucin and ductular stone formation, mucin was isolated from hepatic bile using gel filtration on Sepharose CL-4B. The bile was obtained from 14 patients with stones in various sites of the biliary tract. The hexose content in the excluded fraction was significantly higher in patients with intrahepatic ductular stones (68.7 +/- 20.5 micrograms/mL; mean +/- s.d.) than in those with gall-bladder stones or extrahepatic ductular stones (23.8 +/- 8.1 micrograms/mL, 33.3 +/- 9.5 micrograms/mL; P less than 0.05), suggesting a higher concentration of mucin in the bile of patients with intrahepatic ductular stones. Ion-exchange chromatography on DEAE-Sephacel showed that most mucin from each material was negatively charged and electrophoretic studies indicated that it was composed mainly of high molecular weight (greater than 10(6)), sulfated glycoprotein. These results suggested that the mucin content of hepatic bile might have an important relation to the development of intrahepatic ductular stones.     

Blood Group Antibody Levels in Hiroshima

Blood group antibody levels were measured in 526 irradiated survivors ofthe 1945 atomic bombing of Hiroshima and in 516 nonirradiated subjects. Thestudy was undertaken in order to determine the age changes in antibody levelsin irradiated and nonirradiated subjects, as well as to investigate the patternof blood agglutinin levels in the Japanese population for comparison with thatof Caucasians. The following observations were made:

1. In 475 people of group A, 228 of group B, and 339 of group O, the meanserum levels of anti-A and anti-B antibodies were virtually identical irrespective of the blood group of the subjects.

2. In individual group O subjects, the titers of anti-A and anti-B antibodieswere very highly correlated (correlation coefficient of +.92).

3. Females exhibited higher antibody levels, although the magnitude of thedifference was small.

4. Peak antibody titers were reached at age 20-30, with progressive linearregression in levels with advancing age. Peak titers in early adulthood were5-10 times higher than those of the very elderly.

5. No correlation between blood group antibody levels and atomic irradiationwas detected, whether irradiation was represented by (a) presence or absenceof acute radiation symptoms in 1945, (b) distance from the hypocenter, or(c) numerical dosage estimate.

6. As one of a battery of tests of physiologic aging designed for detection ofirradiation induced nonspecific aging acceleration, blood group antibodylevels seem of modest value. After age 30, the linear correlation with chronologic age is -.72.

7. Differences in blood group antibody levels in Japanese and Caucasiansindicate that (a) Caucasians have higher anti-A antibody levels as comparedto anti-B levels than do Japanese, and (b) the peak antibody level occurs atan earlier age in Caucasians than in Japanese. It is not clear whether thesedifferences are related to race and heredity or to external antigenic stimulationwith A and B antigenic materials, but studies of blood group antibody levelsin different racial groups should help elucidate the nature of these differences.

Accepted on January 20, 1961     

Source of plasma adrenomedullin in a patient with pheochromocytoma receiving hemodialysis

Abstract  A 45-year-old man on long-term hemodialysis (HD) was incidentally discovered to have a pheochromocytoma and underwent successful resection. This patient was normotensive, and had no symptoms suggesting pheochromocytoma. The plasma concentrations of total adrenomedullin (AM-T) and mature AM (AM-m) were higher than those in normal controls. To elucidate the source of AM, we measured plasma AM levels by immunoradiometric assay before and 3 weeks after surgery in addition to plasma adrenaline, noradrenaline and dopamine. AM expression was also assessed by immunoblot and immunohistochemical analyses on normal adrenal and tumor tissues. After surgery, elevated plasma adrenaline levels returned to the normal range; however, the levels of AM-T and AM-m remained almost the same as the preoperative values. Furthermore, although AM was expressed in both normal adrenal and tumor tissues, the AM expression level was less in tumor. In this case, it was suggested that elevation in plasma AM level might be a factor associated with normotensive blood pressure; however, adrenal pheochromocytoma was not a major source of circulating AM. To our knowledge, this is the first case of pheochromocytoma in patient with HD associated with AM in the literature.     

Recto-peritoneal fistula following transperineal prostate biopsy

A recto-peritoneal fistula is an extremely rare complication after prostate biopsy. We report herein on a peritonitis arising from a recto-peritoneal fistula 5 days after undergoing prostate biopsy. To our knowledge, this is the first case of recto-peritoneal fistula following transperineal needle biopsy of the prostate in the published literature.     

Traumatic renal artery thrombosis with renovascular hypertension

A 15-year-old boy, who tumbled from a fourth-floor window, was transported to our hospital. Enhanced computed tomography (CT) 1.5 h after the injury showed a non-contrasted right kidney, and a repeat CT 6 h after the injury showed a growing retroperitoneal hematoma. The angiography showed complete obstruction of the right renal artery and bleeding from the subcapsular artery, which was successfully embolized. Renovascular hypertension developed on the second day after the injury; therefore, simple nephrectomy was performed.