Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels.

PURPOSE: There are no available tumor markers detecting primary melanoma at an early stage. The identification of such serum markers would be of significant benefit for an early diagnosis of melanoma. We recently identified glypican-3 (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby, we focused out attention on secreted protein acidic and rich in cysteine (SPARC) overexpressed in melanoma as another candidate for tumor marker. EXPERIMENTAL DESIGN: Secreted SPARC protein was quantified using ELISA in the sera from 109 melanoma patients, five patients with large congenital melanocytic nevus, 61 age-matched healthy donors, and 13 disease-free patients after undergoing a surgical removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples and compared these markers for their diagnostic value. RESULTS: The serum SPARC concentrations in melanoma patients were greater than those in healthy donors (P = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the healthy donors, the serum SPARC was found to have increased in the sera of 36 of the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased SPARC levels were in stages 0 to II. The serum SPARC level decreased under the cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an early stage (0-II). CONCLUSIONS: SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage.     

Successful bronchial artery embolization using hydrogel coils for hemoptysis during extracorporeal membrane oxygenation

A 58-year-old woman with bronchiectasis presented with massive hemoptysis and severe respiratory failure, which required long-term extracorporeal membrane oxygenation with continuous heparin infusion. Bronchial artery embolization using hydrogel coils, which provide a greater volume occlusion than bare platinum coils, was performed; hemoptysis stopped and she fully recovered. No recanalization was observed on follow-up computed tomography angiography 2 months postbronchial artery embolization, and there had been no recurrence of bleeding at the time of this report (at least 6 months). Although continuous anticoagulation during extracorporeal membrane oxygenation might hinder complete vessel occlusion by metallic coils or induce early recanalization (because the homeostatic mechanism of coils depends on the patient''s coagulability), our experience showed that bronchial artery embolization using hydrogel coils was effective and safe. Additionally, this case presents a successful example of anticoagulation management for patients with hemoptysis on extracorporeal membrane oxygenation who undergo bronchial artery embolization using coils.     

Studies on rennin as a virus-model. II. resemblance of rennin to some viruses in its physical and chemical properties

Summary Rennin is regarded as being similar to viruses such as vaccinia and phage in its physical and chemical properties. Rennet activity is carried by a lipoprotein existing in particles or micells of very great dimensions.Coagulation of milk by rennin can be considered to be a chain reaction to some extent.     

Resorption and excretion of glucose by the particle of minute-body-forming proteid,including virus proteid

Summary The resorption and excretion of glucose by living cells can be explained to be due to a property of the minute-body-forming proteid existing in the cells.Also in this property, there is no difference between virus proteid (vaccinia) and the normal minute-body-forming proteid having no virus action.     

Absorption of inorganic salts and sugars by vaccinia and by coagulated casein particles

Summary The salt-impenetrable space of vaccinia particles isolated from vaccine pulp by isoelectric precipitation method was estimated by measuring the salt quantity added to the suspension of the vaccinia particles of a known concentration, which were centrifuged off after the addition of the salt at a weakly acid p_H (about 5,4). The salts used were NaCl, KCl and CaCl₂. It was found thus that salt-impenetrable space of the particles varied with the concentrations of the salts, in the solution of which the particles were suspended. There was no definite relation between the concentration of the salt and the volume of the space.The shape of the curve representing the relation between the volume of the space and the concentration of a salt was different with each preparation of the vaccinia particles, and the curve was also different with each kind of the salts; even with the same preparation different curves were obtained if the experiments were carried out at different temperature.Similar experiments were made also with glucose and fructose. These two monosaccharides behaved themselves in a very complicated manner towards the particles, in assuming a different attitude from each other, although the shape of the curve tended in most cases to be alike with each other. As already pointed out lactose did not assume so complicated an attitude as did glucose.These phenomena were not peculiar to the vaccinia particles, but also found with coagulated casein particles as well as with protoplasmprotein particles having no virus action.     

The inactivation of phage protein by neutralization of its acidified solution

Summary Moriyama has previously isolated a vaccinia virus protein which is severely inactivated if its acidified solution is neutralized in the presence of inorganic salts, while the inactivation scarecely occurs if no salt is present in the neutralization process. Afterwards we have also observed a similar phenomenon with a phage protein though not so manifest as with the vaccinia protein.We have lately found that a phage protein (coli-phage) can possess sometimes a property to be damaged severely if its acidified solution is neutralized in a water medium containing no salt: in this case inorganic salts can, on the contrary, prevent the inactivation. This fact must be taken into considerations in our isolating method of virus proteins. Namely in some cases a proper salt solution such asRinger's and a dilute CaCl₂ solution should be used instead of water.     

Die Verkürzungsstufen und Gewichtsänderungen von Muskeln und Drüsen bei der Wärmestarre in verschiedenen Lösungen

Ohne ZusammenfassungZum Schlusse möchte ich Herrn Prof.E. Mangold für die Anregung und Anleitung bei diesen Untersuchungen meinen herzlichsten Dank aussprechen.     

Surveillance study for creating the national clinical database relating to ECG-gated myocardial perfusion SPECT of asymptomatic ischemic heart disease in patients with type-2 diabetes mellitus: J-ACCESS 2 study design

Objective Diabetes mellitus is an independent risk factor for acute myocardial infarction. Thus, a surveillance study was conducted as part of studies to create a national database related to electrocardiogram (ECG)-gated myocardial perfusion single-photon emission computed tomography (SPECT) of ischemic heart disease. Methods Single-photon emission computed tomography was conducted in patients with type 2 diabetes mellitus and their prognoses will be followed for 3 years, stratified by patients’ clinical background and SPECT findings. Results A total of 513 patients from 50 institutions were enrolled in this study, 297 of whom were men (age 66.2 ± 0.4 years, mean ± SEM) and 261 women (age 67.8 ± 0.5 years). They have a history of retinopathy (25.3%), neuropathy (19.9%), cerebrovascular disorder, chronic obstructive pulmonary disease, and photocoagulation. Major risk factors for present disease were hypertension (82.3%) and hyperlipidemia (79.7%). In 244 patients (129 men and 115 women), body mass index (BMI) was 25 or more. Fifty-two of them (10.1%) underwent coronary angiography; of these, 26 (50.0%) had no coronary artery lesions with 75% or more stenosis, and only 1 (1.9%) had a left main trunk with 50% or more stenosis. An overwhelming majority of patients (94.3%) underwent SPECT imaging by a 1-day stress-followed-by-rest procedure. Stress procedure was exercise in most (70.8%) patients, followed by dipyridamole infusion in 14.6%, adenosine infusion in 6.6%, and adenosine triphosphate infusion in 5.7%. Endpoint of stress examination was most often fatigue in lower limbs (40.7%), followed by completion of pharmacological stress protocol (28.7%), and achievement of target heart rate (26.3%). The largest number of patients (198, 38.6%) received ^99mTc-tetrofosmin at an initial dosage of 200–300 MBq (mean 331 ± 3 MBq) followed by a second dosage of 700–800 MBq (mean 748 ± 8 MBq). Among them, 491 (95.7%) received some kind of therapeutic drug: hypoglycemic drugs were used by the largest number (83.2%), followed by hypotensive (66.7%), hypolipidemic (40.7%), and antiplatelet drugs (27.7%), vasodilators (5.5%), and antioxidants and others (2.3%). Conclusions This study was designed to clarify the correlation between coronary artery disease and diabetes mellitus as its risk factor based on the clinical and imaging findings. Patient enrollment was closed on September 30, 2005, and follow-up is now under way.