Estimation of the malignant potential of gastrointestinal stromal tumors: the value of contrast-enhanced coded phase-inversion harmonics US

Background Recently, contrast agents for ultrasonography (US) such as Levovist have been introduced for routine clinical use. The contrast-enhanced US with Levovist permits evaluation of the intratumoral vascularity of hepatic and pancreatic tumors and is useful for their differential diagnosis. The purpose of the present study was to assess tumor vessels and the parenchymal flow of gastrointestinal stromal tumors (GISTs) by contrast-enhanced coded phase-inversion harmonic US and to evaluate whether vascularity is related to the malignant grade of the GISTs.Methods Thirteen patients with GISTs were included in the present study. Tumors were observed in a real-time fashion of contrast-enhanced coded phase-inversion harmonic US after the injection of Levovist (400mg/ml). The vascular patterns were compared with tumor size, histological diagnosis, KIT mutations, and clinical findings such as metastasis.Results The contrast-enhanced US images of the GISTs were classified into two types according to the blood flow area of the tumors as seen by real-time continuous imaging of the tumor vessels. The image pattern Poor represented vessels flowing only in the peripheral part of the tumor, and Rich represented abundant vessels flowing from the periphery to the central part of the tumor. According to the contrast-enhanced US images, five GISTs were classified as Poor and the others as Rich. Based on the final diagnosis, all tumors with Poor images were determined to be benign GISTs, and the rest tumors except one with Rich images were determined to be malignant GISTs.Conclusions Contrast-enhanced US image is more closely correlated with the final diagnosis than the histological findings.     

Compound heterozygosity for a β∘-thalassemia (frameshift codons 38/39; -C) and a nondeletional swiss type of HPFH (A→C at NT -110, Gγ) in a Czechoslovakian family

Summary We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered -thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an AC mutation at nucleotide –100 5 to the Cap site of G), or with a compound heterozygosity for these two conditions. The Hb F level in the -thalassemia heterozygotes averaged 0.3% with low G values ( 28%) and relatively high AT values ( 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with 95% G, while that of the compound heterozygote was 3.1% with 95% G. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%–0.2% Hb F level [3]. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.This study was supported in part by USPHS Research Grant HLB-41544     

Distribution pattern of α and β myosin in normal and diseased human ventricular myocardium

Summary All fibers in three normal, four dilated, and two ischemic human ventricles were classified according to their myosin content using three sets of monoclonal antibodies each specific for one myosin heavy chain isoform (, and ). Numerous fibers contained only myosin heavy chain (denoted as fibers), others contained either and , or and myosin heavy chain (denoted as and fibers, respectively). The percentages of fibers were systematically determined along the walls of seven homologous regions of the ventricular myocardium.In all ventricles, there was an -fiber transmural gradient, with less fiber in the subendocardium than in the subepicardium. More fibers were found in the right than in the left ventricular wall but there was no difference between the mid-portion and the apex of the free wall of each ventricle. The diseased ventricles contained a lower fiber percentage than the normal hearts. fibers were very rare in the normal ventricles (less than 5%) and almost inexistent in pathological hearts. The correlation between the mean fiber percentages of the diseased hearts and their cardiac indices (r=0.88, P<0.05) suggests that the small amount of myosin distributed in a large number of ventricular fibers could play a role in the contractile performance of the heart. In conclusion, this study provides evidence for 1) an fiber transmural gradient, and 2) a lower myosin ratio in discased than in normal human ventricle.This work was supported in part by L'Institut National de la Santé et de la Recherche Médicale 101 rue de Tolbiac, 75013 Paris     

Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells

Aims/hypothesis Alpha1-proteinase inhibitor (1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of 1-PI is the liver, but other tissues, including pancreatic islets, also synthesise this molecule. The aims of this study were to assess the islet cell types that produce 1-PI, to determine whether 1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated.Methods Expression of 1-PI in human islet cells was assessed by immunofluorescence, electron microscopy and western blotting. Release of 1-PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of cytokines on 1-PI synthesis and secretion were tested.Results Immunofluorescence showed that alpha and delta cells do express 1-PI, whereas beta cells do not. By electron microscopy, we demonstrated a colocalisation of 1-PI with glucagon and somatostatin within secretory granules. Immunolabelling also revealed localisation of 1-PI within the Golgi apparatus, related vesicles and lysosomal structures. The expression of 1-PI in islet cells was also demonstrated by western blotting and ELISA of protein extracts. ELISA and reverse haemolytic plaque assay showed that 1-PI is secreted into the culture medium. Treatment of islet cells with IL-1 and oncostatin M for 4 days increased the production and release of 1-PI.Conclusions/interpretation Our results demonstrate that 1-PI is expressed by the alpha and delta cells of human islets, and that proinflammatory cytokines enhance the production and release of this inhibitor.     

Changes in expression levels of genes involved in fatty acid metabolism: upregulation of all three members of the PPAR family (α, γ, δ) and the newly described adiponectin receptor 2, but not adiponectin receptor 1 during neonatal cardiac development of the rat

During neonatal cardiac development, the heart changes its substrate preference from glucose to fatty acids. The aim of this study was to investigate the changes in mRNA expression levels of genes involved in the control of cardiac fatty acid metabolism in the transition from neonatal to adult life. Methods mRNA expression levels for peroxisome proliferator activated receptor (PPAR) , and , PPAR co–factor 1 and (PGC–1 and ), 9–cis retinoc–acid–activated receptor , and (RXR , , ), 5–AMP activated protein kinase (AMPK) 1 and 2, adiponectin receptor 1 and 2 (AR 1 and AR 2) were measured in heart tissue of neonatal 0–day, 7–day and 21– day old rats. Results mRNA expression of all three members of the PPAR family were upregulated significantly from day 0 to day 21 ( +117%, +133%, +203%). In addition, m–RNA expression of all RXR isoforms increased from day 0 to day 7 ( +125%, +69%; +41%). AR 2 exhibited a small but significant increase in mRNA expression (+ 46%). Conclusions We were able to demonstrate for the first time that in addition to PPAR, also PPAR and , as well as all RXR isoforms and AR 2 are upregulated in the heart during neonatal development.Drs. Steinmetz and Quentin contributed equally to this publication     

Distribution of β-Adrenoceptor Subtypes in Gastrointestinal Tract of Nondiabetic and Diabetic BB Rats A Longitudinal Study

The effects of aging and diabetes on thedistribution of -adrenoceptor subtypes in the gutwere investigated in the BB rat.[¹²⁵I]Cyanopindolol binding to 10-msections was evaluated using film autoradiography. Cyanopindolol binding to -,₁-, and₂-adrenoceptors was displaced by 1M propranolol, 50 nM ICI-89-406, and 100 nMICI-118-551, respectively. -Adrenoceptor bindingwas highest in the circular muscle of proximal colon and lowest in thepylorus of 4- to 5-month-old rats. Aging (8- to10-month-old vs. 4- to 5-month-old rats) was associatedwith increased -adrenoceptor binding in thepylorus and reduced binding in the proximal colon.Diabetes had a time-dependent effect on the level of-adrenoceptor binding. It was increased in theantral and pyloric stomach but longer periods ofdiabetes caused a reduction in -adrenoceptorbinding in the pylorus. Those in the intestine werereduced time-dependently and involved₁- or ₂-adrenoceptorsor both.     

Static exercise in anesthetized dogs,a cause of reflex alpha-adrenergic coronary vasoconstriction

Summary The coronary blood flow and vascular resistance responses to static hindlimb exercise were studied in 11 anesthetized dogs after - and combined - and -adrenergic blockade to determine if this stress causes coronary vasoconstriction. After -blockade static exercise increased the blood pressure and double product, but decreased the right and left ventricular (LV) coronary blood flow and increased the coronary vascular resistance. These vascular changes primarily occurred in the epicardial and mid-myocardial but not the endocardial layers of the LV. Following combined - and -adrenergic blockade, the systemic hemodynamic and coronary flow and resistance changes were abolished. These data suggest that -adrenergic mediated coronary vasoconstriction occurs during static hindlimb exercise in dogs.Dr. Longhurst is partially supported by an NIH Young Investigator Award, #HL-22667. Dr. Aung-Din is presently a resident in Neurosurgery at the University of Florida, Gainesville, Florida.     

Analytical Performance of the New Coagulation Monitoring System INRatio™ for the Determination of INR Compared with the Coagulation Monitor Coaguchek® S and an Established Laboratory Method

An evaluation of the INRatio Prothrombin Time Monitoring system for determination of INR was done in two centers with a total of 5 healthy subjects and 77 subjects on oral anticoagulation. The INRatio and the Coaguchek® S were compared with an established laboratory method. The correlation coefficient of the comparison with the laboratory was r = 0.954 for INRatio and r = 0.937 for Coaguchek® S. The mean relative deviation from the lab method calculated according to Hill was 6.87% for INRatio, which is rated very goo, and 9.72% for Coaguchek® S (goo). The imprecision in the normal range (INR = 1.1) showed a coefficient of variation (CV) of 7.8% and a standard deviation (SD) of 0.09. In the therapeutic range (INR 3.9) the CV was 5.4%, the SD 0.21 and above therapeutic range (INR 5.3), the CV was 8.4% (SD 0.44), rated satisfactory. The concordances of the compared methods with the routine were 81% for INRatio and 79% for Coaguchek® S, which is considered state-of-the-art. Most of the patients perceptions of the INRatio were very positive.In the hands of professionals the INRatio demonstrated very good accuracy and precision and an excellent technical reliability. Further studies using INRatio for self testing by patients are warranted.     

Takayasu’s arteritis and chronic autoimmune thyroiditis in a patient with type 1 diabetes mellitus

Takayasus arteritis is a rare, chronic inflammatory disease of unknown origin, affecting the walls of the aorta and its main branches, as well as coronary and pulmonary arteries. The inflammation of the arteries may lead to stenosis, occlusions, dilatations, and aneurysms of involved vessels. It is relatively common in Asia and the Far East but is rare in the Western Hemisphere. We present the case of a 36-year-old white woman with a history of type 1 diabetes mellitus and chronic autoimmune thyroiditis who complained of easy fatigability in the upper limbs, with absent arterial pulses in the upper limbs and audible bruits over both subclavian and left common carotid arteries. Intra-arterial digital subtraction angiography revealed complete or subtotal obliteration of the aortic archs branches, with the brain supplied with blood only by the left vertebral artery originating directly from the aortic arch. We diagnosed Takayasus arteritis with abnormal origin of the left vertebral artery. To the best of our knowledge, our case of Takayasus arteritis and chronic autoimmune thyroiditis in a type 1 diabetic patient with abnormal origin of the left vertebral artery is the first one ever described.     

Regulation of large coronary vessels by adrenergic mechanisms in conscious dogs

Summary The effects of and adrenergic stimulation were examined in conscious dogs on measurements of left circumflex coronary blood flow and coronary arterial diameter and on calculations of mean coronary resistance (MCR) and left circumflex coronary internal cross-sectional area (CSA). Methoxamine (50 g/kg/min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex coronary diameter (9±2%) and CSA (27±5%) at a time when mean arterial pressure rose by 65±5%, left ventricular (LV) dP/dt had decreased only slightly, and heart rate and mean coronary blood flow were at control levels. Isoproterenol, (0.1 g/kg/min), increased heart rate by 66±8%, LV dP/dt by 58±5%, and CSA by 17±3%, while it decreased mean arterial pressure by 12±1% and MCR by 44±5%. After ₁ adrenergic receptor blockade and with heart rate held constant, isoproterenol did not increase LV dP/dt but decreased mean arterial pressure similarly (13±2%) and induced attenuated increases in CSA (6±1%), and decreases in MCR (17±3%). After combined ₁ and ₂ adrenergic receptor blockades isoproterenol induced no significant effects.Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial active changes. Alpha adrenergic stimulation is sufficiently powerful to reduce CSA, despite the opposing elevation of distending pressure. Moreover, large vessels appear to be regulated by ₁ adrenergic mediated increase in myocardial metabolic demands, as well as by ₂ adrenergic mediated vasodilation.Supported in Part by USPHS Grants HL 15416 and HL 17459     

The treatment of hypertension: New lamps for old?

Summary Meta-analysis of clinical trials does not help the clinician to treat individual patients. A general conclusion that the reduction of high blood pressure is beneficial has to be matched by specific information about the level of blood pressure that is acceptable and about the effect of particular doses of specific drugs. Results obtained from trials of old-fashioned antihypertensive drugs cannot confidently be extrapolated to modern agents. Sufficient data do not exist to encourage universal drug treatment for patients with mild hypertension.     

Capsular and ‘O’ serotype determinants of Bacteroides fragilis

Summary Forty-one strains ofBacteroides fragilis, 20 strains of otherBacteroides species and 14 strains of other genera were examined by the indirect immunofluorescent assay (IFA) using anticapsular serum. The sixty-oneBacteroides strains were O serotyped by direct agglutination tests using absorbed antisera raised against 23 strains, each with a different O antigenic determinant. All 41B. fragilis strains tested were positive by IFA with the anticapsular serum, but apart from one strain ofB. distasonis, none of the remaining 19 strains of other bacteroides, i. e.B. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus group andB. ureolyticus, and none of the 14 other bacterial species examined were positive. The majority of strains of saccharolytic bacteroides tested reacted with one of the 23 O antisera and were designated as a specific O serotype; a fewBacteroides strains had multiple agglutination reactions indicating the presence of multiple antigenic determinants. All O serotypes gave positive IFA tests with their homologous O antisera. Common capsular determinants and O antigenic determinants appear to exist on the same strains ofB. fragilis. Serological typing ofB. fragilis and related species would be useful in epidemiological studies.

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Kapsel- und O-Determinanten von Bacteroides fragilis

Zusammenfassung 41 Stämme vonBacteroides fragilis, 20 Stämme andererBacteroides-Spezies und 14 Stämme anderer Genera wurden unter Verwendung von Kapsel-Antiserum mit dem indirekten Immunfluoreszenztest (IFA) untersucht. Die O-Serotypisierung der 61Bacteroides-Stämme erfolgte mit dem indirekten Agglutinationstest; dabei wurden absorbierte Antiseren gegen 23 Stämme verwendet, von denen jeder eine unterschiedliche O-Determinante aufwies. Alle untersuchten 41 Stämme vonB. fragilis waren im IFA mit Kapsel-Antiseren positiv; hingegen war mit Ausnahme eines Stammes vonB. distasonis keiner der übrigen Stämme andererBacteroides-Spezies positiv, das heißt der GruppeB. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus undB. ureolyticus; von den anderen geprüften 14 Bakterienspezies war ebenfalls keine positiv. Die Mehrzahl der Stämme der untersuchten saccharolytischenBacteroides reagierte mit einem der 23 O-Antiseren und wurde einem spezifischen O-Serotyp zugeordnet; einigeBacteroides-Stämme wiesen mehrfache Agglutinations-reaktionen auf, was für das Vorliegen mehrerer Antigendeterminanten spricht. Bei denselben Stämmen vonB. fragilis scheinen gemeinsame Kapsel- und O-Antigendeterminanten vorzukommen. Für epidemiologische Untersuchungen dürfte die Serotypisierung vonB. fragilis und verwandten Spezies von Nutzen sein.

     

Macrophages enhance binding of beta-VLDL and cholesterol ester accumulation in cultured aortic smooth muscle cells

Summary The effect of macrophages on the uptake of -very low-density lipoprotein (-VLDL) by smooth muscle cells (SMC) expressing different morphological phenotypes was examined in culture. The SMC were grown alone and in co-culture with macrophages for four days, then incubated with different concentrations of¹²⁵I--VLDL for 3 h at 4°C or with 75 ug/ml -VLDL for 24h at 37°C. The binding of -VLDL to SMC at 4°C was enhanced in the presence of macrophages irrespective of the phenotype expressed by SMC. This occurred through modification of the lipoprotein, since binding of re-isolated macrophage-conditioned -VLDL to SMC was 12.5 times that of fresh -VLDL. This modified form of -VLDL competed with fresh -VLDL for binding to SMC. Binding was inhibited in the presence of probucol, suggesting that an oxidative mechanism may be involved.The presence of macrophages also enhanced the accumulation of -VLDL-derived cholesterol in SMC. While most of this is a consequence of the enhanced binding, macrophages may also act directly on SMC to increase cholesterol accumulation, since the activity of acid cholesterol ester hydrolase and neutral cholesterol ester hydrolase in SMC was reduced in the presence of macrophages.     

Morphologie und klinische Bedeutung des meningealen Hämangiopericytoms

Zusammenfassung Hämangiopericytome der Meningen sind selten. Es wird über drei derartige Tumoren mit einem jeweils über 10 Jahre währenden Beobachtungszeitraum berichtet. Primär erfolgte die Klassifizierung in allen Fällen als Meningeom (1mal gefäßreich, 2mal angioblastisch). Erst nach z.T. mehrfachen Rezidiven sowie extracranieller Metastasierung in zwei Fällen wurden die Diagnosen revidiert und die Tumoren als Hämangiopericytom aufgefaßt.Morphologisch zeigen angioblastisches Meningeom und Hämangiopericytom der Meningen auffällige Gemeinsamkeiten. Das fundamentale Baumuster beruht auf der blastomatösen Vermehrung capillärer Blutgefäße mit normaler Endothelauskleidung, extracapillär proliferierter mesenchymaler Zellen vom Typ der Pericyten und einem intercellulären Netzwerk reticulärer Fasern. Die erhobenen licht- und elektronenmikroskopischen Befunde zeigen nicht die typischen Merkmale eines Meningeoms. Da zudem Klinik und Wachstumsverhalten von angioblastischem Meningeom und Hämangiopericytom der Meningen vergleichbar sind, erscheint es gerechtfertigt, diese Tumoren als einheitliche Geschwulstform mit gemeinsamer Histogenese anzusehen. Wegen der bekanntermaßen hohen Rezidiv- und Metastasierungsrate des Hämangiopericytoms einerseits — im Gegensatz zu der Gutartigkeit der üblichen Meningeome andererseits — halten wir es für sinnvoll, diese meningealen Tumoren einheitlich als Hämangiopericytom der Meningen zu bezeichnen, um hinsichtlich des therapeutischen Vorgehens und prognostischer Aussagen die Besonderheit dieser meningealen Tumorform hervorzuheben.

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Morphology and clinical significance of the meningeal hemangiopericytoma

Summary Hemangiopericytomas of the meninges are rare tumors. Three tumors of this type with a course over more than 10 years each are reported. All three tumors were primary diagnosed as meningiomas (one: vascular, two angioblastic). The diagnosis was changed to hemangiopericytoma only then when recurrences and extracranial metastases had occurred. Morphologically, angioblastic meningioma and hemangiopericytoma of the meninges show striking common features. The principal pattern bases on the blastomatous increase of capillary blood vessels lined by a normal endothelium, extracapillary proliferation of pericyte-like mesenchymal cells and an intercellular network of reticulin fibres. Light- and electron microsopic findings do not demonstrate the characteristics of a meningioma. Furthermore, clinical data and growth pattern of angioblastic meningioma and hemangiopericytoma of the meninges are well comparable. Therefore, it seems to be justified to interpret these tumors as a tumor entity with identical histogenesis. It is well known that hemangiopericytomas frequently recur and metastasise. On the other hand, meningiomas are usually benign. For those reasons we suggest that these tumors should be uniformly classified as hemangiopericytoma of the meninges in order to stress the significance of these particular tumors of the meninges regarding their treatment and behaviour.

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Herrn Prof. Dr. med. Dr. phil. Rudolf Janzen gewidmet.     

Untersuchungen zur Wechselwirkung zwischen aromatischen Kohlenwasserstoffen und Aminen mit Desoxyribonucleinsäure

Zusammenfassung Zur Untersuchung der Wechselwirkung mit DNA wurden Lösungen von hochmolekularer Kalbsthymus-DNA mit Dimethylformamid-Lösungen von zwölf krebserzeugend unwirksamen und wirksamen aromatischen Kohlenwasserstoffen und Aminen versetzt. Anschließend wurden die Lösungen dialysiert, mit organischen Lösungsmitteln extrahiert und zentrifugiert. Aus den UV-Spektren der Lösungen wurden bestimmt: a) aus den Banden der Aromaten oberhalb 300 m die Menge an gebundener Verbindung, b) die Extinktion bei 260 m als Maß für die in Lösung vorhandene DNA und durch Verfolgung der Extinktion bei Temperaturerhöhung der hyperchrome Effekt und der Schmelzpunkt der DNA. Beziehungen zwischen den erhaltenen Daten und der krebserzeugenden Wirksamkeit der Verbindungen wurden nicht gefunden. Ohne Effekt waren ferner Pyridino-[2,3:3,4]-phenoxazon-(2) und das Follikelhormon Östradiol(3,17 ). Bestätigt wurde die Wechselwirkung mit DNA für die Mutagene Proflavin und Acridinorange. Auffallend ist eine deutliche Erhöhung des Schmelzpunktes der DNA durch N-Phthalyl-glutaminsäure-imid.

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Summary Solutions of high molecular calf-thymus-DNA were mixed with dimethyl formamide solutions of 12 cancerogenic inactive and active aromatic hydrocarbons and amines in order to study the reciprocal effect with DNA. The solutions were then dialyzed, extracted with organic solvents, and centrifuged. From the UV spectra of the solutions the following were determined: (a) the amount of bound compounds from the bands of aromatics above 300 m; (b) the extinction at 260 m as a measure of the DNA present in the solution. By following the extinction with increases in temperature the hyperchrome effect and the melting point of DNA were determined. Relationships between the data obtained and the cancerogenic activity of the compounds were not found. In addition, pyridino-[2,33,4]-phenoxazon-(2) and the follicle hormone estradiol-(3,17 ) were without effect. The reciprocal effect of DNA with the mutagens, proflavin and acridine orange, was confirmed. A distinct increase of the melting point of DNA by means of N-phthalyl-glutaminic acid-imide was striking.

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Herrn Prof. Dr. K. H. Bauer zum 75. Geburtstag gewidmet.     

Computer simulation of the propagation of contrast medium in a coronary artery during one cardiac cycle

In some angiographic methods for measurement of mean coronary flow in ml/min, a threshold is applied to concentration-distance curves obtained from a constant rate injection by computing the intravascular contrast medium concentration along the main coronary branches. If the shape of the velocity profile would remain parabolic throughout the cardiac cycle, the correct threshold value would be 50% of the concentration at the injection site. But, coronary flow being strongly pulsatile, the shape of the velocity profile must be expected to vary appreciably within the cardiac phase. In order to investigate if a single, appropriate threshold value nevertheless exists for a great variety of coronary flow pulses and velocity profiles, the spreading of contrast medium injected continuously in a tube perfused by a time varying flow Q(t) was studied by computer simulation. While the particular time courses of flow and velocity profile appear to be of secondary importance, the ratio injection rate to peak coronary flow has a major impact. If it is equal to or greater than 1, a threshold value of 47% is the best choice. If the ratio is markedly less than 1, no appropriate threshold exists and use of the 47% threshold will result in considerable flow underestimations. This was fully confirmed by measurements of absolute coronary flow performed in patients.     

A monoclonal antibody-linked immunoassay for hemoglobin H disease

Summary A murine monoclonal antibody (mAb) was generated that recognizes hemoglobin (Hb) H, the tetrameric form (₄) of human -globin chains. The antibody ₄-1 (1, ) does not react with Hbs A, F, Bart's, or isolated chains, indicating that the antibody recognizes an epitope comprised of multiple chains. A simple, rapid, and sensitive enzyme immunoassay was established to detect and quantitate Hb H in hemolysates from subjects with Hb H disease. The globin level in these patients was also measured using the monoclonal antibody -1, which is specific for chains of Hb A₂. With these assays, 20 hemolysates from subjects with Hb H disease' ten from normal adults and ten from newborn babies were analyzed. The percent of Hb H ranged from 1.5% to 25% in Hb H patients. There was a significant average reduction (32%) in chains in these samples as compared with the normal average adult value. The decreased expresion of chains thus results in a reduction of the levels of normal Hbs A and A₂ and accumulation of ₄, causing Hb H disease.Work supported by NIH grant HLB-41544     

A case of anti-Jo1 myositis with pleural effusions and pericardial tamponade developing after exposure to a fermented Kombucha beverage

The pathogenesis of the idiopathic inflammatory myopathies has been postulated to be an environmental trigger causing the expression of the disease in a genetically predisposed patient. We report a case of anti-Jo1 antibody-positive myositis which was associated with pleural effusions, pericardial effusion with tamponade, and mechanics hands, probably related to the consumption of a fermented Kombucha beverage. Kombucha mushroom, a symbiosis of yeast and bacteria, is postulated to be the trigger for our patients disease owing to the proximity of his symptoms to the consumption of the Kombucha beverage.Abbreviations ALT Alanine transferase - AST Aspartate aminotransferase - CPK Creatinine phosphokinase     

Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the ₃-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the ₂-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1–10 mol/kg) and clenbuterol (0.01–1 mol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1–3 mol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10–100 mol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective –adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a ₃-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mol/kg) nor clenbuterol (100 mol/kg) modified the acid secretion induced by histamine. These data suggest that ₃ adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.     

Ultrasonic tissue characterization in patients with dilated cardiomyopathy: comparison with findings from right ventricular endomyocardial biopsy

Aim: The clinical usefulness of integrated backscatter (IB) imaging was compared with right ventricular endomyocardial biopsy for assessing myocardial damage in patients with dilated cardiomyopathy (DCM). Methods: We examined 15 patients with DCM and 20 healthy controls. In addition to the conventional M-mode echocardiographic parameters, we determined the cyclic variation in IB values (CV-IB) obtained from parasternal short axis views of the left ventricle just under the transducer for both the interventricular septum (IVS) and the left ventricular posterior wall (PW). The per cent fibrosis area (%) and the transverse diameter of myocytes (m) were measured in right ventricular endomyocardial biopsy specimens by computer image analysis. To analyze the relationship between pathological findings and CV-IB, we divided patients into four subgroups on the basis of the pathological characteristics of endomyocardial biopsy specimens as follows: degeneration dominant group (n=5), fibrosis dominant group (n=5), dilated phase hypertrophic cardiomyopathy (n=2), and mixed type (n=3). Results: CV-IB in the IVS and the PW was lower in patients with DCM (8.8 ± 2.9, 8.3 ± 2.7dB, respectively) than in normal subjects (14.4 ± 2.9, 13.6 ± 2.6dB, respectively). Biopsy findings showed a mean per cent fibrosis area of 24.0 ± 12.3%, and a mean myocyte diameter of 14.3 ± 2.9m in patients with DCM. CV-IB was correlated with both of these findings: per cent fibrosis area (r=–0.56 in IVS, r=–0.56 in PW) and myocyte diameter (r=0.67 in IVS, r=0.71 in PW). CV-IB was decreased in all DCM subgroups compared with normal subjects, but there was no significant difference between subgroups. Conclusions: CV-IB was correlated with both the extent of fibrosis in myocardial tissue and the myocyte diameter. These findings suggest that ultrasonic tissue characterization is a good indicator of the severity of fibrosis and myocyte atrophy in patients with DCM.