Ciliated respiratory-like epithelium forming cystic conjunctival lesions in a patient with Stevens-Johnson syndrome.

A woman with severe cicatricial conjunctival changes secondary to allopurinol-induced Stevens-Johnson syndrome developed bilateral palpebral conjunctival cysts. Pathologic examination of these lesions revealed respiratory-like pseudostratified ciliated epithelium in the walls of several cysts of one eye. To our knowledge, this is the first report of this phenomenon.     

Adrenocorticotropin receptors: functional expression from rat adrenal mRNA in Xenopus laevis oocytes.

The adrenocorticotropin (ACTH) receptor, which binds corticotropin and stimulates adenylate cyclase and steroidogenesis in adrenocortical cells, was expressed in Xenopus laevis oocytes microinjected with rat adrenal poly(A)+ RNA. Expression of the ACTH receptor in individual stage 5 and 6 oocytes was monitored by radioimmunoassay of ligand-stimulated cAMP production. Injection of 5-40 ng of adrenal mRNA caused dose-dependent increases in ACTH-responsive cAMP production. These were detected at 48 h and reached a maximum 72 h after microinjection of 20-40 ng of adrenal mRNA. In response to 1 microM ACTH, total cAMP production increased within 2.5 min and reached half-maximal and maximal levels (5-fold greater than basal) at 10 and 75 min, respectively, and then remained elevated for up to 5 h. Extracellular cAMP levels were much lower but showed prominent linear increases from almost undetectable levels, with 70- and 150-fold increases evident at 1 and 2 h, respectively. The half-maximal concentration (ED50) for stimulation of cAMP formation was 5 x 10(-8) M ACTH-(1-24); the ED50 for ACTH-(1-17) was 5 x 10(-7) M, and no response was observed with ACTH-(1-10). Size fractionation of rat adrenal poly(A)+ RNA by sucrose density-gradient centrifugation revealed that mRNA encoding the ACTH receptor was present in the 1.1- to 2.0-kilobase fraction. These data indicate that ACTH receptors can be expressed from adrenal mRNA in Xenopus oocytes and are fully functional in terms of ligand specificity and signal generation. The extracellular cAMP response to ACTH is a sensitive and convenient index of receptor expression. This system should permit more complete characterization and expression cloning of the ACTH receptor.     

Promoting clinically effective practice: general practitioners' awareness of sources of research evidence

BACKGROUND: Practitioners are being encouraged to base their clinical practice on research evidence. In order to do this, they must be aware of and use the sources of evidence. METHODS: A questionnaire survey was undertaken to establish GPs' awareness of research evidence in their clinical practice and, in fundholding practices, its influence on purchasing plans. Questionnaires were sent to 360 lead fundholders in North Thames Region and 440 of a random sample of the remaining general practitioners in the region for comparison. RESULTS: Questionnaires were returned by 62% of lead fundholders and 63% of GPs in the random sample. There was limited use of the electronic sources of clinical effectiveness. There was greater reported awareness of published sources of research evidence and fundholding GPs were significantly more likely to have referred to publications summarizing research evidence. CONCLUSIONS: GPs seem to make more use of published clinical effectiveness sources than the electronic databases. Consequently, they need educational and technical support if they are to make full use of the available sources of research evidence available in other media.      

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

Autoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera of patients with autoimmune liver disorders. Liver-infiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with AI-CAH or PBC but not chronic viral hepatitis secreted anti-ASGPR antibodies in vitro. In this study we characterized the influence of liver-infiltrating T cells on the secretion of ASGPR-specific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with AI-CAH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibody-secreting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supernatants and showed a proliferative response to ASGPR. T cell-depleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+CD8- liver-infiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous anti-ASGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8- and two CD4-CD8+ T cell clones non-responding to ASGPR provided this help for antibody secretion. Anti-ASGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclonal-activating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGPR-specific antibodies. This help can be provided by ASGPR-responsive T helper cells via cellular interactions.     

Zur Pathogenese der sogenannten malignen Hypertonie

Zusammenfassung Die Polyätiologie verschiedener Grundkrankheiten und moderne therapeutische Möglichkeiten zur Beseitigung des malignen Verlaufes einer arteriellen Hypertension lassen den Ersatz des Begriffes maligne Hypertonie durch die Bezeichnung akzelerierte Hypertonie angebracht erscheinen. Bis heute ist die Pathogenese einer sog. malignen Hypertonie nicht geklärt. Ein endgültiger Beweis für die Immunpathogenese der Akzeleration einer Hypertonie steht noch aus. Für den malignen Verlauf einer Hypertonie kann eine Stimulierung des Renin-Angiotensin-Aldosteronsystems nicht direkt verantwortlich gemacht werden. Eine solche Stimulierung wird umgekehrt nicht durch eine nekrotisierende Arteriolitis ausgelöst, da sich diese Veränderung unabhängig von einer arteriellen Hypertonie entwickeln kann. Vermutlich sind an der Regulierung der Reninfreisetzung nicht nur intrarenale Chemoreceptoren beteiligt. Der Nachweis einer vermehrten Aktivität von Renin und Erythropoetin im peripheren Plasma bei Patienten mit akzelerierter Hypertonie ist kein Grund zur Annahme, die Abgabe beider Stoffe würde durch einen gemeinsamen Mechanismus gesteuert. Andere Prinzipien, wie antihypertensive renomedulläre Faktoren, Hypervolämie usw., spielen bei der Akzeleration einer arteriellen Hypertonie keine erkennbare Rolle.

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Summary Because of the polyetiology of various basal disorders and of modern therapeutic possibilities to abolish the malignant course of an arterial hypertension it is proposed to replace the term malignant hypertension by the definition accelerated hypertension. The pathogenesis of the so-called malignant hypertension is obscure at this time. There is no proof of an immunological mechanism involved with the acceleration of hypertensive diseases. Stimulation of the reninangiotensin-aldosterone system is not directly due to the malignant course of hypertension. Such a stimulation, in turn, is not caused by a necrotizing arteriolitis, since this structural vascular damage can occur sometimes without hypertension. Presumably the control of renin release is more complicated than generally discussed and not only mediated by intrarenal chemoreceptors. Inspite of concomitant increase of both renin and erythropoietin activities in peripheral plasma of many patients with accelerated hypertension, it is suggested, that the secretion of these substances is directed by different mechanisms. Other factors, i.e. a renomedullary antihypertensive principle or hypervolemia, do not play any significant role in the acceleration of arterial hypertension.

     

Vergleichende Untersuchungen der enzymatischen Bestimmung von Harnsäure mit einer einfachen colorimetrischen Methode

Zusammenfassung Es werden zwei Verfahren der enzymatischen Harnsäurebestimmung miteinander verglichen: der als Standard-Referenz-Methode gebräuchliche Uricase-UV-Test und eine spezifische colorimetrische Uricase-Katalase-Methode nach Kageyama (1971). Die mit dem Farbtest erhaltenen Werte korrelieren hervorragend (r=0,9976) mit denen, die sich bei Anwendung der UV-Methode ergeben. Die neue Methode weist einige wesentliche Vorteile auf: Die Reproduzierbarkeit ist besser und der Arbeitsaufwand geringer als mit dem UV-Test. Lipämische, leicht bis mäßig hyperbilirubinämische oder leicht hämolytische Seren sind ohne vorherige Enteiweißung verwertbar. Die colorimetrische Methode kann als brauchbares, einfaches und zuverlässiges Routine-Verfahren zur Harnsäurebestimmung in klinischen Laboratorien empfohlen werden.