Fine-needle aspiration biopsy of hepatic papillary cystadenocarcinoma in Caroli's disease.

A case of papillary adenocarcinoma arising in Caroli's disease (CD) in a 25-yr-old woman is reported. The diagnosis of malignancy was made by ultrasound-guided, fine-needle aspiration biopsy (FNAB). As there were no metastasis, a liver transplant was performed and the diagnosis was histologically confirmed. Only 22 cases of malignant transformation of CD have been reported to date, all among middle-aged subjects (mean age: 52 yr) of both sexes. Most of these reported cases (83%) were found to be bile duct adenocarcinomas with occasional reports of hepatocellular and undifferentiated carcinomas. Our case is the youngest reported to date and the first to be diagnosed cytologically.     

Detection by ELISA of IgA and IgM antibodies in secretion and IgM antibodies in serum in primary lower respiratory syncytial virus infection

Twenty-six infants and children with primary lower RS virus infection, diagnosed by the detection of RS virus in nasopharyngeal secretion (NPS) by use of immunofluorescent antibody (FA) technique, were studied with respect to the presence of IgA and IgM antibodies. Samples of NPS and serum obtained during the first 3-4 months following the beginning of illness, were investigated. Employing a reverse ELISA technique, we found IgM antibodies in the acute, but not during the convalescent, phase of illness in NPS from 20 of the patients and in serum from 21 of the patients. The majority of the IgM antibody conversions observed occurred in NPS as well as in serum on days 5-8 following the illness. RS virus IgA antibodies, also detected by a reverse ELISA technique, were demonstrated in NPS in 22 of the patients, with antibody conversions being found in 19 of the patients on days 5-8 following the beginning of the illness. Two patients still had IgA antibodies in NPS approximately 3 months FSOI. By comparison, RS virus was detected in acute-phase NPS by double-antibody sandwich ELISA in 25 of the 26 patients investigated.     

Activation of ion transport by combined effects of ionomycin,forskolin and phorbol ester on cultured HT-29cl.19A human colonocytes

The differentiated clone 19A of the HT-29 human colon carcinoma cell line was used as a model to study the intracellular electrophysiological effects of interaction of the cAMP, the protein kinase C (PKC) and the Ca²⁺ pathways, (a) A synergistic effect between ionomycin and forskolin was observed. From intracellular responses it was concluded that the synergistic effect is caused by activation of an apical Cl^– conductance by protein kinase A and a basolateral K⁺ conductance by Ca²⁺. (b) A transient synergistic effect of ionomycin and the phorbol ester phorbol dibutyrate (PDB) was found. The decrease of the response appeared to be due to PKC-dependent inactivation of the basolateral K⁺ conductance. The synergism is caused by PKC-dependent increase of the apical Cl^– conductance and Ca²⁺-dependent increase of the basolateral K⁺ conductance. (c) The effects of carbachol and PDB were not fully additive presumably because of their convergence on PKC activation, (d) Forskolin and PDB, when added in this order, had a less than additive effect. Results of cell-attached patch-clamp studies, presented in the accompanying paper, showed a synergistic effect of forskolin and PDB on non-rectifying small-conductance Cl^– channels. Assuming that these channels are involved in the transepithelial responses it is suggested that forskolin and PDB induce a modulatory, synergistic increase of the apical Cl^– conductance when both pathways are activated simultaneously. (e) The HT-29cl.19A cells differ from T₈₄ cells in that the latter did not respond with an increase of the short-circuit current to addition of phorbol ester. This may be due to a very low expression of PKC.     

Isolated perfused rabbit colon crypts: stimulation of Cl− secretion by forskolin

The aim of this study was to characterize ion conductances and carrier mechanisms of isolated in vitro perfused rabbit colonic crypts. Crypts were isolated from rabbit colon mucosa and mounted on a pipette system which allowed controlled perfusion of the lumen. In non-stimulated conditions basolateral membrane voltage (V _b1) was –65±1 mV (n=240). Bath Ba²⁺ (1 mmol/ l) and verapamil (0.1 mmol/l) depolarized V _b1 by 21±2 mV (n=7) and 31±1 (n=4), respectively. Lowering of bath Cl^– concentration hyperpolarized V _b1 from –69±3 to –75±3 mV (n=9). Lowering of luminal Cl^– concentration did not change V _b1. Basolateral application of loop diuretics (furosemide, piretanide, bumetanide) had no influence on V _b1 in non-stimulated crypts. Forskolin (10^–6 mol/l) in the bath depolarized V _b1 by 29±2 mV (n=54) and decreased luminal membrane resistance. In one-third of the experiments a spontaneous partial repolarization of V _b1 was seen in the presence of forskolin. During forskolin-induced depolarization basolateral application of loop diuretics hyperpolarized V _b1 significantly and concentration dependently with a potency sequence of bumetanide > piretanide furosemide. Lowering bath Cl^– concentration hyperpolarized V _b1. Lowering of luminal Cl^– concentration from 120 to 32 mmol/l during forskolin-induced depolarization led to a further depolarization of V_b1 by 7±2 mV (n=10). We conclude that V_b1 of rabbit colonic crypt cells is dominated by a K⁺ conductance. Stimulation of the cells by forskolin opens a luminal Cl^– conductance. Basolateral uptake of Cl^– occurs via a basolateral Na⁺ : 2Cl^– : K⁺ cotransport system.     

Analysis of proliferating biliary epithelial cells in human liver disease using a monoclonal antibody against DNA polymeraseα

The proliferative activity and ultrastructural characteristics of proliferating biliary epithelial cells were analysed immunohistocytochemically in 39 biopsied liver specimens from patients with acute viral hepatitis, chronic hepatitis and liver cirrhosis using a monoclonal antibody against DNA polymerase (DNA-PA). In acute viral hepatitis with perivenular confluent necrosis, proliferation of typical bile ducts was found frequently in portal areas. In chronic aggressive hepatitis and cirrhosis, ductular proliferation of both typical and atypical forms was found in enlarged portal and periportal areas and in confluent necrotic areas. The number of proliferating biliary epithelial cells that stained positive for DNA-PA was small. There were very few positively stained cells in atypical bile ducts in confluent necrotic areas of cirrhosis. Atypical bile ducts seen in chronic aggressive hepatitis, cirrhosis and acute hepatitis with confluent necrosis were positively stained for both cytokeratins 8 and 19. In cirrhosis, the number of stained biliary epithelial cells in typical bile ducts was larger than the number of such cells in atypical bile ducts (P< 0.01). By electron microscopy, the cells positively stained for DNA-PA were mostly so-called clear cells with irregular nuclei containing coarse nucleoplasm, and a few small cells with scanty cytoplasm and few organelles.     

The juxtaglomerular apparatus in malignant hypertension of man

Summary Investigation of the behaviour of the renal Juxtaglomerular apparatus in 19 patients with malignant hypertension has shown that in kidneys fixed immediately after operation the Juxtaglomerular granulation index is twice as high as in autopsy kidneys. The formation of renin by the epitheloid cells begins with the appearance of osmiophilic substances in the region of the endoplasmic reticulum. The first stages of granule formation are small rhomboid particles in the Golgi cisternes, which aggregate to form bigger round or polymorphic granules in the Golgi area.In pathological conditions the substances synthesized may be set free and become active locally as a result of fibrinoid necrosis of the vascular wall. The rate of production is increased firstly by forcing rhe production of active agents in the preexistent epitheloid cells, secondly by transformation of the so-called bivalent cells and finally, by cell division.In accelerated hypertension the production of renin also takes place in nephrons whose glomeruli, tubules and macula densa, are damaged. There is a correlation between blood pressure elevation and the Juxtaglomerular granulation index.

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Zusammenfassung Untersuchungen über das Verhalten des juxtaglomerulären Zellkomplexes der Niere bei 19 Patienten mit maligner Hypertonie haben folgendes ergeben: In operativ gewonnenen und sofort fixierten Nieren ist der juxtaglomeruläre Granulationsindex doppelt so hoch wie in Nieren aus dem Sektionsgut. Die Reninbildung der epitheloiden Zellen beginnt mit dem Auftreten osmiophiler Substanzen im Bereich des endoplasmatischen Reticulums. Kleine rhomboide Gebilde in Golgizisternen sind Vorstufen von reifen Sekretgranula, die sich im Golgifeld zu größeren runden oder vielgestaltigen Sekrettropfen zusammenlagern.Unter pathologischen Bedingungen können infolge fibrinoider Gefäß- wandnekrosen Sekretsubstanzen lokal frei und lokal wirksam werden. Vermehrte Arbeitsleistung erfolgt zunächst durch Forcierung der Sekretproduktion in den präexistenten epitheloiden Zellen, sodann durch Transformierung sogenannter bivalenter Zellen und schließlich durch Zellneubildungen.Reninproduktion findet bei akzelerierter Hypertonie auch in solchen Nephronen statt, deren Glomerula und Tubuli samt Macula densa strukturell geschädigt sind. Es besteht eine Korrelation zwischen Höhe des Blutdruckes und Höhe des Granulationsindex.

     

Ionophore A23187 can mimick the changes in membrane permeability that occur during acetylcholine-stimulation of pancreatic acinar secretion

Acetylcholine (ACh) released from vagal terminals increases the permeability of the pancreatic acinar membrane to Na⁺ and Ca²⁺ ions. In this report, we compare the induced changes in intracellular Na⁺ and Ca²⁺ electrode potentials (E_Na and E_Ca) due to ACh-stimulation of acini with those observed during stimulation with the calcium ionophore, A23187, which mimicks the action of ACh on pancreatic secretion. Stimulation with ACh concentrations varying from 10^–8 to 10^–5 M and with A23187 concentrations of 10^–6 and 10^–5 M caused parallel increases in cytosolic Ca²⁺ and Na⁺ ([Ca]_i, [Na]_i). The magnitude of the increases in [Ca]_i and [Na]_i due to A23187-stimulation further indicate that when presented with a calcium challenge the acinar cells continue to regulate [Ca]_i close to physiological levels and suggest that the observed increases in ionized calcium could reflect much larger increases in complexed Ca²⁺. ACh-stimulation following removal of either extracellular Na⁺ or Ca²⁺ ions, eliminated the intracellular increases found when the removed ions is present, but did not affect the increases usually found with the other ion. The independence of the permeability changes to either the presence of Ca²⁺ or Na⁺ indicates the ACh-induced currents carried by Na⁺ and Ca²⁺ are also independent. The selective translocation of Na⁺ and Ca²⁺ during acetylcholine-stimulation in a manner analogous to the changes observed when ionophore A23187 was used as stimulus, indicates the ability of the activated acinar membrane to function as an ionophore.     

Faster gastric emptying for glucose-polymer and fructose solutions than for glucose in humans

Summary This study examined the rates of gastric emptying for water and 13 different carbohydrate-containing solutions in seven subjects, using conventional gastric intubation techniques. The rates of gastric emptying for water and a 10% glucose-polymer solution were also measured during 90 min of treadmill running at 75% of each subject's maximum oxygen consumption . At rest, 15% glucose-polymer (P) and fructose (F) solutions emptied more rapidly from the stomach and provided a faster rate of carbohydrate delivery than did a 15% glucose (G) solution (p<0.05). The G solutions showed a constant energy delivery rate of 3.3 kcal · min^–1; energy delivery from P and F solutions rose with increasing solution concentrations. The osmolality of the gastric aspirate predicted the rate of gastric emptying for all solutions (p<0.05) but overestimated rates of emptying for 10% and 15% P solutions and underestimated emptying rates for 10% and 15% F solutions. Exercise at 75% decreased the rate of gastric emptying of water but not of 10% P solutions. Thus the different rates of gastric emptying for different carbohydrate-containing solutions were not entirely explained by differences in osmolality. Furthermore, exercise may have different effects on the gastric emptying rates of water and carbohydrate solutions.