An autopsy case of isolated eosinophilic coronary periarteritis: a limited form of Churg-Strauss syndrome or a new entity?

A 52-year-old man without a history of asthma or allergic diseases died of ventricular fibrillation early in the morning. His autopsy revealed no significant findings, except for a mild mural-thickening localized at the proximal region of the right coronary artery. Microscopic examination showed periarteritis with infiltration of numerous eosinophils in the adventitia. No significant vasculitis was found in any other organs. Based on the findings this seems to be the second reported case of isolated eosinophilic coronary periarteritis.     

Clinical evaluation of calcium metabolism in adult T-cell leukemia/lymphoma

To clarify the mechanism of development of hypercalcemia in adult T-cell leukemia/lymphoma (ATLL), ten patients with a serum creatinine level less than 177 mumol/L (2 mg/dL) were examined. Although hypercalcemia was seen in only four (40%) of these patients, four of six normocalcemic patients showed hypercalciuria (greater than 5 mmol/d [greater than 200 mg/24 h]). All hypercalcemic patients exhibited high nephrogenous cyclic adenosine monophosphate (NcAMP) levels in the face of low-normal immunoreactive parathyroid hormone and reduced serum 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration. Half of the hypercalciuric patients with normocalcemia also showed high NcAMP and reduced serum 1,25(OH)2D levels. Furthermore, the changes in NcAMP and serum 1,25(OH)2D concentration closely paralleled the development of hypercalcemia and hypercalciuria in two patients. These results are reminiscent of the syndrome of humoral hypercalcemia of malignancy and suggest that derangements in calcium metabolism develop by a similar mechanism in patients with ATLL. The present data also indicate the importance of the measurement of urinary calcium excretion for early detection and prevention of fatal hypercalcemia in patients with ATLL.     

The role of Ca2+ release from sarcoplasmic reticulum in the regulation of sinoatrial node automaticity

Summary The role of Ca²⁺ release channels in the sarcoplasmic reticulum in modulating physiological automaticity of the sinoatrial (SA) node was studied by recording transmembrane action potentials and membrane ionic currents in small preparations of the rabbit SA node. Ryanodine, which modifies the conductance and gating behavior of the Ca²⁺ release channels, was used to block Ca²⁺ release from the sarcoplasmic reticulum. Superfusion of 1-mM ryanodine decreased the spontaneous firing frequency as well as the maximal rate of depolarization of the SA, and these reductions reached a steady state within approximately 5min. The action potential recordings revealed that the latter part of diastolic depolarization was depressed and that the take-off potential became less negative. This suggested that the negative chronotropic effect of ryanodine resulted from the blockade of physiological Ca²⁺ release from the sarcoplasmic reticulum. In voltage clamp experiments, using double-microelectrode techniques, ryanodine did not markedly reduce the Ca²⁺ current (I_Ca) but decreased the delayed rectifying K+ current (I_K), the steady-state inward current (I_ss), and the hyperpolarization-activated inward current (I_h). These observations suggest that, even when the function of Ca²⁺ channels in the cell membrane is normally maintained, depression of Ca²⁺ release channels in the sarcoplasmic reticulum would prevent sufficient elevation of the Ca²⁺ concentration in SA node cells for the activation of various ionic currents, and, thus adversely affect the physiological automaticity of this primary cardiac pacemaker.     

Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide.

Endothelin is a potent vasoconstrictor/pressor peptide, which we recently characterized from the conditioned culture medium of porcine aortic endothelial cells. We report here the cloning and partial sequencing of the rat endothelin gene. The nucleotide sequence predicted a 21-residue peptide similar to, but distinct from, porcine endothelin; 15 residues of rat endothelin were identical and 3 residues were substitutions by chemically similar amino acid residues to those in the porcine peptide. Synthetic rat endothelin was then prepared according to its deduced amino acid sequence. This synthetic peptide had (i) potent vasoconstrictor activity in the rat aortic strip and in perfused rat heart and (ii) a characteristically long-lasting in vivo pressor activity by intraaortic bolus injection in the conscious rat.     

Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways

Nuclear protein IRF-1 (interferon regulatory factor 1) was earlier shown to bind to cis-acting regulatory elements present on interferon (IFN)-alpha/beta genes and some IFN-inducible genes. Here we show that in both human FS-4 and murine L929 cells, steady-state levels of IRF-1 mRNA were increased by treatment with tumor necrosis factor (TNF), interleukin 1 (IL-1), poly(I).poly(C), or IFN-beta. IRF-1 mRNA induction was also demonstrated in cells treated with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, but not with epidermal growth factor, dibutyryl-cAMP, or the adenylate cyclase activator forskolin. To determine whether stimulation of IRF-1 mRNA levels correlates with IFN-beta induction, we compared IRF-1 and IFN-beta mRNA levels in cells exposed to various stimuli. In L929 cells, treatment with poly(I).poly(C) under conditions that failed to induce significant levels of IFN-beta mRNA led to a very low induction of IRF-1 mRNA, but "priming" cells with IFN prior to the addition of poly(I).poly(C) greatly increased both IRF-1 and IFN-beta mRNAs. In FS-4 cells an increase in IFN-beta mRNA (examined by the polymerase chain reaction) was seen after treatment with TNF, IL-1, A23187, or poly(I).poly(C), but not with IFN-beta, epidermal growth factor, dibutyryl-cAMP, or forskolin. Thus, all treatments that increased steady-state levels of IFN-beta mRNA also enhanced IRF-1 mRNA levels. However, treatment with IFN-beta, which caused a marked stimulation in IRF-1 mRNA, failed to produce a detectable increase in IFN-beta mRNA. It appears that IRF-1 may be necessary but not sufficient for IFN-beta induction. The ability of TNF and IL-1 to increase both IRF-1 and IFN-beta mRNAs may be responsible for some similarities in the actions of TNF, IL-1, and the IFNs.     

Has Helicobacter pylori eradication for peptic ulcer been overrated?

Discovery of Helicobacter pylori has changed the life cycle of peptic ulcer disease (PUD). However, PUD does not completely disappear after elimination of H. pylori. Some ulcers recur even after successful eradication of H. pylori in non-users of non-steroidal anti-inflammatory drug (NSAID). In addition, the incidence of H. pylori-negative, non-NSAID PUD (idiopathic PUD) is reported to increase with time. Moreover, H. pylori-positive ulcers are not always H. pylori-induced ulcers because there are two paradoxes of the H. pylori myth: the existence of H. pylori-positive non-recurring ulcer and recurring ulcer after cure of H. pylori infection. Taken together, H. pylori is not the only cause of peptic ulcer disease. Therefore, it is still necessary to seriously consider the pathophysiology and the management of the ulcers, which may exist after elimination of H. pylori.