Serial alterations of beta-adrenergic signaling in dilated cardiomyopathic hamsters: possible role of myocardial oxidative stress.

BACKGROUND: The relationship between enhanced myocardial oxidative stress and impaired beta-adrenergic signaling remains to be characterized during the development of dilated cardiomyopathy. METHODS AND RESULTS: Alterations in myocardial oxidative stress and beta-adrenergic signaling, as well as left ventricular (LV) functional and structural changes, were evaluated during the development of cardiomyopathy in TO-2 hamsters; F1B hamsters served as controls. LV dysfunction was first apparent at 8 weeks of age and deteriorated thereafter in the TO-2 hamsters. At 32 weeks, the animals exhibited heart failure with an increased plasma norepinephrine concentration. Cardiac myolysis, as demonstrated by elevated plasma concentration of cardiac troponin T, peaked at 8 weeks. The glutathione redox ratio revealed increased oxidative stress in the LV myocardium in TO-2 hamsters even at 4 weeks and became manifest after 8 weeks. The hearts of TO-2 hamsters had significantly reduced superoxide dismutase activity from 8 weeks onward compared with control hamsters. However, glutathione peroxidase activity was unchanged at any time point. The LV functional response to isoproterenol was markedly reduced at 8 weeks, without any apparent changes in the amount of beta-adrenergic signaling molecules, and it deteriorated thereafter. Adenylyl cyclase activity was significantly decreased, despite increased amounts of both G(s) alpha mRNA and protein, in the LV myocardium at 18 weeks. CONCLUSIONS: Myocardial oxidative stress is actually enhanced in the initial development of LV dysfunction. Both activation of myocardial oxidative stress and impairment of beta-adrenergic signaling become prominent at the stage of severe LV dysfunction. Myocardial oxidative stress may be involved in the development of beta-adrenergic desensitization.     

Regression of superficial gastric MALT lymphoma with unsuccessful eradication therapy forHelicobacter pylori infection

A 51-year-old man had a reddish flat granular lesion in the stomach on endoscopic examination. Histology of biopsied specimen confirmed the diagnosis of low-grade B-cell gastric lymphoma of mucosaassociated lymphoid tissue (gastric MALT lymphoma) and simultaneous infection withHelicobacter pylori. He was given antibiotic treatment. Five weeks later, endoscopy and histology of biopsied specimen showed eradication ofH. pylori, and the tumor had regressed. Six months later,H. pylori reemerged, but the tumor had not recurred. After the second antibiotic therapy,H. pylori has been eradicated. The lymphoma has been in remission for 14 months.     

Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients

Histopathologic examination was performed in 20 patients undergoing antemortem coronary angioplasty. Thirty-four lesions were dilated and the interval between coronary angioplasty and death ranged from several hours to 4 years. Intimal proliferation of smooth muscle cells, as a major cause of restenosis, was observed in 83% to 100% of 28 lesions examined 11 days to 2 years after coronary angioplasty. In 20 lesions examined within 6 months, proliferating smooth muscle cells were predominantly of the synthetic type and there was abundant extracellular matrix substance chiefly composed of proteoglycans. In eight lesions examined between 6 months and 2 years, contractile type smooth muscle cells were dominant and extracellular matrix was composed chiefly of collagen. In three lesions examined after 2 years, evidence of antemortem coronary angioplasty was hardly identifiable and these lesions were almost indistinguishable from conventional atherosclerotic plaque. These temporal changes in histologic pattern provide a pathologic background for clinical reports that restenosis is predominantly found within 6 months after coronary angioplasty. Morphometric analysis revealed that the extent of intimal proliferation was significantly greater in lesions with evidence of medial or adventitial tears than in lesions with no or only intimal tears.     

Fibrolamellar hepatocellular carcinoma: report of a case

We report a case of fibrolamellar hepatocellular carcinoma, which occurred in a 58-year-old man with normal liver function. Preoperative ultrasonography, computed tomography and magnetic resonance imaging depicted a large tumor in the left lateral segment, which was compatible with the typical radiological features of fibrolamellar hepatocellular carcinoma. He underwent left lobectomy and no lymphadenopathy or distant metastasis was demonstrated. Macroscopic findings of the resected liver demonstrated a well-defined whitish-yellow tumor with a central scar. Microscopic findings of the tumor showed cords of tumor cells, which were surrounded by abundant collagenous fibrous tissue arranged in a lamellar distribution. He has been doing well for approximately one year since the surgery without any signs of recurrence. In addition, we discuss the clinicopathological features of fibrolamellar hepatocellular carcinoma based on a review of 22 Japanese patients who have been previously reported.     

Increased serum IgE level and interleukin-4 release from cultured lymphocytes from a patient with adult onset Still''s disease.

OBJECTIVE--To evaluate the relationship between high serum levels of IgE and the release of interleukin-4 (IL-4) from cultured lymphocytes of a patient with adult onset Still's disease. METHODS--IL-4 concentrations in plasma and culture from inactivated peripheral blood mononuclear cells were assessed by enzyme immunoassay during febrile episodes and remission. RESULTS--A high level of IL-4 was detected by enzyme immunoassay in the peripheral blood mononuclear cells cultured from the patient. These seemed to correspond with a febrile episode and a high serum IgE concentration. CONCLUSION--Increased serum IgE concentrations during a febrile episode are rare in patients with adult onset Still's disease, but the relationship between the high levels of serum IgE and IL-4 in cultured lymphocytes may provide clues to pathogenesis of the condition.     

Effects of hypertonic mannitol on renal function in open heart surgery

An extracorporeal bypass was performed in mongrel dogs for 2 hours with or without hypertonic mannitol infusions. In animals given mannitol, the plasma osmolality was elevated maximally to 344 +/- 7.1 mOsm/L and the urine volume was maintained well during bypass. A hypertonic mannitol solution was effective in maintaining the CPAH during and after bypass, but was not effective in minimizing the reduction in Ccr. When the mean arterial pressure during bypass was kept at 60 mmHg, the carbon filling rates in glomeruli showed the favorable effects of mannitol upon renal function, but no effects were observed at a mean arterial pressure of 80 mmHg. In 11 patients who had undergone a bypass lasting more than 2 hrs with mannitol infusions, the plasma osmolality reflected the serum mannitol level and reached 320 +/- 11.0 mOsm/L at 150 min of bypass. The mean urine volume was 5.0 +/- 3.3 ml/min/M2 during the bypass, which was about 7 times as great as before the bypass. The Ccr increased during the first 30 min of the bypass, but it fell to about one half of the initial value after 90 min of the bypass. It was concluded that a hypertonic mannitol solution is effective in maintaining the RPF and urine volume during and after the bypass and that it also preserved the glomerular perfusion even at a low arterial pressure.