Masayuki Ogami

Neutrophil Infiltration of Culprit Lesions in Acute Coronary Syndromes

Background—Neutrophils in unstable atherosclerotic lesions have not received much consideration, despite accumulating evidence suggesting a link between systemic inflammation and acute coronary syndromes. Methods and Results—Coronary artery segments were obtained at autopsy from 13 patients with acute myocardial infarction (AMI); 8 had a ruptured and 5 an eroded plaque. Patients (n=45) who had died of noncardiovascular diseases served as reference. Atherectomy specimens were obtained from 35 patients with stable angina pectoris (SAP) and from 32 patients with unstable angina pectoris (UAP). Antibodies against CD66b, elastase, myeloperoxidase, and CD11b identified neutrophils; CD10 identified neutral endopeptidase (NEP). CD66b-positive and NEP-positive neutrophils were counted and expressed as a number per square millimeter of tissue. All specimens with plaque rupture or erosion showed distinct neutrophil infiltration; the number did not differ between ruptured and eroded plaques. However, the number of NEP-positive neutrophils was significantly higher (P <0.0001) in ruptured plaques than in eroded plaques. UAP patients showed neutrophils in 14 of 32 culprit lesions; in SAP only 2 of 35 lesions contained neutrophils. The number of neutrophils and NEP-positive cells in patients with UAP was significantly higher (neutrophils, P <0.0005; NEP-positive cells, P <0.005) than in patients with SAP. Conclusions—The observations suggest that neutrophil infiltration is actively associated with acute coronary events. The high number of NEP-positive neutrophils in ruptured plaques, compared with eroded plaques, may reflect differences in the underlying pathophysiological mechanisms.

Telomere Shortening in Human Coronary Artery Diseases

Background—Increased cell turnover in response to injury is considered to be important in the development of atherosclerotic plaques. Telomere shortening has been shown to be associated with cell turnover. We assessed the telomere length of human coronary endothelial cells to clarify whether there is a relationship between telomere shortening and coronary artery disease (CAD). Methods and Results—Coronary endothelial cells were obtained from 11 patients with CAD who underwent autopsy and 22 patients without CAD who underwent autopsy by scraping off the luminal surface of coronary arteries. DNA extracted from the endothelial cells were blotted and hybridized with telomere-specific oligonucleotide ([TTAGGG]4). The hybridization signal intensity, which represented telomeric DNA content, was standardized with centromeric DNA content (T/C ratio) to estimate telomere length. The T/C ratios were significantly smaller (P <0.0001) in CAD patients than in age-matched non-CAD patients (CAD patients, 0.462±0.135; non-CAD patients, 1.002±0.212). In 6 individual CAD patients, the T/C ratio at the atherosclerotic lesion was significantly smaller (P <0.05) than that at the non-atherosclerotic portion. Conclusions—These findings suggest that focal replicative senescence and telomere shortening of endothelial cells may play a critical role in coronary atherogenesis and CAD.

Pathophysiological role of oxidized low-density lipoprotein in plaque instability in coronary artery diseases

Oxidized low-density lipoprotein (ox-LDL) is considered to play a key role in the genesis of inflammatory processes in atherosclerotic lesions. It has also been shown that LDL isolated from patients with diabetes mellitus (DM) has an enhanced susceptibility to oxidation. Recently, a sandwich ELISA method for measurement of plasma ox-LDL levels has been developed. To elucidate the role of ox-LDL in plaque instability in coronary artery disease, we measured the plasma ox-LDL levels in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP), and moreover assessed whether a relationship is present between plasma ox-LDL levels and DM. We also measured the plasma ox-LDL level in a patient who died of AMI, thus enabling us to study the presence of ox-LDL and CD 36, which is one of the ox-LDL receptors, in the culprit lesion. Plasma ox-LDL levels were measured in 210 patients (AMI: 70, UAP: 70, SAP: 70), and in 55 control subjects. Plasma ox-LDL levels in AMI patients were significantly higher than in UAP patients (P<.0001), SAP patients (P<.0001), or controls (P<.0001). In the UAP group, plasma ox-LDL levels in patients with DM were significantly higher than those without DM (P<.005). The autopsied patient who died of AMI revealed an increased plasma level of ox-LDL, and immunohistochemically, the culprit coronary lesion contained abundant macrophage-derived foam cells, showing distinct positivity for ox-LDL and CD 36. These results strongly suggest an important role for ox-LDL in the genesis of plaque instability in human coronary atherosclerotic lesions.

Mast cell chymase expression in Helicobacter pylori-associated gastritis

Aims:  To study the role of mast cell chymase in the inflammatory processes of human chronic gastritis. Experimental studies have shown that mast cell chymase stimulates inflammatory cell accumulation, and contributes to angiotensin II formation.

Effects of alanine in patients with advanced primary biliary cirrhosis: preliminary report

When rats given D-galactosamine are then treated with the glucogenic amino acid alanine, their alanine aminotransferase (ALT) activity, total bilirubin level, and survival rate improve compared with when other amino acids are used. Here, we report a preliminary study of the clinical and pharmacological effects of alanine given to three patients with primary biliary cirrhosis (PBC). The patients were jaundiced and were in the end-stage of the disease. The treatment they had been receiving was continued while they were given 18 g of alanine per day for a planned 8 weeks. For all three patients, test results for total bilirubin, alkaline phosphatase, and ALT decreased by 25% or more from the base line at some time during treatment. The arterial ketone-body ratio increased. Two of the patients reported that their itching and fatigue lessened. Except for one patient given a second course, who reported nausea, adverse effects were not found. In end-stage PBC, alanine administration decreased the total bilirubin level and improved symptoms, so this compound may decrease jaundice in this disease. A long-term study of a larger group of patients is needed.

A 56 Year-Old Female with Congenital Hepatic Fibrosis Diagnosed by Laparoscopy

Abstract: We describe a 56‐year‐old woman with congenital hepatic fibrosis. Blood tests and liver scanning with Tc‐99m‐labelled galactosyl human serum albumin revealed mild liver dysfunction. Per‐rectal portal scintigraphy with iodine‐123 iodoamphetamine showed severe abnormalities in the portal circulation, and the portal pressure measured during percutaneous transhepatic portography was high (350 mmH2O). Idiopathic portal hypertension was suspected. Laparoscopy disclosed diffuse, intense dendritic white markings around the liver. Congenital hepatic fibrosis was confirmed on histologic examination of a biopsy specimen obtained during laparoscopy. In summary, we report a rare and relatively elderly case of CHF, in which laparoscopy was useful in the diagnosis. (Dig Endosc 1999; 11: 174–178)