Relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with type 2 diabetes mellitus

Although oxidization of LDL is known to be a crucial step for atherosclerotic progression, the significance of oxidized HDL remains to be clarified. The purpose of this study was to determine the relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with diabetes. The subjects were outpatients with type 2 diabetes (n?=?163; median hemoglobin A1c, 6.9%). Activities of blood coagulation and fibrinolysis were evaluated by levels of thrombin–anti-thrombin complex (TAT) and plasmin–α2 plasmin inhibitor complex (PIC), respectively. Relationships of oxidized HDL with TAT and PIC were investigated by using linear regression analysis and logistic regression analysis. Oxidized HDL showed a significant inverse correlation with TAT and a marginally significant correlation with PIC (Spearman’s rank correlation coefficient: TAT, ??0.205 [p?<?0.01]; PIC, ??0.135 [p?=?0.087]). Prevalence of high TAT was significantly lower in the 3rd tertile group for oxidized HDL than in its 1st tertile (20.4 vs. 5.6%, p?<?0.05), and prevalence of high PIC was marginally significantly lower in the 3rd tertile group for oxidized HDL than in its 1st tertile (40.7 vs. 24.1%, p?=?0.099). In multivariate logistic regression analysis using age, gender, smoking, alcohol drinking, BMI, hemoglobin A1c, therapy for dyslipidemia, therapy for diabetes and anti-coagulation therapy as explanatory variables, odds ratios for high TAT and high PIC in the 3rd tertile group for oxidized HDL versus its 1st tertile group were significantly lower than the reference level of 1.00 (high TAT: 0.19 [0.04–0.99], p?<?0.05; high PIC: 0.33 [0.12–0.95], p?<?0.05). The frequency of high TAT or high PIC was lower in the higher tertile group for oxidized HDL than in its lower tertile group. Thus, oxidized HDL is thought to be inversely associated with both blood coagulation and fibrinolysis in patients with type 2 diabetes.     

Ferrokinetic evaluation of erythropoiesis in patients with myelodysplastic syndromes

Erythropoietic activity in patients with myelodysplastic syndrome (MDS) was evaluated by ferrokinetic measurements. Since the conventional plasma iron turnover of MDS patients increased with plasma iron levels after multiple blood transfusions, erythron transferrin uptake was chosen as a parameter of erythroid marrow activity. Although a correlation was shown between plasma iron level and plasma iron turnover (r = 0.50, 0.01 less than p less than 0.02), no correlation existed between the plasma iron level and erythron transferrin uptake (r = 0.25, p greater than 0.1). Erythron transferrin uptake, independent of plasma iron, was significantly higher in MDS patients than in normal subjects (110.6 +/- 67.6 and 67.6 +/- 18.8 mumol/l/dl, respectively; 0.01 less than p less than 0.02). An increased erythropoiesis occurring concomitantly with morphologically normal or increased erythroid cellularity was demonstrated in patients with MDS. The measurement of erythron transferrin uptake might be valuable as an accurate expression of erythroid activity in the hyperferremic state.     

Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces proximal tubular necrosis, a consequence of lipid peroxidation, that finally leads to a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation as monitored by formation of thiobarbituric acid-reactive substances and free 4-hydroxy-2-nonenal (HNE) was observed in the kidney homogenates of rats treated with Fe-NTA. Based on the fact that HNE is capable of reacting with cellular proteins, we attempted to detect the localization of HNE-modified proteins in rat kidney tissues with an immunohistochemical procedure. By means of an immunohistochemical technique using polyclonal antibody against the HNE-modified proteins, it was shown that HNE-modified proteins are formed in the target cells of this carcinogenesis model. HNE-modified proteins were detected in the renal proximal tubules 1 hr after i.p. administration of Fe-NTA (15 mg of iron per kg). Intense positivity was found in the cells with degeneration. After 6 hr, the level of HNE-protein conjugates decreased due to the subsequent necrosis. The intensity of the immunochemical reaction with HNE-modified proteins increased in parallel with an increase in the amounts of thiobartituric acid-reactive substances and free HNE that were found. Furthermore, histochemical detection of aldehydes by cold Schiff's reagent demonstrated that location of aldehydes was identical to that of the HNE-modified proteins determined by immunohistochemical procedures. It would thus appear that the production of HNE, a genotoxic and mutagenic aldehyde, and its reaction with proteins may play a role in Fe-NTA-induced renal carcinogenesis.     

Papillary fibroelastoma in the left ventricular outflow tract

Summary We report a case of a papillary fibroelastoma originating from the left ventricular endocardium in the outflow tract which was discovered by echocardiography in an asymptomatic patient. Two echocardiographic features were observed: (1) the tumor surface was smooth, and characteristic papillary formation was not detected; and (2) the outline of the mass was clearly defined as a dense echo, with the central, radiolucent, portion surrounded by a highly refractive linear echo at the level of the maximum diameter of the mass. The excised tumor was covered with a gelatinous substance that masked multiple papillae on the surface, but its echolucent center could not be explained by the pathology of the tumor which was solid centrally. Our case indicates that a papillary fibroelastoma may sometimes show echocardiographic findings similar to those of a myxoma, although other investigators have not noted the smooth surface and the echolucent center makes it indistinguishable from a myxoma. Thus, in some cases, it is difficult to distinguish papillary fibroelastoma from myxoma by echocardiography.     

Human interleukin 6 is a direct promoter of maturation of megakaryocytes in vitro

The response of cells of the murine megakaryocytic lineage to human interleukin 6 (IL-6) was assessed in serum-depleted cultures using a variety of biological assays. IL-6 alone had no influence on megakaryocytic colony formation but augmented the numbers of these colonies induced by the multipotent colony-stimulating factor interleukin 3. However, in liquid marrow cultures, IL-6 alone promoted marked increments in megakaryocytic size and the activity of acetyl-cholinesterase, a marker enzyme of the lineage. Moreover, IL-6 induced a significant shift toward higher ploidy classes when megakaryocytic DNA was quantitated by flow cytometry. To determine whether the influence of IL-6 on megakaryocytic maturation was direct, the factor was added to cultures of single megakaryocytes isolated from megakaryocytic colonies. Fifty-four percent of these cells increased in size compared with 19% of those grown without IL-6. The data show that human IL-6 is a potent direct-acting growth factor for murine megakaryocytes with activity promoting maturation of that lineage.     

Case of mixed connective tissue disease associated with autoimmune hepatitis

Summary A 56-year-old female with mixed connective tissue disease (MCTD) who developed autoimmune hepatitis is described. Hepatitis was controlled effectively by the corticosteroid therapy. Biopsy of the liver revealed swelling and hydropic degeneration of hepatocytes, accompanied by Councilman's body formation and focal necrosis. These histological findings differ from those in three previously described cases. A relationship between MCTD and liver involvement appears possible.     

Metastatic gastrinoma to the liver 20 years after primary resection

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up. Received: August 19, 1999 / Accepted: January 28, 2000     

Difference in the Burst Patterns of Digastric and Mylohyoid Activities during Feeding in the Freely Behaving Rabbit

Burst patterns in the digastric, mylohyoid, and masseter muscles and the resultant jaw movement orbits during chewing and swallowing were investigated in the freely behaving rabbit. Activities in the posterior mylohyoid fibers consisted of two continuous bursts. Peaks in the first burst of the posterior fibers occurred in the middle part of opening and preceded the digastric burst. Peaks in the second burst occurred in the final part of opening and coincided with those in the working side of the digastric burst. After removal of the bilateral digastric muscles, the gape size during chewing was largely reduced in the final part of opening and in the early part of closing. The results suggest that (a) the digastric may have a role in opening the mandible widely beyond the rest position but may not have a major role in the control of the horizontal (mediolateral) jaw movement, (b) the posterior mylohyoid fibers may have a function as an elevator of the tongue in the early part of opening, and (c) the posterior mylohyoid fibers may have a function as a depressor of the jaw in the late part of opening. Electromyographic burst in the mylohyoid muscle began with marked activity in the mid-closing phase. The results support a role for the mylohyoid muscle as a leading muscle of swallowing. Swallowing events in the rabbit are easily distinguished from the activities of the mylohyoid muscle and the thyrohyoid muscle.