Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro.

Leptin, the product of ob gene, is an endocrine hormone that regulates adipose tissue mass. Recently, leptin has been found to generate a growth signal involving a tyrosine kinase-dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor (Ob-R) in endothelial cells. However, it is not clear how leptin functions to promote multi-step processes involved in the neovascularization at the atherosclerotic plaque. We have examined the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical analysis of human atherosclerotic aorta revealed an increased expression of Ob-R in the intima of neorevascularized regions and of both MMPs and TIMPs predominantly in the endothelial lining of intimal neovessels and macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a comparable sensitivity of angiogenic activity to those of vascular endothelial growth factor (VEGF). The immunohistological analysis of the leptin-treated rat cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with pluralistic properties including a mitogenic activity on vascular endothelial cells, plays a role in matrix remodeling by regulating the expression of MMPs and TIMPs. Taken together, our findings further provide evidences for leptin's role as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant vasculature under duress like atherosclerosis.

Expression of osteopontin in calcified coronary atherosclerotic plaques.

Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.

Apoptosis in dilated cardiomyopathy.

OBJECTIVE: Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS: Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS: Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4%, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION: The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.

Prospective comparison of laparoscopic and traditional colposuspensions in the treatment of genuine stress incontinence.

OBJECTIVE: To compare prospectively the results of laparoscopic and traditional colposuspensions in the treatment of genuine stress incontinence and to evaluate the efficacy, technique, and functional and anatomical changes after these two procedures. MATERIALS AND METHODS: Ninety-two patients with urodynamically proven genuine stress incontinence participated in this study, with 46 patients randomly allocated to laparoscopic colposuspension, and the other 46 patients to the traditional procedures. All patients had repeat studies at least 3 months after operation. RESULTS: The bladder neck position was significantly elevated after operation either at rest or during straining in both groups (all p < 0.001), but it was higher in the traditional group than the laparoscopy group during straining (p < 0.05). Comparison of urodynamics before and after operation in both groups showed significantly increased minimal urethral resistance and improved pressure transmission ratios at the proximal urethra (Q2). The blood loss was less in the laparoscopy group. The duration of bladder drainage after laparoscopic colposuspension was shorter, and was not affected by subsequent laparotomy. The operative time was almost the same. The success rate of the laparoscopy group was lower than that of the traditional group (80.4% vs. 95.6%, p = 0.044). The complication rates were 10.8% and 17.4% respectively. CONCLUSION: Laparoscopic colposuspension is an effective method for the treatment of GSI, as documented by anatomical and functional assessments. However, the success rate is still lower than for the traditional procedure.

Sonographic and clinical findings of granulosa cell tumor.

BACKGROUND: Granulosa cell tumor (GCT) accounts for roughly 1.5% of all ovarian neoplasms and 5-10% of ovarian cancers. GCT, which may have profound end-organ effects, has attracted a significant amount of attention despite its rarity. This tumor is rare, and difficult to diagnose before operation. Until now, no specific sonographic findings have been reported. METHODS: Twelve cases of pathologically proven GCTs were diagnosed from June 1985 to March 1993. Nine of those cases had preoperative sonographic pictures taken. RESULTS: Eight out of the nine cases tested exhibited a complex multicystic sonographic pattern. For a case evaluated by a transvaginal color and pulsed Doppler assessment, the blood vessels located in the central part with diffuse dispersed vascular arrangement were found to have a resistance index of 0.38 and a pulsatility index of 0.50. The most common complaints of our patients were postmenopausal bleeding and lower abdominal pain. CONCLUSIONS: We conclude that complex multicystic sonographic features observed by high-resolution ultrasonography, in conjuction with a high preoperative estradiol level and clinical symptoms, may help to establish a preoperative diagnosis of GCT.

Laparoscopic para-aortic lymph node sampling in the staging of invasive cervical carcinoma: including a comparative study of 21 laparotomy cases.

OBJECTIVES: To assess the efficacy and risks of laparoscopic para-aortic lymph node sampling compared with standard laparotomy in staging cervical carcinoma. METHODS: From August 1993 through July 1994, 38 patients with biopsy-proven invasive cervical carcinoma (24 early and 14 advanced invasive cancers) were entered into the study. This was a prospective study of laparoscopic para-aortic lymphadenectomy in invasive cervical carcinoma, with patients serving as their own controls. Video laparoscopic lymph node sampling was performed. In patients with early invasive cancer, the nodes were sent for frozen section and, if negative, laparotomy was performed to look for any residual nodes. Radical hysterectomy was performed immediately if residual nodes were negative. Patients with either nodal metastasis on frozen section or with advanced cancer underwent para-aortic lymphadenectomy only. The operative technique was also evaluated. RESULTS: Laparoscopy required an average of 77 min (S.D. 40), with an average blood loss of 116 ml (S.D. 321). The average number of nodes was 15 (S.D. 7). At subsequent laparotomy the average number of residual nodes found was 0.4 (S.D. 0.9) and none showed metastasis. One vena cava laceration and one ureteral injury required immediate repair, and two patients were too obese to undergo laparoscopy. CONCLUSIONS: Laparoscopic para-aortic lymph node sampling is a less invasive, reliable method for staging invasive cervical carcinoma and can substitute for traditional open procedures. The incidence of risks with this method appears to be low.

Acute myocardial infarction in the young adults.

A review was done on 631 patients with acute myocardial infarction who underwent coronary angiography within 30 days after onset of myocardial infarction at Yonsei University Severance Hospital from January, 1985, to August, 1993. The incidence of acute myocardial infarction in patients under 40 years of age was 10.3% (65/631). Acute myocardial infarction below the fourth decades was the predominant disease of men. Risk factor analysis revealed a history of cigarette smoking and hypercholesterolemia were more frequently found in the young patients, but a history of hypertension and diabetes were more frequently found in the elderly patients. Angiographically, the incidence of one vessel disease and normal or minimal lesion coronary anatomy were more frequent in the young patients and incidence of multi-vessel disease were more frequent in the elderly patients. Of the 65 patients under 40 with acute myocardial infarction, the patients with multi-vessel disease tended to have a history of diabetes mellitus in comparison with those with normal coronary anatomy or one vessel disease.