Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy

Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood blow and increased collagen synthesis. Therefore, a therapeutic approach to alter the blood flow or fibrosis directly by means of growth factors may open a new therapeutic concept in dilated cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with antifibrosis and angiogenesis effects. Using the hereditary cardiomyopathic Syrian hamster as a model of genetically determined cardiomyopathy and heart failure, the effects of overexpression of HGF on fibrosis and microvascular dysfunction were examined. HGF gene or control vector was injected by the Hemagglutinating Virus of Japan-liposome method into the anterior heart of cardiomyopathic hamsters (Bio 14.6) under echocardiography once a week, from 12 to 20 weeks of age (total, 8 times). Blood flow, as assessed by a laser Doppler imager score, and the capillary density in hearts, as assessed by alkaline phosphatase staining, were significantly increased in hamsters transfected with HGF gene compared with control-vector-transfected hamsters (P<0.01). In contrast, the fibrotic area was significantly decreased in hamsters transfected with HGF gene compared with control (P<0.01). Overall, in vivo experiments demonstrated that transfection of HGF gene into the myocardium of cardiomyopathic hamsters stimulated blood flow through the induction of angiogenesis and reduction of fibrosis. These results suggest that HGF gene transfer may be useful to protect against myocardial injury in cardiomyopathy through its cardioprotective effects such as antifibrosis and angiogenesis actions.     

Efficacy of continuous hemodiafiltration for patients with congestive heart failure

BACKGROUND/AIMS: The basic principle of treatment of congestive heart failure is achieving adequate control of preload and afterload through enhancement of cardiac contractility. In severe cases, however, we have usually applied continuous hemodiafiltration (CHDF) as a type of mechanical support. In this study, we investigated hemodynamic changes caused by CHDF in patients with congestive heart failure. METHODS: We treated seven patients with congestive heart failure complicated by multiple organ failure by CHDF over 72 h, during which we measured hemodynamic parameters to determine their changes. RESULTS: Implementation of CHDF resulted in a significant decrease in pulmonary artery occluded pressure and significant increases in cardiac index and left ventricular stroke work index. In addition, 72-hour cumulative water balance was found to be -1,791 +/- 2,119 ml, and systemic vascular resistance index decreased significantly. CONCLUSION: Hemodynamics of patients were improved with CHDF through strict control of preload and consequently tissue oxygen metabolism was improved.     

Use of a new venous cannula for minimally invasive cardiac surgery

Interest in minimally invasive cardiac surgery (MICS) for cardiac disease continues to increase, because it causes less surgical trauma and produces a better cosmetic appearance. We introduced the transxiphoid approach without sternotomy for correction of congenital heart defects. To improve exposure of the cardiac lesion during MICS, we developed a new venous cannula that is made of wire reinforced silicone, with an inflatable balloon attached at the tip. The advantages of this cannula are its extreme flexibility and that a tape does not need to be placed around the vena cava. During a period of 12 months, eight children underwent closure of atrial septal defects. The approach consisted of a 4 to 5 cm low midline incision with division of the xiphoid only. The new venous cannula was used as the superior vena cava cannula, all the patients survived the operation. This new venous cannula provided better exposure during cardiac surgery through a limited incision and is beneficial for minimally invasive cardiac surgery.     

Nitric oxide inhalation is useful in the management of right ventricular failure caused by myocardial infarction

OBJECTIVE: To describe hemodynamic improvement in a patient treated with nitric oxide (NO) inhalation in the management of right ventricular failure caused by myocardial infarction. DESIGN: Case report. SETTING: An intensive care unit of a university hospital. PATIENT: A 66-yr-old man with severe right ventricular failure caused by acute myocardial infarction. INTERVENTIONS: Nitric oxide inhalation through a ventilator circuit. MEASUREMENTS AND MAIN RESULTS: The patient complained of chest pain. When myocardial infarction was diagnosed, he underwent percutaneous transluminal coronary angioplasty and percutaneous transluminal coronary recanalization, but they were not effective. We instituted intra-aortic balloon pumping and brought the patient to the intensive care unit (ICU). Even with high-dose inotropic support, his hemodynamics deteriorated gradually. On the patient's seventh day in the ICU, we started NO inhalation at 5-10 ppm in an attempt to relieve his right heart failure. Immediately after NO inhalation was started, his hemodynamics improved significantly, and we could wean the patient from intra-aortic balloon pumping. NO inhalation was continued for 9 days and was successfully discontinued without circulatory deterioration. He was discharged from our hospital uneventfully. CONCLUSION: Nitric oxide inhalation improved hemodynamics in our patient with right ventricular failure after myocardial infarction. Our report suggests that a clinical trial of NO treatment for severe right ventricular failure caused by myocardial infarction is warranted.     

Feline host range of canine parvovirus: recent emergence of new antigenic types in cats

Since the emergence of Canine parvovirus (CPV-2) in the late 1970s, CPV-2 has evolved consecutively new antigenic types, CPV-2a and 2b. Although CPV-2 did not have a feline host range, CPV-2a and 2b appear to have gained the ability to replicate in cats. Recent investigations demonstrate the prevalence of CPV-2a and 2b infection in a wide range of cat populations. We illustrate the pathogenic potential of CPV in cats and assess the risk caused by CPV variants.     

A case of esophageal squamous cell carcinoma metastatic to the breast

Metastasis to the breast from extramammary malignancies is rare. There are especially few reports of metastasis from esophageal cancer. We report the pathological and autopsy findings of a 44-year-old man with advanced esophageal cancer and a left breast tumor. Squamous cell carcinoma invading the mammary glands was demonstrated histologically. Immunostains for ER, PgR, and ErbB-2 were negative. At autopsy, metastatic lesions were found in lung, liver, diaphragm, peritoneum, spine, and mediastinal lymph nodes, with no evidence of metastasis to the skin. While metastatic breast tumors are rarely the initial sign of malignancy, it is important to distinguish a metastasis from primary breast cancer to avoid unnecessary conflicting treatments.     

Enhancement of Cisplatin Sensitivity in High Mobility Group 2 cDNA-transfected Human Lung Cancer Cells

To elucidate the role of high mobility group 2 protein (HMG2) in cis -diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a human HMG2 -transfected human non-small cell lung cancer cell line, PC-14/HMG2. The HMG2 mRNA expression level was approximately twice those of parental PC-14 and mock-transfected PC-14/CMV. Gel mobility shift assay revealed a CDDP-treated DNA-protein complex in the nuclear extract of PC-14/HMG2, which was not found in the extracts of PC-14 and PC-14/CMV. This complex formation was subject to competition by CDDP-treated non-specific salmon sperm DNA, indicating that ectopic HMG2 recognizes CDDP-damaged DNA. PC-14/HMG2 showed more than 3-fold higher sensitivity to CDDP than PC-14 and PC-14/CMV. The intracellular platinum content of PC-14/HMG2 after exposure to 300 μM CDDP was 1.1 and 1.5 times that of PC-14 and PC-14/CMV, respectively. Cellular glutathione levels were not different in these cell lines. Repair of DNA interstrand cross-links determined by alkaline elution assay was decreased in PC-14/HMG2. These results suggest that HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA lesion induced by CDDP.     

Production of inhibin A and inhibin B in human ovarian sex cord stromal tumors

OBJECTIVE: Our purpose was to examine the cellular localization of inhibin subunits and messenger ribonucleic acid expressions for the inhibin subunits and the serum levels of inhibin A and inhibin B in human ovarian sex cord stromal tumors. STUDY DESIGN: We examined the immunohistochemical localization of the inhibin subunits and the expression of the corresponding messenger ribonucleic acids by Northern blot analysis in a granulosa cell tumor and a Sertoli-Leydig cell tumor. We also measured serum concentrations of dimeric inhibin A and inhibin B by two-site enzyme-linked immunosorbent assay. RESULTS: Immunostaining specific for the inhibin α, βA, and βB subunits was observed in the granulosa cell tumor. In the Sertoli-Leydig cell tumor we observed immunostaining specific for the α subunit in Leydig tumor cells and that specific for the βA subunit in Sertoli tumor cells and that specific for the βB subunit in both tumor cells. Northern blot analysis revealed the presence of messenger ribonucleic acids for the α, βA, and βB subunits in the granulosa cell tumor and the Sertoli-Leydig cell tumor. The serum levels of dimeric inhibin A and inhibin B in patients were elevated preoperatively and decreased progressively after surgery. CONCLUSION: Our results suggest that inhibin A and inhibin B are produced by the human sex cord stromal tumors and that inhibins might be the useful markers of the tumors.(Am J Obstet Gynecol 1997;177:7)     

Effect of Glutathione Depletion on Cisplatin Resistance in Cancer Cells Transfected with the γ-Glutamylcysteine Synthetase Gene

Overexpression of the human γ-glutamylcysteine synthetase (γ-GCS) gene resulted in cisplatin resistance with an increased glutathione (GSH) content, increased ATP-dependent glutatbione S-conjugate export pump (GS-X pump) activity and decreased platinum accumulation in human lung cancer cells transfected with a γ-GCS cDNA expression vector, as we previously reported. In this study, we examined the effects of buthionine sulfoximine (BSO), a specific inhibitor of γ-GCS, to determine whether GSH depletion alters cisplatin resistance in a γ-GCS-transfected cell line, SBC-3/ GCS. In the presence of 10 μM BSO for 4 days, SBC-3/GCS still showed resistance to cisplatin, although it was partially reversed. Under these conditions, GS-X pump activity remained up-regulated in spite of low GSH content, and the platinum content was decreased. These data suggest that the GS-X pump itself influences cisplatin resistance, as well as cellular GSH content.     

Interferon-γ-inducing Factor Gene Transfection into Lewis Lung Carcinoma Cells Reduces Tumorigenicity in vivo

To investigate the immunoregulatory effect of murine mterferon-γ-inducing factor (mIGIF), we transfected Lewis lung carcinoma (IXC) cells with a mammalian expression vector containing the mIGIF complementary DNA. The culture medium of the transfectant cells stimulated interferon-γ (IFN-γ) production by spleen cells in vitro in the presence of anti-CD3 antibody and markedly potentiated the effect of interleukin-12 (IL-12) on IFN-γ production by spleen cells. mIGIF transfectant cells showed reduction of tumorigenicity and induction of an in vivo immimo-protective effect against the parental LLC cells. To examine the combined effect of systemic administration of recomhinant IL-12 (rIL-12) and local mIGIF on the tumorigenicity, mice were challenged with LLC or transfectant cells on day 0, and the tumor-bearing mice were injected with 50 ng of rIL-12 intraperitoneally from day 7 to 11. Systemic rIL-12 showed an anti-tumor effect. However, mIGIF gene expression did not potentiate this effect of systemic rIL-12 in vivo.