Combined operation for renovascular hypertension and ischemic heart disease

We have experienced two patients of ischemic heart disease associated with renovascular hypertension. Patient 1 (60-year-old man) underwent LV aneurysmectomy and triple aortocoronary bypass grafting (saphenous vein to diagonal branch, left internal mammary artery to obtuse marginal branch, and right gastroepiploic artery to right coronary artery). Seventy five days after the initial cardiac surgery endarterectomy for the left renal artery and bifurcated Dacron graft implantation for the iliac artery obstruction were performed. Patient 2 (62-year-old woman) underwent simultaneous operation of both right nephrectomy and triple aortocoronary bypass grafting (saphenous vein grafts to obtuse marginal branch and right coronary artery, and left internal mammary artery to left anterior descending artery). Their postoperative courses were uneventful except unstable and high blood pressure for four to seven days after the operation. It appears that it should be decided to achieve either simultaneous or two stage approach for ischemic heart disease associated with renovascular hypertension based on the preoperative cardiac function. And both postoperative cardiac function and hypertension should be carefully managed until the blood pressure becomes stable after the surgery.     

Effects of fasting on biperiden pharmacokinetics in the rat

The effects of fasting on the pharmacokinetics of biperiden in rats were examined. Total clearance of biperiden was greater than 90% ascribable to hepatic clearance and was essentially blood-flow dependent. The number of compartments in the preferred pharmacokinetic model of biperiden changed from three (for normal rats) to two (for fasted rats). The smaller mean residence time (MRT) values found for fasted rats were attributable to decreases in distribution volume. Biperiden showed much higher lipophilicity than haloperidol, thiopental, and hexobarbital, and its tissue-to-plasma partition coefficient in adipose tissue was 20-fold higher than that in muscle. The influence of changes in volumes of adipose tissue and muscle on distribution volume (Vdss/BW) was evaluated from tissue-to-plasma partition coefficients. The value of Vdss/BW was predicted to decrease with decrease of adipose tissue, and to increase with decrease of muscle tissue. These results suggest that the observed decrease of Vdss/BW in fasted rats reflects reduced capacity to trap biperiden in the body, especially in adipose tissue. Possible clinical implications of these results are discussed.     

Polyglucosan bodies in the central nervous system of a fox.

Polyglucosan bodies (PGB) in the central nervous system of an old male fox, Vulpes vulpes japonica, without neurological signs were examined by light and electron microscopy, lectin histochemistry and immunohistochemistry. Fox PGB were round, slightly-basophilic and PAS-positive structures. Most of the bodies were situated free in the neuropil. Electron microscopically, fox PGB were composed mainly of branching filaments and electron-dense material. Lectin histochemistry revealed that fox PGB contained mannose and galactose in addition to glucose. Fox PGB were immunoreactive for monoclonal antibodies raised against human polyglucosan. These findings indicate that fox PGB are similar to feline ones.     

A differentiation-inducing factor produced by the osteoblastic cell line MC3T3-E1 stimulates bone resorption by promoting osteoclast formation

We have reported that the differentiation-inducing factor (DIF) is present in conditioned medium of mouse osteoblast-like cell (MC3T3-E1) cultures. In the present study, the DIF from conditioned medium of MC3T3-E1 cells was partially purified and its biologic activity was examined. The DIF was purified by monitoring the induction of phagocytic activity of mouse myeloblastic leukemia cells (M1). The DIF induced differentiation of not only M1 cells but also mouse myelomonocytic cells (WEHI-3). Furthermore, the DIF increased the in vitro bone-resorbing activity and the osteoclast number in mouse calvaria. The increases were inhibited by the addition of either salmon calcitonin or indomethacin. When mouse bone marrow cells were cultured with the DIF for 8 days, formation of osteoclast-like multinucleated cells was stimulated dose dependently. The DIF from MC3T3-E1 cells appeared to be different from interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor beta (TGF-beta). These results suggest that the DIF partially purified from osteoblast-like cell cultures stimulates osteoclastic bone resorption by promoting differentiation and fusion of osteoclast progenitors to form multinucleated osteoclasts.     

Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia

We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line-derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells.     

Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839)

Gefitinib (Iressa, ZD1839), an inhibitor of epidermal growth factor receptor-tyrosine kinase, has shown potent anti-tumor effects and improved symptoms and quality-of-life of a subset of patients with advanced non-small cell lung cancer (NSCLC). However, a large portion of the patients showed no effect to this agent. To establish a method to predict the response of NSCLC patients to gefitinib, we used a genome-wide cDNA microarray to analyze 33 biopsy samples of advanced NSCLC from patients who had been treated with an identical protocol of second to seventh line gefitinib monotherapy. We identified 51 genes whose expression differed significantly between seven responders and 10 non-responders to the drug. We selected the 12 genes that showed the most significant differences to establish a numerical scoring system (GRS, gefitinib response score), for predicting response to gefitinib treatment. The GRS system clearly separated the two groups without any overlap, and accurately predicted responses to the drug in 16 additional NSCLC cases. The system was further validated by the semi-quantitative RT-PCR, immunohistochemistry and ELISA for serological test. Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein that was significantly over-expressed in non-responders but undetectable in responders, leads to resistance of NSCLC cells to gefitinib in vitro. Our results suggested that sensitivity of a given NSCLC to gefitinib can be predicted according to expression levels of a defined set of genes that may biologically affect drug sensitivity and survival of lung cancer cells. Our scoring system might eventually lead to achievement of personalized therapy for NSCLC patients.     

CDw108 expression during T-cell development

We recently reported a gene encoding the human CDw108, a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is preferentially expressed on activated T lymphocytes and erythrocytes. The present study investigated the expression of CDw108 on various tissues and cells, particularly on T cells during development. The murine CDw108 cDNA was cloned initially, and it was highly homologous to the human CDw108 (88.0% or 89.3% similarity at the nucleotide or amino acid level, respectively) or identical to the murine semaphorin K1/Sema7A. The CDw108 mRNA was demonstrated in a few tissues including thymus and brain with the highest expression coming on day 7 in whole embryo followed by relatively consistent expression during development. Cell-surface expression of the CDw108 during T-cell development was further examined by flow cytometry in the human umbilical cord blood and thymus. It was preferentially expressed on a CD34+ stem cell population of umbilical cord blood, and CD3dull CD34+/- CD117 (c-kit)+ CD4bright CDbright cells in the thymus that are involved in the stage of positive selection. These results suggest the contribution of CDw108 in T-cell development, especially in the stage of positive selection in the thymus.     

Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer

Background. Exact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities, including surgery, chemotherapy, and radiotherapy.

Methods. The accuracy of preoperative tumor staging by using an esophagography, esophagoscopy, percutaneous and endoscopic ultrasonography, and computed tomography was assessed in 224 patients with resectable esophageal cancer. The results of tumor staging by these tests were compared prospectively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification.

Results. For the T category, the overall accuracy was 80%. For the N category, overall accuracy was 72%, with a sensitivity of 78%, a specificity of 60%, and a positive predictive value of 78%. Overall, the accuracy of stage grouping was 56%.

Conclusions. Either the T or N categories can be predicted reliably by clinical staging techniques. However, the preoperative stage grouping might not be valid in resectable, localized esophageal cancer.     

Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.