An Electrophysiological Experimental Study on the Spontaneous Sympathetic Nerve Activity in the Rostral Ventrolateral Medulla Oblongata

The sympathetic postganglionic nerve fibers, which are controlled by preganglionic fibers originating from  specific nuclei in the medulla oblongata, and the thoracic and upper lumbar segments of the spinal cord,  together with the local autoregulatory mechanisms and circulating hormones, directly influence the cardiovascular  function. Recently, the studies on the sympathetic preganglionic fibers have remarkably progressed,  and the anatomical (Strack et al., 1988), functional (Janig, 1985), and chemical (Krukoff, 1985)  characteristics of the synaptic input have been clarified. However, the peripheral sympathetic nerve activities  vary depending on the organs concerned (including the skin, muscle, or internal organs) as they have  their own physiological characteristics (Janig and McLachlan, 1986) including the response pattern to the  peripheral receptor stimulation. Many areas, including the histological and functional roles of the peripheral  part, nerve centers, and central pathway of the circulatory system, are still unknown. The peripheral sympathetic nerve activities in humans consist of the skin sympathetic activity (SSA) that  controls the sweat glands / skin vasomotion, and the muscle sympathetic activity (MSA) that controls the  vascular smooth muscles in the skeletal muscles, and each activity has different characteristics. SSA  involving regulation of the body temperature and MSA involving regulation of the blood pressure can be  separately recorded (Burke et al., 1977; Hagbarth et al., 1975; Vallbo et al., 1979; Wallin and Eckberg,  1982; Yatomi et al., 1989) from the sympathetic postganglionic efferent fibers by microneurography  (Hagbarth et al., 1972). By recording and comparing the action patterns and responses to stimulations of the premotor nuclei, along  with other vital rhythms, we hoped to clarify the complex mechanism of the sympathetic nerve activities  and to contribute in the treatment of disorders resulting from sympathetic dysfunction. We also report our  findings on the premotor nuclei that produce sympathetic preganglionic fiber activities by using topographic  mapping analysis of the changes in the central action potentials in the rostral ventrolateral medulla  oblongata (RVLM) region to visually capture the complicated action patterns to compare the cross correlations  with MSA and SSA using microneurography and ECG.

Diffuse Endobronchial Wall Spread of Metastatic Breast Cancer

We present here a case of diffuse tracheobronchial wall spread of metastatic breast cancer who was successfully treated with trastuzumab plus vinorelbine chemotherapy. The patient had a left radical mastectomy for breast cancer in March 2000 and developed persistent cough and dyspnea in November 2006. Pulmonary function test demonstrated an obstructive pattern. Chest computed tomography showed a wall thickening of trachea and right side bronchus, but radiographic findings including 18F-fluorodeoxyglucose positron emission tomography failed to detect the locations of disease in the lung. The findings on bronchofiberscopy showed edematous tracheobronchial mucosa, but also failed to visually detect direct masses. Transbronchial biopsy specimens revealed involvement of metastatic breast cancer. The patient was treated with trastuzumab plus vinorelbine chemotherapy and the wall thickening of bronchial tree and clinical symptoms were improved. Although endobronchial metastasis in metastatic breast cancer is not uncommon, diffuse spread without forming intraluminal mass is extremely rare. The pattern of endobronchial metastasis should be considered in patients with malignancies even when radiographic abnormalities are undetectable

Phase II Trial of Biweekly Paclitaxel and Gemcitabine as Second-Line Chemotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy

A phase II study was conducted to evaluate the feasibility and efficacy of biweekly administration of paclitaxel and gemcitabine in patients with non-small cell lung cancer (NSCLC) who had been treated previously with platinum-based chemotherapy. Paclitaxel (150 mg/m2) and gemcitabine (1,000 mg/m2) were administered biweekly for at least 4 cycles. Thirty-one patients with a median age of 64 years (39-75 years) were enrolled in this study(stage IIIB/IV :11/20,PS 0/1/2:13/16/2).Partial response was observed in 7 cases (23%), and stable disease was seen in 18 cases (58%).Median survival time was 8.8 months with a one-year survival rate of 41.9 %.Hematological toxicities were mild and neutropenia of grade 3 or above was observed in one patient (3%). Non-hematological toxicities were also mild, including neurotoxicity (3%). Biweekly paclitaxel and gemcitabine combination chemotherapy was effective and tolerated well as second-line therapy against NSCLC.Article信州医学雑誌 59(6): 411-418(2011)departmental bulletin pape

Effects of bronchodilators on dynamic hyperinflation following hyperventilation in patients with COPD

‘The definitive version is available at www.blackwell-synergy.com '.ArticleRespirology. 12(1): 93-99 (2007)journal articl

Comparison of Distance of 6-min Walk Test and the Incremental Shuttle Walk Test with Lung Function or Quality of Life in Patients with Chronic Obstructive Pulmonary Disease

Article信州医学雑誌 61(2):57-64(2013)journal articl

Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression

Glycosylphosphatidylinositol (GPI)-anchored proteins play crucial roles in various enzyme activities, cell signaling and adhesion, and immune responses. While the molecular mechanism underlying GPI-anchored protein biosynthesis has been well studied, the role of zinc transport in this process has not yet been elucidated. Zn transporter (ZNT) proteins mobilize cytosolic zinc to the extracellular space and to intracellular compartments. Here, we report that the early secretory pathway ZNTs [ZNT5-ZNT6 heterodimers (ZNT5-6) and ZNT7-ZNT7 homodimers (ZNT7)], which supply zinc to the lumen of the early secretory pathway compartments are essential for GPI-anchored protein expression on the cell surface. We show, using overexpression and gene disruption/re-expression strategies in cultured human cells, that loss of ZNT5-6 and ZNT7 zinc transport functions results in significant reduction in GPI-anchored protein levels similar to that in mutant cells lacking phosphatidylinositol glycan anchor biosynthesis (PIG) genes. Furthermore, medaka fish with disrupted Znt5 and Znt7 genes show touch-insensitive phenotypes similar to zebrafish Pig mutants. These findings provide a previously unappreciated insight into the regulation of GPI-anchored protein expression and protein quality control in the early secretory pathway

An Assessment by In Situ Hybridization Method for Pathogens of Severe Respiratory Infection

It has been shown that the in situ hybridization (ISH)method for the detection of phagocyted bacteria in polymorphonuclear neutrophils is more sensitive than conventional blood culture in patients with sepsis.The present study was designed to further evaluate the clinical utility of the ISH method, using a commercially available kit (Hybrizep(R)), for detecting pathogens in patients with severe respiratory infections. Peripheral blood was taken from patients with severe respiratory infections for both routine blood culture and the ISH method,respectively.In addition,focal samples including sputum,bronchoalveolar lavage,central and thoracic catheter, etc. were simultaneously examined for bacterial culture. A total number of 22 specimens was examined.The positive cases by ISH were 50.0% in the respiratory infections,which were significantly higher than those in blood cultures (9.1%).However, identical pathogens in the ISH method were not isolated from blood and/or other sources in respiratory sites. These findings suggest a possibility of high frequency of bacteremia or multifactorious pathogens in severe respiratory infections.The ISH method may provide additional information on serious respiratory infections for the detection of bacteremia. However, the clinical utility by the ISH method for patients with severe respiratory infection remains undetermined. Shinshu Med J 59 : 223―228, 2011Article信州医学雑誌 59(4): 223-228(2011)departmental bulletin pape

The association of Toll-like receptor 4 gene polymorphisms with the development of emphysema in Japanese subjects: a case control study

<p>Abstract</p> <p>Background</p> <p>The principal role of Toll-like receptor 4 (TLR4) is the induction of immune responses to lipopolysaccharides. Previously, mice deficient in the <it>TLR4 </it>gene exhibited up-regulation of the NADPH oxidase system in the lungs. This resulted in increased oxidant generation and elastolytic activity, which led to pulmonary emphysema. It was suggested that TLR4 might maintain constitutive lung integrity by modulating oxidant generation. We investigated whether single nucleotide polymorphisms (SNPs) in the <it>TLR4 </it>gene were associated with the emphysema phenotype in Japanese subjects with chronic obstructive pulmonary disease (COPD).</p> <p>Results</p> <p>Seven SNPs in the <it>TLR4 </it>gene (<it>rs10759930</it>, <it>rs1927914</it>, <it>rs12377632</it>, <it>rs2149356, rs11536889</it>, <it>rs7037117</it>, and <it>rs7045953</it>) were genotyped with allelic discrimination assays. The frequencies of SNPs were compared between 106 patients with the emphysema phenotype of COPD and 137 healthy smokers. We found that the positivity of the individuals with the major G allele of <it>rs11536889 </it>was significantly less in the emphysema group than the control group (<it>p </it>= 0.019). The frequencies of the minor C allele and the distribution of the CC genotype as well as the frequency of the major haplotype that carried the minor C allele of <it>rs11536889 </it>were all significantly higher in the emphysema group than the control group (<it>p </it>= 0.0083, 0.019, and 0.004, respectively). Furthermore, the strength of the association of the CC genotype with the emphysema phenotype was in an odds ratio of 2.60 with 95% confidence intervals from 1.17 to 5.78. However, these significances were not apparent after adjust for age and smoking history by logistic regression. No associations were observed between the <it>rs11536889 </it>and the low attenuation area score, the forced expiratory volume, and the carbon monoxide diffusion capacity in the emphysema group.</p> <p>Conclusions</p> <p>The minor C allele of the <it>rs11536889 </it>SNP in the <it>TLR4 </it>gene is likely associated with the risk of developing emphysema in the Japanese population.</p