Prophylactic effect of rikkunshito, an herbal medicine, for chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin-based chemotherapy.

Rikkunshito has been shown to improve upper gastrointestinal symptoms and anorexia. The aim of this study was to evaluate whether rikkunshito improves chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin (CBDCA)-based chemotherapy. A retrospective before-and-after comparison study was conducted in patients with thoracic cancer receiving the first cycle of CBDCA-based chemotherapy. Among 61 eligible patients, 34 received standard antiemetic therapy with a combination of 5-hydroxytryptamine-3 receptor antagonist and dexamethasone from September 2012 and June 2013 (standard group), while the other 27 received the standard antiemetic therapy plus oral rikkunshito from July 2013 and December 2014 (rikkunshito group). The rates of no nausea showed no significant difference between the standard and rikkunshito group (Overall phase: 64.7 % for standard group vs 74.1 % for rikkunshito group, p = 0.579). Subgroup analysis indicated that, in female patients, the rates of no nausea in rikkunshito groups was significantly higher than in standard group (overall phase: 44.4 % vs 100 %, p = 0.034). Rikkunshito did not demonstrate an additional prophylactic effect on standard antiemetic therapy for nausea in patients with thoracic cancer receiving CBDCA-based chemotherapy, but showed a prophylactic effect of nausea in female patients.

Muscle stiffness of posterior lower leg in runners with a history of medial tibial stress syndrome.

Previous history of medial tibial stress syndrome (MTSS) is a risk factor for MTSS relapse, which suggests that there might be some physical factors that are related to MTSS development in runners with a history of MTSS. The relationship between MTSS and muscle stiffness can be assessed in a cross-sectional study that measures muscle stiffness in subjects with a history of MTSS, who do not have pain at the time of measurement, and in those without a history of MTSS. The purpose of this study was to compare the shear elastic modulus, which is an index of muscle stiffness, of all posterior lower leg muscles of subjects with a history of MTSS and those with no history and investigate which muscles could be related to MTSS. Twenty-four male collegiate runners (age, 20.0±1.7 years; height, 172.7±4.8 cm; weight, 57.3±3.7 kg) participated in this study; 14 had a history of MTSS, and 10 did not. The shear elastic moduli of the lateral gastrocnemius, medial gastrocnemius, soleus, peroneus longus, peroneus brevis, flexor hallucis longus, flexor digitorum longus, and tibialis posterior were measured using shear wave elastography. The shear elastic moduli of the flexor digitorum longus and tibialis posterior were significantly higher in subjects with a history of MTSS than in those with no history. However, there was no significant difference in the shear elastic moduli of other muscles. The results of this study suggest that flexor digitorum longus and tibialis posterior stiffness could be related to MTSS.

Disruption of human stratum corneum lipid structure by sodium dodecyl sulphate.

OBJECTIVE: Surfactants are major ingredients of body soaps and cleansers, and such harsh ones have been demonstrated to damage the skin. Stratum corneum (SC), the outermost barrier of the skin layer, is rich in intercellular lipids. This lipid structure can be disrupted by surfactants, impairing the barrier function of the skin. Thus, we investigated the surfactant-induced disruption of the intercellular lipid structure of human SC at the molecular level using synchrotron X-ray diffraction. METHODS: SC samples from the breast of female Caucasians were treated with sodium dodecyl sulphate (SDS) and analysed by small-angle and wide-angle X-ray diffraction. RESULTS: We found that an aqueous SDS solution affected the long lamellar structure, which became disorganized. The final disordered lipid state was reached through two or more types of structural change. We propose that the disordered lipid state results from incorporation of SDS into the long lamellar structure. In contrast, the lattice constants in the short lamellar and the hydrocarbon-chain packing structures remained almost unchanged after SDS treatment. CONCLUSION: We conclude that the disruption of the long lamellar structure plays a key role in the damage to the SC caused by detergents. To our knowledge, this is the first report to clarify the details of the disorganization of the intercellular lipid structure upon surfactant application. The knowledge obtained herein may allow the development of skin restoration methods and cleanser products that do not affect skin barrier functions.

Unilateral ablation of trunk superficial neuromasts increases directional instability during steady swimming in the yellowtail kingfish Seriola lalandi.

Detailed swimming kinematics of the yellowtail kingfish Seriola lalandi were investigated after unilateral ablation of superficial neuromasts (SNs). Most kinematic variables, such as tail-beat frequency, stride length, caudal fin-beat amplitude and propulsive wavelength, were unaffected but lateral amplitude at the tip of the snout (A0 ) was significantly increased in SN-disrupted fish compared with sham-operated controls. In addition, the orientation of caudal fin-tip relative to the overall swimming direction of SN-disrupted fish was significantly deflected (two-fold) in comparison with sham-operated control fish. In some fish, SN disruption also led to a phase distortion of the propulsive body-wave. These changes would be expected to increase both hydrodynamic drag and thrust production which is consistent with the finding that SN-disrupted fish had to generate significantly greater thrust power when swimming at ≥1·3 fork lengths (LF ) s(-1) . In particular, hydrodynamic drag would increase as a result of any increase in rotational (yaw) perturbation and sideways slip resulting from the sensory disturbance. In conclusion, unilateral SN ablation produced directional instability of steady swimming and altered propulsive movements, suggesting a role for sensory feedback in correcting yaw and slip disturbances to maintain efficient locomotion.

Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice.

BACKGROUND: Orchestration of two major classes of angiogenic factors-namely, vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2)-has been shown to play a pivotal role in tumour angiogenesis, including hepatocellular carcinoma (HCC). However, few studies have focused on the direct interaction of these factors on in vivo tumour development and angiogenesis. AIM: To examine the interaction between both factors in murine HCC. METHODS: We examined the combination effect of VEGF and Ang-2 overexpression by means of a combination of a retroviral tetracycline (tet) regulated gene manipulating system in vivo, by providing tet in the drinking water, and a conventional plasmid gene expression system. RESULTS: Neither Ang-2 nor VEGF overexpression induced proliferation of HCC cells in vitro. In vivo, although overexpression of Ang-2 did not increase tumour development, simultaneous expression of Ang-2 and VEGF synergistically augmented tumour growth and angiogenesis in murine HCC. Ang-2 plus VEGF induced tumour development was markedly attenuated by treatment with neutralising monoclonal antibodies against VEGF receptors. Ang-2 plus VEGF overexpression significantly increased the activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the tumour. Suppression of intratumoral VEGF almost completely abolished this augmentation of MMPs. CONCLUSIONS: These results suggest that Ang-2 synergistically augments VEGF mediated HCC development and angiogenesis. This proangiogenic activity was exerted only in the presence of VEGF, at least partly mediated via induction of MMP-2 and MMP-9 in the tumour.

Successful treatment of acute Budd-Chiari syndrome with percutaneous transluminal angioplasty.

A 26-year-old man developed progressive, massive ascites and hematemesis due to rupture of esophageal varices. Combination diagnostic modalities of color doppler ultrasonography, enhanced computed tomography, and magnetic resonance imaging led to the case being diagnosed as acute Budd-Chiari syndrome with severe stricture of the intrahepatic inferior vena cava. Percutaneous transluminal angioplasty this resulted in great improvement of the clinical manifestations.

Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis.

BACKGROUND: It has been shown that expression of the potent angiogenic factor, vascular endothelial growth factor (VEGF), and its receptors, flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), increased during the development of liver fibrosis. AIMS: To elucidate the in vivo role of interaction between VEGF and its receptors in liver fibrogenesis. METHODS: A model of CCl(4) induced hepatic fibrosis was used to assess the role of VEGFR-1 and VEGFR-2 by means of specific neutralising monoclonal antibodies (R-1mAb and R-2mAb, respectively). R-1mAb and R-2mAb were administered after two weeks of treatment with CCl(4), and indices of fibrosis were assessed at eight weeks. RESULTS: Hepatic VEGF mRNA expression significantly increased during the development of liver fibrosis. Both R-1mAb and R-2mAb treatments significantly attenuated the development of fibrosis associated with suppression of neovascularisation in the liver. Hepatic hydroxyproline and serum fibrosis markers were also suppressed. Furthermore, the number of alpha-smooth muscle actin positive cells and alpha1(I)-procollagen mRNA expression were significantly suppressed by R-1mAb and R-2mAb treatment. The inhibitory effect of R-2mAb was more potent than that of R-1mAb, and combination treatment with both mAbs almost completely attenuated fibrosis development. Our in vitro study showed that VEGF treatment significantly stimulated proliferation of both activated hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). VEGF also significantly increased alpha1(I)-procollagen mRNA expression in activated HSC. CONCLUSIONS: These results suggest that the interaction of VEGF and its receptor, which reflected the combined effects of both on HSC and SEC, was a prerequisite for liver fibrosis development.

Penetration of minocycline hydrochloride into lung tissue and sputum.

Penetration of minocycline hydrochloride (MINO) into lung tissue and sputum was investigated. MINO (100 mg) was intravenously infused over 30 min to 14 patients before lung surgery: the concentration of MINO was determined in 16 lung tissue samples which were collected between 0.25 and 5.0 h after infusion. The mean concentration of MINO in lung tissue sample was 2.92 +/- 1.43 microg/g, and the mean lung tissue/plasma ratio of MINO concentration was 3.71 +/- 2.36. MINO was infused intravenously over 60 min twice daily to 5 patients with a chronic respiratory disease for 3-7 days. The concentration of MINO in sputum and in serum was determined on day 3. The mean maximum concentration of MINO in sputum sample was 2.12 +/- 2.20 microg/g, and the mean sputum/serum ratio of MINO concentration was 0.56 +/- 0.47. The concentration of MINO in sputum showed little time-related variation and remained as high as 0.74 microg/g until 10 h after infusion. The concentration of MINO in sputum and in serum after intravenous drip infusion was about twice as high as that after oral administration at the same dose. The breakpoint was 1.88 for MINO, as calculated by the formula established by the Japan Society of Chemotherapy.

[A comparative study of the prognosis for Japanese patients with idiopathic interstitial pneumonia or BOOP based on histopathologic subsets].

We explored the prognosis for 123 patients with either idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). All patients underwent either open lung biopsy or thoracoscopic lung biopsy procedures. The histopathologic diagnosis of IIP included patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and desquamative interstitial pneumonia with respiratory bronchiolitis-associated interstitial lung disease. The prognosis was poorest for patients with a histologic diagnosis of UIP, and excellent for those who received a diagnosis of BOOP. Although the prognosis is generally considered to be good for patients with NSIP, some NSIP patients in our study died. Histopathologic diagnosis based on surgical lung biopsy is useful in evaluating the prognosis for patients with IIP.

Identification and characterization of a deletion mutant of DNA topoisomerase I mRNA in a camptothecin-resistant subline of human colon carcinoma.

In previous studies, we established two camptothecin (CPT)-resistant sublines, HT-29 / CPT and St-4 / CPT, from the human colon cancer cell line HT-29 and the human stomach cancer cell line St-4, respectively. Cellular contents of DNA topoisomerase I (topo I) in the resistant cells were eight-fold less than those in the corresponding parental lines. In this study, we have shown expression of two species of the TOP1 mRNA in HT-29 / CPT. The longer mRNA (4.0 kb) is the wild-type TOP1 mRNA, and the shorter mRNA (3.3 kb) proved to have a deletion of 672 bp (nucleotides 58 - 729 or 59 - 730) that caused the in-frame deletion of amino acids 20 - 243 of human topo I. The deleted region is identical to exons 3 - 9 of the TOP1 gene. The expression level of the 3.3-kb mRNA was similar to that of the wild-type mRNA in HT-29 / CPT. St-4 / CPT expressed only the wild-type TOP1 mRNA in lesser amounts than did St-4. Mouse NIH3T3 cells transfected with the wild-type TOP1 cDNA showed higher sensitivity to CPT than the parental cells, whereas those transfected with the deleted TOP1 cDNA showed levels similar to those of the parental cells. Expression of the exogenous TOP1 mRNA was confirmed; however, expression of the truncated topo I was not detected in cells transfected with the deleted TOP1 cDNA. These results suggest that the expression of the deleted TOP1 mRNA led to the low expression of CPT-sensitive topo I in the resistant cells.

Selection of specific phage from display libraries: monoclonal antibody against VCS M13 helper phage coat protein III (gIIIp).

Screening of specific phage is often hampered by nonspecific binding either of the VCS M13 helper phage to the solid phase absorbent or to the polyclonal antibodies used for selection. The former is improved by increasing the stringency for selection. However, the available polyclonal anti-VCS M13 antibodies often react with immobilized antigen nonspecifically, making it difficult to distinguish between positive and negative clones. To improve this selection process, a monoclonal antibody (MAb) was produced which recognizes ligand-coat protein three (gIIIp) on the helper phage VCS M13. This MAb is highly sensitive and specific, and it is useful for selecting relevant clones. This reagent should find widespread application in identifying interactive clones from a variety of phage display libraries.

Retroviral expression of a mutant (Gly-533) human DNA topoisomerase I cDNA confers a dominant form of camptothecin resistance.

In previous studies, we isolated a mutant DNA topoisomerase I cDNA from a camptothecin (CPT)-resistant human T-lymphoblastic leukemia cell line, CPT-K5, and demonstrated that an amino acid change from Asp to Gly at residue 533 is responsible for the CPT resistance of the enzyme. In the present study, we have constructed a bicistronic retroviral vector, Ha-TM1-IRES-neo, that carries the mutant (Gly-533) TOP1 cDNA (TM1) and a neomycin-resistance gene to examine the effect of mutant DNA topoisomerase I (topo I) expression on CPT resistance of cells. HeLa S3 cells were transduced with Ha-TM1-IRES-neo, and the transduced cells were selected with G418. Two independently isolated populations of the G418-resistant cells and 2 clones showed 1.7- to 1.8-fold higher resistance to CPT than the control cells. Integration and expression of the exogenous TOP1 were confirmed by genomic and RT-PCR analyses. The topo I enzyme (mixture of mutant and wild-type) expressed in the transduced cells showed 3-fold resistance to CPT in cleavable-complex-formation assay and DNA-relaxation assay. Mutant topo I activity in the transduced cells was as much as 10% that of the endogenous enzyme. Our results clearly show that expression of Gly-533 topo I confers a dominant form of CPT resistance in cells expressing wild-type topo I. The mutant TOP1 could be used for the protection of normal bone marrow cells of cancer patients from the severe hematotoxicity of CPT-derivative anti-tumor agents.

[Percutaneous drainage of a bulla with tuberculous infection in a patient].

A 63-year-old man complaining of low grade fever and dry cough was admitted to our hospital. Chest X-ray showed infiltrative shadows and a bulla with a fluid level in the left upper lung field. Bacteriological examination of sputum and bronchoalveolar lavage fluid did not yield any diagnostic results. Percutaneous aspiration of the bulla under fluoroscopy was performed. Bulla with tuberculous infection was considered because a high ADA level was detected in the fluid of the bulla. A culture of the bulla fluid was positive for mycobacterium tuberculosis (TB), which was sensitive to all anti-mycobacterial drugs. The fluid in the bulla gradually increased, and occupied the entire space of the bulla three months later. Percutaneous aspiration of the bulla was performed again and a fluid smear was positive for TB. It was thought that systemic administration of anti-mycobacterial drugs had been ineffective, so percutaneous drainage and subsequent injection of anti-mycobacterial drugs into the bulla was performed. The fluid in the bulla subsequently disappeared and the bulla shrank gradually. Percutaneous drainage of a bulla with tuberculous infection should be considered in those who do not respond to medical management.

Receptor-mediated cellular entry of nuclear localizing anti-DNA antibodies via myosin 1.

A unique subset of anti-DNA antibodies enters living cells, interacts with DNase 1, and inhibits endonuclease activity, before their nuclear localization and subsequent attenuation of apoptosis. We now report that endocytosis of these immunoglobulins is mediated by cell surface binding to brush border myosin (myosin 1). Cellular entry and internalization via this unique receptor provides initial contact for entry and sorting these immunoglobulins to translocate to the nuclear pore and enter the nucleus, interact with DNase 1 within the cytoplasm, or recycle back to the cell surface. This internalization pathway provides clues to the translocation of large proteins across cell membranes and the functional effects of intracellular antibodies on cytopathology. This is the first demonstration that brush border myosin functions as a specific cell surface receptor for internalization of large proteins.

[Two cases of tubercle bacilli infected pulmonary bulla].

Two cases of tubercle bacilli infected bulla are reported. Case 1; A 78-year-old man visited our hospital complaining of fever and chest pain. The chest radiograph revealed the bulla with air fluid level in the left upper lung field. Mycobacterium tuberculosis was detected in the fluid obtained by percutaneous lung aspiration. He was treated with anti-mycobacterial drugs and showed improvement. Case 2; A 66-year-old man visited our hospital complaining of fever, chest pain and dry cough. The chest radiograph revealed the bulla with air fluid level in the left upper lung field. A diagnosis of tubercle bacilli infected bulla was considered because of high level of ADA in the fluid obtained by percutaneous lung aspiration, and anti-mycobacterial drugs were administered. His symptoms were improved and the frequent chest radiograph showed gradual absorption of the fluid. It is suggested that ADA and bacteriological examinations of the fluid obtained by percutaneous lung aspiration are useful for early diagnosis of tubercle bacilli infected bulla.

Nuclear proteins involved in cell division in the ciliate, Tetrahymena.

For the purpose of clarifying the presence of nuclear proteins which may induce cell division, we conducted experiments using ciliate Tetrahymena which can be synchronized at the G2 phase in the cell cycle easily by periodic heat shock treatment (HST): We obtained proteins from the nuclei isolated from the cells grown at the early mid log-phase, at the G2 phase (60 min) and at the G1 phase (150 min), after HST. The proteins were studied by comparing the spots separated by isoelectric point, 10-20% gradient SDS two-dimensional electrophoresis. As a result, in comparison with the intranuclear protein at the log-phase, the proteins at the G2 phase showed a marked increase, but with no great change in the electrophoretic pattern. Meanwhile, the proteins at the G1 phase differed greatly from those at the G2 phase not only in the quantitative changes, but in the electrophoretic patterns. It is considered that the level of the accumulation of the nuclear proteins which should be closely involved in cell division must increase markedly at the G2 phase and decrease at the G1 phase. We confirmed the presence of four proteins: pI 5.8 MW 68 kDa, pI 6.1 MW 75 kDa, pI 8.6 MW 48 kDa and pI 6.6 MW 57 kDa, and then prepared monoclonal antibodies using these nuclear proteins as antigens. Among them, the antibody (IgM) against the pI 8.6 MW 48 kDa polypeptide (p48) was recognized the nuclei by indirect immunofluorescence in ancellular system at the S, G2 and the mid-M phases. However, nuclei at the late M and G1 phases were not stained.(ABSTRACT TRUNCATED AT 250 WORDS)