Flow karyotypes and chromosomal DNA contents of genus Triticum species and rye (Secale cereale)

The flow cytometry and chromosome imaging method were jointly used for analyzing genome content and chromosomal DNA content of hexaploid wheat (AABBDD), hexaploid triticale (AABBRR), tetraploid wheat (AABB), and AA, BB, DD genome donors and RR genome rye. Their genome sizes were 34.4 pg, 40.9 pg, 26.2 pg, 12.1 pg, 13.7 pg, 10.5 pg, and 16.9 pg, respectively. The 2C nuclear DNA content of BB genome donor with 13.7 pg was the highest value among the other genome donors, AA or DD. The genome content of tetraploid wheat, unlike hexaploid wheat or hexaploid triticale, was larger than the sum of the genomes of AA and BB genome donors. The DNA content of each chromosome ranged from 1.22 pg in DD genome donor to 2.61 pg in rye. Each chromosome peak was divided into three to four groups. Only one chromosome was included in the highest chromosomal DNA peak in hexaploid wheat, tetraploid wheat, DD genome donor and rye but two chromosomes in AA, BB genome donors, and hexaploid triticale. Correlation between 2C nuclear DNA content and chromosome density volume was the highest value compared with the other chromosomal parameters of chromosome area, or chromosome length.     

Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

The fates of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice

In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, ³H-FX or ³H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given ³H-FX, but mainly via the feces in mice given ³H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of ³H-FX or ³H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in ³H-FX-administered than ³H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with ³H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.     

A Comparison of Two Simple Measures to Evaluate the Health Status of Asthmatics: The Asthma Bother Profile and the Airways Questionnaire 20

Simple and concise measures for health status are desirable in clinical practice. The Asthma Bother Profile (ABP), which consists of 23 items, has been developed to assess how much asthma bothers patients. The Airways Questionnaire 20 (AQ20) is a simple instrument which consists of 20 items. The purpose of this study was to investigate how the ABP and AQ20 evaluate the health status of patients with asthma. A total of 166 patients with chronic asthma (age: 48 ± 16 yr, 77 males) completed pulmonary function testing, measurement of airway hyperresponsiveness, dyspnea rating, assessments of their anxiety and depression (HADS; Hospital Anxiety and Depression Scale), and assessments of their health status. The health status was assessed using the ABP, AQ20, the short-form 36 health survey questionnaire (SF-36), the Living With Asthma Questionnaire (LWAQ) and the Asthma Quality of Life Questionnaire (AQLQ). The Japanese version of the ABP included only 15 'bother' items out of the original 23 items due to cultural differences. The scores on the ABP were widely distributed, whereas the scores on the AQ20 were skewed towards the milder end of the scale. The ABP had a strong correlation with the Avoidance and Distress constructs on the LWAQ, and Anxiety and Depression on the HADS (Rs = 0.56 ∼ 0.79), and its strongest correlation with the General Health (Rs = - 0.64) scale among the 8 subscales on the SF-36. The AQ20 had a less significant correlation with the LWAQ, AQLQ, and SF-36 than the ABP. The ABP and AQ20 were short and simple to complete, and both measures could easily be used in clinical practice. The ABP can evaluate patients more specifically with respect to distress and bother than the AQ20.     

Evaluation of an aortic stent graft for use in surgery on esophageal cancer involving the thoracic aorta

Objective: The purpose of this experimental study was to investigate whether aortic stent grafting can be applied to the treatment of an esophageal cancer involving the thoracic aorta. Methods: The canine thoracic aorta was partially resected without aorta being clamped after emplacement of an endovascular stent graft. Study I; The aortic whole layer of 1 cm in length and 1/4 of the circumference was resected and was covered by a free fascia patch of the abdominal rectal muscle immediately after stent graft placement. Study II; The aortic adventitia and the outer half of the media of the same size was resected on day 3, 7,14, 21, and on day 28, after the stent graft placement. The resected portion was covered by the free fascia patch in half experimental dogs, and was uncovered in the others. Study III; The aortic adventitia and the outer half of the media of 1 cm in length and 1/2 of the circumference was resected and was uncovered on day 7 after stent graft placement. Histological examinations were performed on day 28 and at one year after aortic resection. Results: The aortic wall could be resected in all cases with no complication, except in resection of 1/2 the circumference where the aorta had become narrow. There was no difference in healing of the resected portion of the aorta between with and without fascia covering. Conclusion: An aortic endovascular stent graft could be applied to surgery for an esophageal cancer involving the aorta.     

Successful surgical treatment of secondary kwashiorkor after total gastrectomy: Report of a case

We report herein the case of a 56-year-old woman who developed secondary Kwashiorkor 9 years after undergoing a total gastrectomy for early gastric cancer. Until she began developing the symptoms of Kwashiorkor, including general fatigue, edema of the face and extremities, anemia, alopecia, and weight loss, she had been leading a normal life post-gastrectomy. Her symptoms were alleviated by total parenteral nutrition (TPN) therapy, but reappeared soon after TPN therapy was discontinued. Therefore, she required several subsequent courses of TPN. In an attempt to permanently resolve the ongoing Kwashiorkor symptoms, reconstructive surgery involving transposition of the jejunum from the previous Graham method to the interposition method was performed 10 years after the initial gastrectomy. After the second operation, her malnutrition was completely alleviated, and she has been in good health for the 8 years since. To our knowledge, there has been no other report of the symptoms of secondary Kwashiorkor after total gastrectomy being alleviated by altering the procedure of reconstruction of the intestinal tract. Thus, we recommend surgical treatment to alter the digestive continuity to a more physiological pathway for selected patients with secondary Kwashiorkor syndrome.     

Diffusion Weighting by the Trace of the Diffusion Tensor within a Single Scan

The anisotropy of the water diffusion tensor inside brain causes contrast in diffusion images, which depends on the relative orientation of the diffusion gradients and the subject. Because the trace of a tensor is invariant upon rotation, measurement of this trace can reduce the orientation effect. A family of imaging pulse sequences is presented in which the signal intensity is weighted by the trace of the diffusion tensor in a single scan. The methods are demonstrated for chicken gizzard in several orientations with respect to the gradient frame of reference, and for ischemic injury in cat brain after middle cerebral artery occlusion. The sensitivity of the techniques to the presence of background gradients is measured and discussed in detail. As a result, pulse sequences are suggested that provide reliable diffusion constants in both homogeneous and inhomogeneous magnetic fields. The efficiency of the techniques for clinical application is also evaluated.     

In vivo activity on murine tumors of a novel antitumor compound,N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190)

Summary A novel antitumor compound, N--dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of >200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1–5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a >280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1–5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1–5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a >300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3–10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1–5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3–10), and a >161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3–10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1–5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.Abbreviations ILS increase in life span - MST median survival time - MMC mitomycin C - ADM adriamycin - CPA cyclophosphamide - 5-FU 5-fluorouracil     

Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: role of eosinophils,IL-5, eotaxin,and IL-13

BACKGROUND: Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether glucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established. OBJECTIVE: We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma. METHODS: Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 micro g/kg) and IL-5 (100 micro g/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA. RESULTS: A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexa-methasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent. CONCLUSION: These findings suggest that the inhibition of AHR by the glucocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13.     

Investigation of initial changes in the mouse olfactory epithelium following a single intravenous injection of vincristine sulphate

To investigate initial changes in the olfactory epithelium, vincristine sulphate (VCR) was administered intravenously once to male BALB/c mice on day 1 in comparison with unilateral bulbectomy (UBT). The light and electron microscopy of the olfactory epithelium, nerve and/or bulb with BrdU-morphometry was performed sequentially. Further, whole-body radioluminography was conducted at 1 and 24 hours postdose. Apoptosis and an increased number of mitotic cells with a tendency toward decreasing BrdU-positive olfactory epithelial cell counts were observed in olfactory epithelial cells at 6 hours postdose of VCR and became more pronounced at 24 hours postdose. These changes disappeared on days 4 or 15, but minimal axonal degeneration was seen in the olfactory nerve from day 4 onward. Semiquantitative measurement of VCR levels in the ethmoturbinals elicited high drug retention even 24 hours after administration. In contrast, UBT showed no effect on mitosis and BrdU-positive cell counts at 6 hours postdose, but severe lesions in the olfactory epithelium and nerve were seen on days 2, 4, and/or 15. The above results suggest that the initial event of VCR-induced apoptosis in the mouse olfactory epithelium would be mitotic arrest with high drug retention, unlike that evoked by UBT.