No fitness cost of glyphosate resistance endowed by massive EPSPS gene amplification in Amaranthus palmeri.

Amplification of the EPSPS gene has been previously identified as the glyphosate resistance mechanism in many populations of Amaranthus palmeri, a major weed pest in US agriculture. Here, we evaluate the effects of EPSPS gene amplification on both the level of glyphosate resistance and fitness cost of resistance. A. palmeri individuals resistant to glyphosate by expressing a wide range of EPSPS gene copy numbers were evaluated under competitive conditions in the presence or absence of glyphosate. Survival rates to glyphosate and fitness traits of plants under intra-specific competition were assessed. Plants with higher amplification of the EPSPS gene (53-fold) showed high levels of glyphosate resistance, whereas less amplification of the EPSPS gene (21-fold) endowed a lower level of glyphosate resistance. Without glyphosate but under competitive conditions, plants exhibiting up to 76-fold EPSPS gene amplification exhibited similar height, and biomass allocation to vegetative and reproductive organs, compared to glyphosate susceptible A. palmeri plants with no amplification of the EPSPS gene. Both the additive effects of EPSPS gene amplification on the level of glyphosate resistance and the lack of associated fitness costs are key factors contributing to EPSPS gene amplification as a widespread and important glyphosate resistance mechanism likely to become much more evident in weed plant species.

Alpha-glucosidase inhibitors with a 4,5,6,7-tetrachlorophthalimide skeleton pendanted with a cycloalkyl or dicarba-closo-dodecaborane group.

Previous studies of alpha-glucosidase inhibitors derived from thalidomide revealed that 4,5,6,7-tetrachloro-N-alkylphthalimide derivatives are superior lead compounds. Structure-activity relationship studies indicated that a hydrophobic group at the N(2) position is mandatory for potent activity. Accordingly, we have designed and synthesized some 4,5,6,7-tetrachloro-N-cycloalkylphthalimide and 4,5,6,7-tetrachloro-N-dicarba-closo-dodecaborane derivatives. The prepared compounds exhibited potent alpha-glucosidase-inhibitory activity. Among them, 4,5,6,7-tetrachloro-N-cycloheptylphthalimide (9) showed the most potent activity, being approximately 30 times more active than the classical inhibitor, 1-deoxynojirimycin (1).

Cysteine string proteins are associated with cortical granules of Xenopus laevis oocytes.

Cysteine string proteins (csps) are associated with secretory organelles in a wide range of eukaryotic cells. Functional studies of these proteins indicate that they subserve one or more vital steps in the pathway of regulated exocytosis. Here, we document the presence of csps in fully grown (stage VI) oocytes of the frog, Xenopus laevis. Both Northern and immunoblot data support the conclusion that csps are expressed in these cells. In addition, immunoreactive csp is seen even at the earliest stage of oocyte development, namely, in stage I oocytes. Finally, immunoblot and immunocytochemical results indicate that csps are associated with cortical granules of stage II-VI oocytes. These observations suggest that csps participate in the cortical reaction that underlies the sustained block to polyspermy in Xenopus eggs. Moreover, because of the relative ease of manipulating cells as large as Xenopus oocytes, this system harbors considerable promise as a model for studying the role of csps and other proteins in exocytotic events.

Alpha-glucosidase inhibitors with a phthalimide skeleton: structure-activity relationship study.

Alpha-glucosidase inhibitors with a phthalimide skeleton were prepared. Structure-activity relationship studies indicated a critical role for the hydrophobicity of the substituent at the nitrogen atom of the phthalimide skeleton. Introduction of electron-withdrawing groups, including a nitro group and chlorine, influenced the activity. Optimization studies led us to design 4,5,6,7-tetrachloro-N-phenylphthalimide (CPOP) and its N-phenylalkyl derivatives. CP0P and 4,5,6,7-tetrachloro-N-(4-phenylbutyl)phthalimide (CP4P) proved to be more potent alpha-glucosidase inhibitors than the known inhibitor 1-deoxynojirimycin.

Novel alpha-glucosidase inhibitors with a tetrachlorophthalimide skeleton.

Novel alpha-glucosidase inhibitors with a tetrachlorophthalimide skeleton were prepared and their structure-activity relationships were analyzed. Among them, N-phenyl-4,5,6,7-tetrachlorophthalimide (CPOP: 2) and N-(4-phenylbutyl)-4,5,6,7-tetrachlorophthalimide (CP4P: 6) showed very potent inhibitory activity, being more potent than 1-deoxynojirimycin (dNM: 1). Mechanistic studies revealed that CPOP (2) and CP4P (6) inhibit alpha-glucosidase non-competitively and competitively, respectively.

Long-term outcome of endoscopic balloon dilation in obstructive gastrointestinal Crohn's disease: a prospective long-term study.

Background The short- and long-term results of balloon dilation therapy in Crohn's patients with non-anastomotic obstructive gastrointestinal lesions are investigated.Materials and methods Fifty-five patients with Crohn's disease who had obstructive gastrointestinal lesions were treated prospectively by endoscopic balloon dilation.Short-term results Eight of the initial dilations were unsuccessful giving no symptomatic relief (14.5%).Long-term results The subjects of the long-term prognosis were 40 cases followed up for more than 6 months (average 37 months) and their strictures were non-anastomotic in more than half (59%). Avoidance of surgery, was possible in 31 of 40 patients (78%). Surgery was avoided in 92%, 81% and 77% of patients after one, two, and three years, respectively (Kaplan-Meier's method). There was no difference in long-term outcome between anastomotic strictures and strictures in the absence of prior surgery.Conclusion Our results suggest that, (1) strictures in the absence of prior surgery might be treated in this way as well as anastomotic strictures; (2) if followed for a prolonged time period, more than 70% of patients, who have undergone balloon dilation for obstructive gastrointestinal Crohn's disease, may be able to avoid surgery.

Preoperative detection of occult enterovesical fistulas in patients with Crohn's disease: efficacy of oral or rectal administration of indocyanine green solution.

OBJECTIVES: Nonhazardous enteral administration of indocyanine green solution was performed to detect enterovesical occult microfistulas in patients with Crohn's disease before the fistulas had become readily apparent. METHODS: A total of 12 patients with Crohn's disease who were suspected from their clinical manifestations of having enterovesical fistulas underwent study. For detection of the fistulas after oral or rectal administration of the indocyanine green solution, urine was collected and examined using a colorimeter to check for contamination with indocyanine green. The effectiveness of the indocyanine green test and conventional x-ray study was compared. RESULTS: The indocyanine green test was positive after either oral or rectal administration in 11 of the 12 patients, providing a rate of accurate diagnosis of 92 percent (11/12 patients). In contrast, the rate of accurate diagnosis using the x-ray study was only 17 percent (2/12 patients). Furthermore, in eight patients with occult fistulas, accurate diagnosis could be made in none using the x-ray study, whereas all showed positive results with use of the indocyanine green test. CONCLUSIONS: The ability to diagnose obscure fistulas using the indocyanine green test was 92 percent. This indocyanine green test was highly diagnostic, whereas conventional examinations are often complicated and much less diagnostic.

[A case of recurrent ovarian cancer successfully treated with etoposide].

A 49-year-old woman with recurrent ovarian cancer clear cell carcinoma was treated by etoposide. The recurrence was found seven months after second operation. The etoposide (50 mg/day per os) was first given for 2 weeks and then etoposide (25 mg/day per os) for 4.5 months. After one month of treatment the target tumor mass was reduced in size, and the therapy was continued for 4 months in our Outpatient Department. A partial response was confirmed by B-Scope, and the tumor marker CA-125 was reduced to 15 U/ml from 210 U/ml before treatment. No side effects were observed in the patient. This case suggests that etoposide might be effective for recurrent ovarian cancer and the whole treatment course could be handled in the Outpatient Department.

Prenatal diagnosis of partial trisomy 22 derived from a maternal t(11; 22) (q23; q11).

A fetus with partial trisomy 22 was detected by amniocentesis in a pregnant woman with balanced translocation, 46, XX, t(11; 22) (q23; q11). The aborted fetus had multiple congenital anomalies consisting of microcephaly, cleft lip and palate. The extra acrocentric chromosome was identified as der (22), t(11; 22) (q23; q11). The aborted fetus is compared with other trisomic cases described in literatures, and perinatal diagnosis of this case was discussed.

Spontaneous and MMC induced SCE in lymphocytes from patients with cervical cancer.

The frequencies of spontaneous and mitomycin C (MMC) induced sister chromatid exchanges (SCEs) were investigated in lymphocytes of the peripheral blood of women in different stages (O-III) of cervical cancer. Average generation time (AGT) was also examined by the replicative index (R.I.) method. The following results were obtained: The spontaneous SCE frequency was found to be significantly higher in the cancer group than in the control group; 8.21 +/- 1.42 (mean +/- S.D.) against 5.62 +/- 0.55. The SCE frequency gradually increased with the progression of the cervical cancer. The SCE frequency in patients with carcinoma in situ (CIS), the lowest stage of cervical cancer, was significantly higher than that of the controls. The frequency of MMC induced SCE was higher than that of spontaneous SCE in all groups, and the difference in frequency between MMC induced and spontaneous SCEs of cervical cancer group of the stages I-III was significant by different from that of the control group. The AGT of the cervical cancer group was shorter than that of the control group, but it was not statistically significant.

Influence of pulse-wave ultrasonic irradiation on the prenatal development of mouse.

C3H/He mouse embryos in utero were exposed to intensepulsed ultrasound on the 8th day of gestation (VP day = 0). Fetal anomaly was observed in mice exposed for 5 min to 58.6 W/cm2 peak intensity pulsed ultrasound, but not in those of a group exposed to a reduced peak intensity having the same pulse width and repetition frequency. In spite of similar average acoustic intensities, the group exposed to the higher intensity (59.4 W/cm2) exhibited fetal anomaly. There was no fetal anomaly in the lower peak intensity group. No increase in fetal anomay was observed after exposure to ultrasound having a smaller pulse width (3 microseconds), even though the peak intensity was 56.3 W/cm2. It is suggested that teratogenecity may depend on both the peak intensity and the pulse width of the ultrasound. Critical acoustic intensity on the 8th day of pregnancy in mice is estimated to be 60 W/cm2 SATP and 1.2 W/cm2 SPTA values.

Chromosome analysis in couples with recurrent abortions.

Chromosome analysis using a G-Banding technique was performed in 35 couples (70 individuals) with a history of two or more spontaneous abortions of unknown cause. Among these individuals, 5 (7%) showed balanced translocations, all of whom were female. The outcome of 31 pregnancies of 10 balanced translocation carriers was as follows: Ten of the offspring had normal phenotypes (32%), 5 (16%) were born with chromosomal abnormalities and 16 (52%) were spontaneously aborted.