Cure of malignant ascites and generation of protective immunity by monoclonal antibody-targeted activation of a glucuronide prodrug in rats

We examined the in vivo efficacy of targeting beta-glucuronidase (betaG) to activate a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at hepatoma ascites in Sprague-Dawley rats. Injection i.p. of 500 microg RH1-betaG, a conjugate formed between recombinant betaG and monoclonal antibody RH1 with specificity for an antigen expressed on AS-30D rat hepatoma cells, into rats bearing AS-30D ascites resulted in the accumulation of 54 microg conjugate per 10(9) tumor cells after 2 hr. Ascites fluid and serum contained 0.53 and 0 microg/ml, respectively, RH1-betaG 2 hr after injection of the conjugate. Conjugate binding to AS-30D cells was heterogeneous and non-saturated, as determined by flow cytometry. BHAMG was less toxic than pHAM to SD rats based on measures of animal mortality, weight loss and hematological toxicity. Treatment of rats bearing established hepatoma ascites with 500 microg RH1-betaG followed 2 hr later with a single i.p. injection of 30 mg/kg BHAMG or 3 i.p. injections of 10 mg/kg BHAMG 2, 3 and 4 hr later resulted in the cure of 6/8 and 8/8 animals, respectively. Treatment with BHAMG or pHAM alone did not produce cures, whereas treatment with a control antibody-betaG conjugate and BHAMG produced significantly greater hematological toxicity compared to treatment with RH1-betaG and BHAMG. All cured rats were completely protected from rechallenge with 2 x 10(7) AS-30D cells, indicating that successful treatment of animals induced protective immunity.     

Partial congenital defect of the left pericardium: angiographic diagnosis and treatment by thoracoscopic pericardiectomy: case report

Twenty-six patients with an intracardiac myxoma underwent surgical resection at our institution from 1977 through 1992. Left atrial myxoma was diagnosed in 22 patients, left ventricular in 1, right atrial in 2, and right ventricular in 1. Six patients were asymptomatic; preoperative symptoms included dyspnea, arrhythmias, embolic episodes, and syncope. The diagnosis was established with transthoracic echocardiography in all cases but one. Surgery was performed in all cases with the aid of cardiopulmonary bypass with moderate hypothermia and cold crystalloid cardioplegia. One patient with a left ventricular myxoma died in a comatose state during the immediate postoperative period. Long-term clinical and echocardiographic evaluation was performed in 19 patients; results were excellent (all the patients were in New York Heart Association functional class I or II), and no recurrences were documented. The clinical characteristics, diagnostic methods, and surgical approach are presented and discussed.     

Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters

Amounts of hepatotoxic microcystin and neurotoxic anatoxin-a were estimated in natural blooms and strains of cyanobacteria from freshwaters in Japan. A simultaneous analysis method of anatoxin-a and microcystin was applied to natural bloom samples, which has been dominated by several species and the strains of cyanobacteria which produced simultaneously both toxins. The natural blooms examined in the present study were mainly composed of Anabaena and Oscillatoria, but most also contained Microcystis and other cyanobacteria. Only one sample was almost unialgal, Anabaena spiroides, collected from Lake Sagami. The toxins in 14 samples collected from nine different natural blooms during 1988-1992 were identified as microcystins-RR, -YR, and -LR; desmethyl-7-microcystin-LR (7-DMLR); and anatoxin-a. Microcystins were the main toxins contained in these natural blooms, with anatoxin-a not being detected or of very little quantity. 7-DMLR was detected in samples only from Lake Kasumigaura. Five strains of Anabaena isolated from waters in Japan produced a small amount of anatoxin-a, but no microcystins. One half of the strains of Microcystis produced microcystins and/or anatoxin-a. This is the first study showing Microcystis producing both anatoxin-a and microcystins.     

Copy number differences in the 195 bp repeated satellite DNA from Trypanosoma cruzi and Trypanosoma rangeli: potential use for epidemiologic surveys

Detection of a nondistended pyriform sinus on cross-sectional imaging studies represents a diagnostic dilemma. The finding may be an inconstant physiologic phenomenon without clinical significance, or it may be due to tissue thickening and lack of pliability related to neoplasia or inflammation. Rescanning during respiratory maneuvers may clarify the anatomy, but full patient cooperation is needed. We demonstrate a method (turning the patient's head away from the side of the nondistended sinus) that induces distention of the pyriform sinus but does not require active patient participation.     

Uncooled DBR laser directly Modulated at 3.125 gb/s as athermal transmitter for low-cost WDM systems

An uncooled three-section tunable distributed Bragg reflector laser is demonstrated as an athermal transmitter for low-cost uncooled wavelength-division-multiplexing (WDM) systems with tight channel spacing. A /spl plusmn/0.02-nm thermal wavelength drift is achieved under continuous-wave operation up to 70/spl deg/C. Dynamic sidemode suppression ratio of greater than 35 dB is consistently obtained under 3.125-Gb/s direct modulation over a 20/spl deg/C-70/spl deg/C temperature range, with wavelength variation of as low as /spl plusmn/0.2 nm. This indicates that more than an order of magnitude reduction in coarse WDM channel spacing is possible using this source.     

SQUID NMR Studies of the Second Layer of 3He at High Density

Nuclear magnetism in the second layer of ³He films on graphite has been studied as a function of density in the zero-field limit at temperatures down to 300 µK. Total surface coverages in this study ranged from 20 atoms/nm² (the lowest coverage at which the effective exchange parameter turns ferromagnetic) through the two-phase region (ending at about 24 atoms/nm²) and into the single-phase imcommensurate solid region up to 31.2 atoms/nm². The surface layers were studied using both pulsed and cw NMR measured with our SQUID NMR system in magnetic fields of 500 µT and lower. As the surface density continues to increase in the single-phase region, the exchange constant decreases consistently with a picture of steric hindrance impeding ferromagnetic exchange. Several different observational features scale with this inferred exchange: low-field magnetization, NMR frequency shift, and the temperature of onset of significant magnetization.     

Effect of sampling density on the measurement of stream condition indicators in two lowland Australian streams

There is widespread application of indicators to the assessment of environmental condition of streams. These indicators are intended for use by managers in making various comparative and absolute assessments and often have a role in resource allocation and performance assessment. Therefore, the problem of formally defining confidence in the results is important but difficult because the sampling strategies used are commonly based on a compromise between the requirements of statistical rigour and the pragmatic issues of access and resources. It is rare to see this compromise explicitly considered and consequently there is seldom quantification of the uncertainty that could affect the confidence a manager has in an indicator. In this paper, we present a method for quantitatively assessing the tradeoffs between sampling density and uncertainty in meeting various monitoring objectives. Assessments using judgement‐based representative reaches are shown to be unreliable; instead a sampling approach is recommended based on the random selection of measuring sites. A detailed dataset was collected along two streams in Victoria, Australia, and the effect of sampling density was assessed by subsampling from this dataset with precision related to the number of sites assessed per reach length and the intensity of the sampling at each site. The sampling scheme to achieve a given precision is shown to depend on the monitoring objective. In particular, three objectives were considered: (1) making a baseline assessment of current condition; (2) change detection; and (3) detection of a critical threshold in condition. Change detection is shown to be more demanding than assessing baseline condition with additional sampling effort required to achieve the same precision. Sampling to detect a critical threshold depends on nominating acceptable values of Type I and II error and the size of the effect to be detected. Copyright © 2006 John Wiley & Sons, Ltd.