Phase I and pharmacokinetic trial of carboplatin in refractory adult leukemia.

Sixteen patients [13 acute nonlymphocytic leukemia (ANLL), 2 acute lymphocytic leukemia, 1 chronic myelogenous leukemia in a blast crisis; median age, 40 yr; range, 25-78 yr; 9 male, 7 female] received 23 courses of carboplatin given as a bolus on a daily X 5 schedule. Six patients were given 7 courses of carboplatin at 200 mg/m2/day; 3 patients received 5 courses at 250 mg/m2; 9 patients received 11 courses at 300 mg/m2; 2 patients initially treated at 200 mg/m2 were given their 2nd course at 300 mg/m2. Significant hearing loss documented by audiometry occurred in five patients, including three of nine treated at 300 mg/m2. All five had prior or recent exposure to aminoglycoside antibiotics. Three patients developed cancer and acute leukemia group B grade 3 or 4 mucositis, and 18 of 23 courses were complicated by nausea and vomiting. Marrows were hypocellular or aplastic in all patients treated at the highest dose. No complete responses occurred, although two patients with ANLL treated at 300 mg/m2 achieved partial responses lasting 71 and 138 days. The t1/2 alpha [half-life (t1/2)], t1/2 beta, and total body clearance of ultrafilterable platinum were comparable to those previously described by us in patients receiving bolus doses of carboplatin of 22-77 mg/m2/day X 5. Carboplatin has activity in ANLL.

A novel experimental apparatus to study the impact of white noise and 1/f noise on animal populations.

This paper reports on the design and construction of a novel apparatus that allows a set of aquatic microcosms to experience complex temporal environmental fluctuations. Replicate microcosms were maintained in 18 water baths with independent environmental controls. We give results from a preliminary experiment designed to look at the effects of varying temperatures with different variance spectra (i.e. white noise or 1/f noise) on single species population dynamics. Matching time series (with identical elements, differently ordered) of environmental temperatures with different Fourier spectra were created for use as input to the apparatus using a novel spectral mimicry method. The apparatus functioned well during the course of the experiment making this an extremely useful research tool. This apparatus now provides ecologists with a means of studying how environmental variability and directional trends in this variability, are filtered and translated by real populations and micro-ecosystems.

Sulfacytine in uncomplicated urinary tract infections. Double-blind comparison with sulfisoxazole.

A new sulfonamide, sulfacytine, was compared in a double-blind study with sulfisoxazole in 132 patients with uncomplicated urinary tract infections. At the doses used, 1Gm. per day of sulfacytine of 4 Gm. per day sulfisoxazole, bacteriologic success (decrease of pathogenic organisms from greater than or equal to 100,000 to less than or equal to 1,000 per milliliter of urine) was demonstrated in approximately 90 per cent of the patients. Clinical success (subsidence of the symptoms, frequency of urination, and dysuria, and reduction of pyuria from greater than or equal to 10 to less than 10 white blood cells per high-power field) occurred in 85 to 90 per cent. Six patients in the sulfacytine group and 9 in the sulfisoxazole group reported adverse experiences. Drug was discontinued or administration interrupted because of adverse experiences in 4 sulfacytine patients and 6 sulfisoxazole patients. Laboratory values generally remained normal, but 1 patient in each medication group had decreases in white blood cells that might have been attributable to drug. On the basis of this study sulfacytine appears to be an effective drug for the treatment of uncomplicated urinary tract infections.

Meal-taking behavior is related to predisposition to dietary obesity in the rat.

The hypothesis that early nutritional experience can determine endogenous patterns of meal-taking behavior and thereby affect predisposition to dietary obesity was tested by raising male Sprague-Dawley rats in litters of 4, 8, and 20, and examining their meal patterns and responsiveness to a high-fat, high-sugar (HFS) diet in adulthood. At 9 months of age, half the rats from each litter size group were given the HFS diet for 16 weeks, while the other half were continued on laboratory chow. As expected, HFS-fed rats gained more weight and developed larger fat depots and more and larger fat cells than did chow-fed controls. Analysis of meal-taking behavior just prior to the introduction of HFS-feeding allowed some of the rats to be classified as "gorgers" or "nibblers" according to their average daily meal size. While on lab chow, gorgers and nibblers showed no differences in body weight gain, but upon being switched to the HFS diet, gorgers gained significantly more weight than did nibblers, and showed a greater degree of fat depot enlargement. These findings suggest that patterns of meal-taking behavior can predict the magnitude of and may contribute to the development of dietary obesity.

Evaluation of a rapid and automated enzyme-linked fluorescent immunoassay for detecting Escherichia coli serogroup O157 in cheese.

The Vitek Immunodiagnostic Assay System (VI-DAS) for Escherichia coli O157, a rapid and fully automated test, was evaluated for use in detecting the foodborne pathogen E. coli O157:H7 in soft, semisoft, and hard cheeses. Sixty-five cheese samples were artificially contaminated at low (2-4 colonyforming units [cfu]/25 g) and high (7-10 cfu/25 g) levels with one of 2 strains of enterohemorrhagic E. coli O157:H7. Contamination at high levels was detected in all cheeses by VIDAS, whereas in 5 cheeses (7.7%) inoculated at low levels, contamination was not detected. In 15 additional cheeses inoculated with cold-stressed cells, both VIDAS and the Bacteriological Analytical Manual cultural assay detected all high and low levels of contamination. No false positives or interference from product background fluorescence was encountered in any of the cheeses tested by VIDAS.

Transmission electron microscopy as a tool for nanocrystal characterization pre- and post-injector.

Recent advancements at the Linac Coherent Light Source X-ray free-electron laser (XFEL) enabling successful serial femtosecond diffraction experiments using nanometre-sized crystals (NCs) have opened up the possibility of X-ray structure determination of proteins that produce only submicrometre crystals such as many membrane proteins. Careful crystal pre-characterization including compatibility testing of the sample delivery method is essential to ensure efficient use of the limited beamtime available at XFEL sources. This work demonstrates the utility of transmission electron microscopy for detecting and evaluating NCs within the carrier solutions of liquid injectors. The diffraction quality of these crystals may be assessed by examining the crystal lattice and by calculating the fast Fourier transform of the image. Injector reservoir solutions, as well as solutions collected post-injection, were evaluated for three types of protein NCs (i) the membrane protein PTHR1, (ii) the multi-protein complex Pol II-GFP and (iii) the soluble protein lysozyme. Our results indicate that the concentration and diffraction quality of NCs, particularly those with high solvent content and sensitivity to mechanical manipulation may be affected by the delivery process.

Structure and thermal vibrations of spermine phosphate hexahydrate from neutron diffraction data at 125 K.

Spermine phosphate hexahydrate crystallizes in space group P2(1)/a with unit-cell dimensions a = 7.931 (1), b = 23.158 (5), c = 6.856 (2) A, and beta = 113.44 (2) degrees at 125 K with unit-cell contents [(C10H30N4)2(4+)(HPO4)4(2-).12H2O]. The packing of spermines and monohydrogen phosphates in this crystal structure has features which may be relevant to the binding of spermine to DNA. Another important structural feature is the presence of channels containing water that is hydrogen bonded as in ice-Ih with disordered protons. The channels occur between sheets of spermine long chains and are also bordered by hydrogen-bonded monohydrogen phosphate chains. The hydrogen-bonding scheme of these water chains proposed on the basis of an earlier X-ray study is now confirmed. Nuclear positions, anisotropic mean-square (m.s.) displacements, an overall scale factor and two extinction parameters (rho and g) were refined using full-matrix least-squares giving values of R(F0(2)) = 0.09, Rw(F0(2)) = 0.11 and S = 1.02. Thermal vibrational analysis revealed that the backbone of the spermine cation can be described as a single rigid segment with a substantial libration of 27 deg2 around the spermine molecular long axis.

Cystoscopy of chemically induced bladder neoplasms in rabbits administered the carcinogen dibutylnitrosamine.

Subcutaneous injection of the carcinogen dibutylnitrosamine into male rabbits led to bladder papillomas, hemangiomas, and carcinomas within 17 to 26 months. The progress of the developing bladder lesions was readily followed by cystoscopy.

Electron transport through thin organic films in metal--insulator--metal junctions based on self-assembled monolayers.

This paper describes an experimentally simple system for measuring rates of electron transport across organic thin films having a range of molecular structures. The system uses a metal--insulator--metal junction based on self-assembled monolayers (SAMs); it is particularly easy to assemble. The junction consists of a SAM supported on a silver film (Ag-SAM(1)) in contact with a second SAM supported on the surface of a drop of mercury (Hg-SAM(2))--that is, a Ag-SAM(1)SAM(2)-Hg junction. SAM(1) and SAM(2) can be derived from the same or different thiols. The current that flowed across junctions with SAMs of aliphatic thiols or aromatic thiols on Ag and a SAM of hexadecane thiol on Hg depended both on the molecular structure and on the thickness of the SAM on Ag: the current density at a bias of 0.5 V ranged from 2 x 10(-10) A/cm(2) for HS(CH(2))(15)CH(3) on Ag to 1 x 10(-6) A/cm(2) for HS(CH(2))(7)CH(3) on Ag, and from 3 x 10(-6) A/cm(2) for HS(Ph)(3)H (Ph = 1,4-C(6)H(4)) on Ag to 7 x 10(-4) A/cm(2) for HSPhH on Ag. The current density increased roughly linearly with the area of contact between SAM(1) and SAM(2), and it was not different between Ag films that were 100 or 200 nm thick. The current--voltage curves were symmetrical around V = 0. The current density decreased with increasing distance between the electrodes according to the relation I = I(0)e(-beta d(Ag,Hg)), where d(Ag,Hg) is the distance between the electrodes, and beta is the structure-dependent attenuation factor for the molecules making up SAM(1). At an applied potential of 0.5 V, beta was 0.87 +/- 0.1 A(-1) for alkanethiols, 0.61 +/- 0.1 A(-1) for oligophenylene thiols, and 0.67 +/- 0.1 A(-1) for benzylic derivatives of oligophenylene thiols. The values of beta did not depend significantly on applied potential over the range of 0.1 to 1 V. These junctions provide a test bed with which to screen the intrinsic electrical properties of SAMs made up of molecules with different structures; information obtained using these junctions will be useful in correlating molecular structure and rates of electron transport.