The effects of a monetary alternative on marijuana self-administration

We have used a variety of methods to characterize the genome of the archaeon Methanosarcina thermophila TM-1. Pulsed-field gel analysis indicates a genome size of 2.8 Mb. We have constructed a bacterial artificial chromosome (BAC) library of M. thermophila and have used it to generate physical maps for this organism. The library is made up of 384 clones with an average insert size of 58 kb representing 8.0 genome equivalents. The utility of the library for low-resolution physical mapping was shown by identifying NotI linking clones and using these to order the NotI macrorestriction fragments of M. thermophila into a 2.8 Mb map. Hybridization of nine single copy genes and a 16S rRNA sequence to these macrorestriction fragments forms the basis for the first genetic map in this organism. High-resolution physical maps, consisting of overlapping clones, have been created using HindIII fingerprints of BAC clones. In this way, we identified a minimal path of five clones that span a 270 kb NotI fragment. The ease of manipulating BAC clones makes the BAC system an excellent choice for the construction of low-resolution and high-resolution physical and genetic maps of archaeal genomes. It also provides a substrate for future genome-sequencing efforts.     

Conformational disease

Several diverse disorders, including the prevalent dementias and encephalopathies, are now believed to arise from the same general disease mechanism. In each, there is abnormal unfolding and then aggregation of an underlying protein. The gradual accumulation of these aggregates and the acceleration of their formation by stress explain the characteristic late or episodic onset of the clinical disease. The understanding of these processes at the molecular level is opening prospects of more rational approaches to investigation and therapy.     

Amplified primer extension assay for psoralen photoproducts provides a sensitive assay for a (CG)6TA(CG)2(TG)8 Z-DNA torsionally tuned probe: preferential psoralen photobinding to one strand of a B-Z junction

An amplified primer extension assay has been developed for quantitatively mapping the sites of psoralen photoaddition to DNA. This assay was applied to a torsionally tuned Z-DNA-probe that was specifically designed for the primer extension assay. The torsionally tuned Z-DNA forming sequence, (CG)6TA(CG)2(TG)8, forms Z-DNA in vitro at negative superhelical density: sigma = -0.05. The internal 5'-TA dinucleotide was reactive to psoralen when it existed as B-DNA. Upon the formation of Z-DNA, the internal 5'-TA no longer photobound psoralen. The torsionally tuned sequence was synthesized as an EcoRI fragment such that, when Z-DNA formed, the central 5'-AATT of the EcoRI sites was part of the B-Z junctions. The 5'-AATT sequence was not reactive with psoralen when it existed as B-DNA. When the 5'-AATT sequence existed as a B-Z junction, one strand of each junction became hyperreactive to psoralen. The TT directly 5' to the B-DNA-Z-DNA junction photobound psoralen in a strand-specific fashion. Quantitation of the relative rate of psoralen photobinding to the internal 5'-TA and the 5'-AATT at the B-Z junctions provides relationships that are characteristic of the level of supercoiling in DNA.     

Toward global advancement of medicine: the International Society of Nephrology experience

BACKGROUND: Since its foundation in 1960, the International Society of Nephrology (ISN) has pursued the worldwide advancement of education, science and patient care in nephrology. This goal was achieved by means of the Society's journal and the organization of international congresses and symposia. In order to better reach its colleagues and patients in economically less developed countries, the ISN expanded its activities as of 1980 by a large number of specific programs aimed at these regions. METHODS: The first phase of activities included teaching programs, fellowship and visiting scholar programs, and the provision of travel grants to enhance accessibility to the ISN congresses. A second phase consisted of the creation of a library enhancement program, a commission on acute renal failure and--to improve the organization and efficiency--a central commission on global advancement of nephrology (COMGAN). Currently, a third phase has been entered in which all activities have been intensified: (1) under the guidance of COMGAN, supported by a large number of teaching programs and fact finding missions; (2) by establishing a renal sister program; and (3) by initiating commissions on informatics and on clinical trials. RESULTS: As a result, the ISN has reached most parts of the world, previously deprived of contact with renal science and renal patient care. The fellowship program now counts 160 fellows, who spend one or two years in training. The library enhancement program reaches 218 institutions worldwide. ISN membership has soared over the past two years with over 2,500 new members, mostly in the developing countries. They receive Kidney International and other relevant forms of information. Thus far, 135 pairs of renal units in developing and developed countries have been linked for support on a more continuous basis. ISN-sponsored congresses, symposia, and courses are being held in increasing numbers in the developing world. In many of its activities, the ISN closely collaborates with sister organizations, which also contribute financially. In total, the ISN spends annually over $1 million US from its own budget on the programs described above. CONCLUSION: The various programs and initiatives are proving helpful in advancing renal medicine in areas in need. Expansion into supporting similar programs within other medical subspecialties is being explored.     

Passive sensitization of human airways induces myogenic contractile responses in vitro

We assessed effects of passive sensitization on human bronchial smooth muscle (BSM) response to mechanical stretching in vitro. Bronchial rings were sham (control) or passively sensitized overnight by using sera from donors demonstrating sensitivity to Dermatophagoides farinae and having immunoglobulin E (IgE) concentrations of 2,600 +/- 200 U/ml. Tissues were fixed isometrically to force transducers to measure responses to electrical field stimulation (EFS) and quick stretch (QS). The myogenic response to QS was normalized to the maximal response to EFS (%EFS). The myogenic response of sensitized BSM was 47.9 +/- 10.9 %EFS to a QS of approximately 6.5% optimal length (Lo); sham-sensitized tissues had a myogenic response of 13.5 +/- 6.4 %EFS (P = 0.012 vs. passively sensitized). A QS of approximately 13% Lo in sensitized BSM caused a response of 82.8 +/- 20.9 %EFS; sham-sensitized tissues developed a response of 38.2 +/- 17.3 %EFS (P = 0.004). BSM incubated with serum from nonallergic donors did not demonstrate increased QS response (4.6 +/- 1.4 %EFS, P = not significant vs. tissue exposed to atopic sera). However, tissues incubated in sera from nonatopic donors supplemented with hapten-specific chimeric IgE (JW8) demonstrated augmented myogenic response to QS of approximately 6.5% Lo (21.9 +/- 6.2 %EFS, P = 0. 027 vs. nonatopic sera alone). We demonstrate that passive sensitization of human BSM preparations causes induction and augmentation of myogenic contractions to QS; this hyperresponsiveness corresponds to the IgE concentration in sensitizing sera.     

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.     

Twin closeness and co-twin risk for substance use disorders: assessing the impact of the equal environment assumption

Studies were conducted from May, 1993 to April, 1995 to determine the changing patterns of infection by the liver fluke, Clonorchis sinensis, among residents and fish hosts in Kyongbuk Province. The infection rate among residents was 7.7% by stool examination. The rate in males (11.3%) was significantly higher than females (4.1%). Positive rate of intradermal test was 27.6% in the same population. The special type of a simple catalytic model was applied for the analysis of intradermal positive reactors by age and sex, and the equation was y = 0.4776 (1 - e-0.0375t) for males and, y = 0.2085 (1 - e-0.0138t) for females. Analysis of stool examination data by two-stage catalytic model revealed y = 0.025 (e-0.00471 - e-0.0235t). The annual Clonorchis infection rate was 4.7 per 1,000 susceptibles and the annual loss rate was 23.5 per 1,000 infected. The frequency distribution by the eggs per gram (EPG) was calculated as well as the cumulative percentages of positives. The regression equations were y = 0.929 + 1.506 log x for males and, y = 0.473 + 1.767 log x for females. Of the 25 fish species, 7 species were infected with Clonorchis metacercariae. Infection rates varied by the species, and ranged from 2.8% in Puntungia herzi to 30.0% in Pseudorasbora parva. Average number of the matacercariae per gram of flesh was 58.1 in P. parva, followed by 10.2 in Gnathopogon atromaculatus, 7.0 in Saurogobio dabryi, and 3.0 in Paracheilognathus rhombea. The present study indicates that clonorchiasis in Kyongbuk Province is less prevalent than that of several decades ago.     

Effect of crosslinking agent content, monomer functionality, and repeat unit chemistry on properties of unfilled resins

Seven mechanical/physical properties were used to evaluate 10 unfilled resins: eight aromatic dimethacrylates and two urethane dimethacrylates. Physical property tests included compressive strength, Young's modulus in compression, uniaxial tensile strength, intrinsic yield point, toothbrush abrasion, Knoop hardness, and water sorption. Controlled changes were made in the following four material parameters: amount of crosslinking diluent present in the uncured monomer, functionality of the monomer, repeat unit chemistry of the monomer (urethane vs. aromatic structure) and mode of activation (chemical vs. visible light). Polymers containing a high concentration of crosslinking agent (50 wt%) were found to be tougher and to possess lower hardness than materials containing lesser amounts of crosslinking agent. This was attributed to the flexible nature of the triethylene glycol dimethacrylate crosslinking molecule. Exposure to water plasticized the highly crosslinked materials to the degree that the yield point and elastic modulus were effectively lowered. Most of the tested properties were unaffected by differences in functionality except resistance to toothbrush abrasion, which was enhanced for polymers derived from high functionality monomers. The urethane-based polymers sorbed substantially more water than the aromatic-based materials, which presumably resulted in lower values for surface hardness. However, the urethane resins were very tough, and excellent resistance to toothbrush abrasion was observed. Property differences caused by differences in activation mode were small, although the visible light materials did sorb more water.