Child resistant containers for liquid medications.
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Biomedical subjects
Publications and source records attributed to B Roberts.
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Recent evidence indicates that higher dipterans biosynthesize predominantly the novel juvenile hormone (JH) bisepoxide, methyl (2E,6trans)-6,7,10,11-bisepoxy-3,7,11-trimethyl-2-dodecen oate (JHB3), together with a small proportion of methyl (2E,6E)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate (JHIII) and possibly its 6,7-epoxy isomer. A strategy of gas chromatography-mass spectrometry (GC-MS) involving cool on-column GC and negative-ion chemical ionization MS has enabled the selective analysis of underivatized JH-like products released in vitro by ring glands and corpora allata of Lucilia cuprina. JHB3 is released to the exclusion of mono-epoxidized and unepoxidized esters. The rate of JHB3 release in adult females increases dramatically after protein feeding from 0.2 to 5.2 pmol/h/gland. Values agree well with the rate of JH biosynthesis determined by radiochemical assay. As revealed by thin-layer chromatography, the radiolabel is predominantly incorporated into JHB3, of which only 2% is retained in the corpus allatum indicating almost immediate release from the gland. Approximately 5% of radioactive material retained in the glands co-migrates with JHIII and may be an intermediate in JHB3 synthesis. We conclude that JHB3 is the only juvenile hormone biosynthesized in vitro by L. cuprina. The data suggest that JHB3 may be the exclusive JH synthesized by higher dipterans.
A human T cell lineage was used to determine the possible effects of HIV infection on T cell antioxidant status. On inoculation into serum-free culture, 8E5, a constitutive HIV-expressing T cell line, underwent apoptosis whereas cell death was not observed with the uninfected A3.01 or latently HIV-infected 8E5L T cell lines. 8E5 survival was markedly prolonged by supplementing the serum-free medium with either A3.01-conditioned medium, catalase, vitamin E, or 2-mercaptoethanol, but supplementation with ascorbic acid, glutathione, or N-acetylcysteine had no effect. Consistent with their being in a state of oxidative stress, 8E5 cells displayed reduced levels of catalase activity, and were more susceptible to killing by exogenous hydrogen peroxide (H2O2) than A3.01 and 8E5L cells. These results demonstrate an inverse correlation between HIV gene expression and antioxidant status in human T cells. Enhanced cytotoxicity of HIV-infected, antioxidant-deficient CD4 T cells following exposure to H2O2 in lymphoid tissues responding to opportunistic pathogens may contribute to the depletion of CD4 T cells in AIDS.
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A single even-numbered harmonic can be segregated from an odd-harmonic complex more easily than its odd-numbered neighbors, for low fundamentals [Roberts and Bregman, J.Acoust. Soc. Am. 90, 3050-3060 (1991)]. It has been proposed that this effect occurs because the even harmonic is inconsistent with the regular spectral pattern formed by the odd harmonics. However, in this study we evaluate some alternative accounts of the effect. The stimuli were harmonic complex tones for which one of the components was cued by a preceding pure tone. Subjects were required to listen for the cued component and either to rate its clarity (experiments 1 and 3) or to judge its pitch in relation to the preceding tone (experiment 2). It is argued that the weaker fusion of an added even harmonic depends on its status as an added component rather than as an even harmonic (experiment 1), and on its immediate perceptual salience rather than on auditory learning. An even-odd difference was also found when even and odd harmonics were tested in an identical spectral context (experiment 2), and when one of the neighboring odd harmonics was removed (experiment 3). These results are consistent with the proposal that it is easier to segregate a harmonic from a periodic complex tone when it does not form part of the regular pattern of spectral spacing defined by the other harmonics.
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The goat beta-casein-encoding gene (CSN2), which encodes the most abundant protein of goat milk, has been cloned and sequenced. The intron/exon organization of the 9.0-kb goat CSN2 gene is similar to that of other CSN2 genes. Expression of the goat gene was principally restricted to the mammary gland of lactating transgenic animals. A low level of expression was also observed in skeletal muscle and skin. In contrast to a rat CSN2 transgene [Lee et al., Nucleic Acids Res. 16 (1988) 1027-1041], the goat gene was expressed to a high degree in the lactating mammary gland. Differences in the content or context of regulatory elements may account for the enhanced performance of the goat relative to the rat CSN2 gene in transgenic mice.
UNLABELLED: Background. The human T-cell lymphotropic virus Type I (HTLV-I) is associated with adult T-cell leukemia and myelopathy, whereas HTLV-II infection has uncertain clinical consequences. We assessed the seroprevalence of these retroviruses among intravenous drug users and among patients seen at clinics for sexually transmitted diseases (STD clinics). METHODS: We used serum samples that were collected in eight cities in 1988 and 1989 during surveys of human immunodeficiency virus infection among intravenous drug users entering treatment and persons seen in STD clinics. The serum samples were tested for antibodies to HTLV, and positive specimens were tested further by a synthetic peptide-based enzyme-linked immunosorbent assay to differentiate between HTLV-I and HTLV-II. RESULTS: Among 3217 intravenous drug users in 29-drug-treatment centers, the median seroprevalence rates of HTLV varied widely according to city (range, 0.4 percent in Atlanta to 17.6 percent in Los Angeles). Seroprevalence increased sharply with age, to 32 percent in persons over 44 years of age. HTLV infection was more common among blacks (15.5 percent) and Hispanics (10.7 percent) than among whites (4.1 percent), and it was strongly associated with a history of heroin injection (P less than or equal to 0.001). Among 5264 patients in 24 STD clinics, the median rates of HTLV infection were much lower (range, 0.1 percent in Atlanta and Newark to 2.0 percent in Los Angeles). Again, this infection was more common among intravenous drug users (7.6 percent) than among non-drug users (0.7 percent). Eighty-four percent of the seropositive samples from drug-treatment centers and 69 percent of those from STD clinics were due to HTLV-II infection (P = 0.03). CONCLUSIONS: HTLV infections are common among intravenous drug users and are primarily caused by HTLV-II. Among patients seen at STD clinics, HTLV is strongly associated with intravenous drug use, but the retrovirus is also prevalent among non-drug users.
An experimental rabbit model was used to determine host responses to infection by various human T-lymphotropic virus type-I (HTLV-I) strains. Seven groups of 4 to 5 rabbits each were inoculated with lethally-irradiated HTLV-I-infected cell lines derived from patients with adult T-cell leukemia/lymphoma or from patients with HTLV-I-associated myelopathy. Four separate control groups of 2 rabbits each were inoculated with similarly prepared HTLV-I-negative cells derived from rabbits or humans. Anti-viral antibody responses were assessed by immunoblot assay and hematologic parameters were measured using automated cell counters and cytologic staining. The virologic status of challenged rabbits was determined by co-culture and HTLV-I antigen capture assay, as well as by polymerase chain reaction (PCR) amplification of HTLV-I DNA from peripheral blood mononuclear cells (PBMC) or tissues. The HTLV-I inocula could be separated into groups based upon their infectivity to rabbits: highly infectious strains elicited intense serologic responses and were detected frequently in tissues by antigen and PCR assays, while other strains were moderately to poorly infectious, induced weak antibody responses and were infrequently detected by antigen and PCR assays. Overall, PBMC appeared to have the greatest quantity of HTLV-I containing cells, while bone marrow was a poor source of virus. No clinical or hematologic abnormalities were evident during the 24-week course of infection. Taken together, our results suggest there is heterogeneity in the biological response to HTLV-I infection which is, in part, dependent on the infecting strain of virus.
The transmissibility of human T lymphotropic virus (HTLV) type II from mother to child was investigated. Of 236 women enrolled during pregnancy in a study of mother-to-child transmission of human immunodeficiency virus in 1986-1988, 21 (8.9%) were seropositive for HTLV-I/II. All 21 mothers were infected with HTLV-II by synthetic peptide testing and polymerase chain reaction (PCR). HTLV-II-infected women were older (median age, 34 vs. 28 years), more likely to be black (70% vs. 38%), and more likely to report past or current intravenous drug use (85% vs. 56%) than HTLV-II-uninfected women. Of 20 non-breast-fed infants born to 19 of these HTLV-II-infected women, none had detectable HTLV-II by PCR done on peripheral blood mononuclear cells obtained at birth to 36 months of age. Serologic testing of these infants revealed gradual disappearance of HTLV-I/II antibody. While this study does not rule out the possibility of perinatal HTLV-II transmission, the data suggest that it occurs rarely in the absence of breast-feeding.
The influence of personality in 63 couples at the time of family formation on wives' work patterns 15 years later was examined in variable-centered and person/couple-centered ways. Four factor dimensions on the Adjective Check List assessed personality. Work patterns were assessed with measures of type, amount, and status of work and with schematic work narratives describing characters and plots abstracted from wives' mid-life data. Hierarchical regression analyses showed individuality of husbands to affect work outcomes after wives' college-age goals, their young adult personality, and the duration of marriages were taken into account. Conjoint high-low patterns of individuality in 34 couples were associated with different schematic work stories. These stories show distinctive personality and relational correlates at age 27. They flesh out and qualify hypotheses that individualistic partners would be open to women's careers and would show revealing strategies of combining self- and other interests in the transition to parenthood.
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To determine the susceptibility of rabbits to experimental infection with human T-cell lymphotropic virus type-II (HTLV-II), four separate groups of four weanling rabbits each were inoculated intravenously with lethally irradiated HTLV-II-infected human cell lines Mo-T (HTLV-IIMo-infected T cells), WIL-NRA (an Epstein-Barr virus [EBV]-transformed B-lymphoblastoid cell line infected with HTLV-IINRA), 729pH6neo (an EBV-transformed lymphoblastoid cell line transfected with a molecular clone of HTLV-IIMo), or G12.1 (HTLV-II-infected T cells from a Panamanian Guaymi Indian). Two additional groups of four rabbits each were similarly inoculated with control uninfected 729 or HuT 78 cells. Early and persistent seroconversion to HTLV-II core antigen p24, as determined by Western immunoblot, occurred in all HTLV-II-inoculated rabbits and was most intense in rabbits inoculated with G12.1 cells; seroreactivity to other HTLV-II gag or env antigens occurred later, with less intensity, or not in all inoculated rabbits. Peripheral blood mononuclear cells (PBMC) and other lymphoid cells from HTLV-II-inoculated rabbits produced minimal p24 in vitro, as determined by enzyme immunosorbent capture assay. Virus was more readily detected by polymerase chain reaction amplification of HTLV-II pol sequences; this occurred most frequently in rabbits inoculated with Mo-T cells, and most frequently in PBMC as compared with other tissues tested (bone marrow, brain, and liver). No evidence of disease occurred in HTLV-II-inoculated rabbits observed for as long as 24 weeks. All control rabbits remained negative for evidence of HTLV-II infection, as determined by the same procedures. These results provide the first evidence of HTLV-II infection in a species other than humans, and demonstrate the usefulness of the rabbit as an animal model to study the biologic response to different isolates of this human retrovirus.
This study describes immunohistochemical localization, purification and characterization of glutathione S-transferase (GST) of human urinary bladder. Even though all the three major classes of isoenzymes (alpha, mu, and pi) were expressed in human bladder, more than 90% of total GST activity was accounted for by a pi class anionic form. Human bladder alpha, mu, and pi class GSTs were immunologically related to respective isoenzymes of other human tissues. GST pi was present in all 13 samples analyzed, whereas GST alpha and mu were detected in nine and eleven samples, respectively. GST alpha of human bladder appeared to be unique, because unlike this class of GSTs of other human tissues, bladder enzyme had lower affinity for GSH linked to epoxy-activated Sepharose 6B affinity resin. Immunohistochemical staining indicated localization of GST alpha in epithelial surface cells, underlying submucosa and smooth muscle, whereas mu and pi class isoenzymes were predominantly distributed in epithelial surface cells. These results suggest that human bladder GSTs may play an important role in providing protection against xenobiotics because epithelium is considered a target for several carcinogens and all the three classes of isoenzymes are expressed in these cells.
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The effectiveness of the benzodiazepine antagonist, flumazenil, was evaluated in a randomized double-blind clinical study in which diazepam 0.2 mg kg-1 or midazolam 0.1 mg kg-1 was used for i.v. sedation. We studied 120 day-case patients undergoing gastroscopy and treated with either flumazenil 0.1-2 mg or placebo after the procedure. Psychometric assessment of four aspects of recovery over a 3-h period showed that flumazenil attenuated the sedative effects of the benzodiazepines, but did not antagonize the sedation completely. For patients sedated with diazepam, there was a significant effect of flumazenil on speed of motor co-ordination after 90 min (P less than 0.01), and for those given midazolam a similar effect was found at 20 min (P less than 0.01). However, after 3 h all four groups of patients had not returned to baseline performance in accuracy of motor co-ordination (P less than 0.01) and cortical arousal (P less than 0.05), and the two groups sedated with diazepam still displayed memory deficits (P less than 0.05). Flumazenil did not attenuate the subjective experience of sedation as measured by visual analogue scales. These results indicate that sedation is multidimensional, differentially affecting the hierarchy of cognitive functions. In day-cases, antagonism of benzodiazepine sedation with flumazenil would not hasten the safe discharge of patients.