Heparin for oral use: preliminary studies.
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Administration, Oral↗
Biomedical subjects
B Roberts
Publications and source records attributed to B Roberts.
Cloning of the goat beta-casein-encoding gene and expression in transgenic mice.
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.
Amino Acid Sequence↗
Seroprevalence of HTLV-1 and HTLV-2 among intravenous drug users and persons in clinics for sexually transmitted diseases.
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.
Adult↗
Comparative biological responses of rabbits infected with human T-lymphotropic virus type I isolates from patients with lymphoproliferative and neurodegenerative disease.
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.
Animals↗
Low risk of mother-to-child transmission of human T lymphotropic virus type II in non-breast-fed infants. The NYC Perinatal HIV Transmission Collaborative Study.
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.
Adult↗
The personality of young adult couples and wives' work patterns.
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.
Adult↗
Portable light for ophthalmic surgery in the tropics.
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Developing Countries↗
Infectious transmission of human T-cell lymphotropic virus type II in rabbits.
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.
Animals↗
Immunohistochemical localization, purification, and characterization of human urinary bladder glutathione S-transferases.
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.
Adult↗
HTLV-II endemicity among Guaymi Indians in Panama.
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HTLV-II Infections↗
A surgical approach to vascular disease.
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Angiography↗
Reversal of benzodiazepine sedation with the antagonist flumazenil.
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.
Adolescent↗
Human T lymphotropic virus type II (HTLV-II) infection in a cohort of New York intravenous drug users: an old infection?
To identify risk factors for human T lymphotropic virus type II (HTLV-II) infection in intravenous drug users (IVDUs), participants in a longitudinal study of human immunodeficiency virus (HIV) infection in a New York methadone maintenance program were studied. Of 270 participants tested for HTLV-I/II, 21 (8%) were seropositive. Of those, 15 (71%) had HTLV-II-specific sequences by polymerase chain reaction (PCR) and 1 (5%) had both HTLV-I- and -II-specific sequences; 3 persons with indeterminate serologic results were also PCR-positive for HTLV-II. HTLV-II infection was significantly associated with older age but was not predicted by sex, race, socioeconomic status, transfusion history, or HIV infection status. Behavioral factors since 1978, such as duration and frequency of intravenous drug use, needle sharing, visits to shooting galleries, or number of sex partners, were also not associated with HTLV-II infection. These findings are in contrast with the association of these risk factors with HIV in this group and suggest that, among IVDUs, HTLV-II is an older endemic infection that is less efficiently transmitted than HIV.
Adult↗
HTLV-I-associated myelopathy/tropical spastic paraparesis in the United States.
HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is endemic in the Caribbean basin and Japan. Because of the close proximity of the United States to the Caribbean and the presence of HTLV-I-seropositive persons in the United States, we sought reports of patients who were HTLV-I seropositive and had a slowly progressive myelopathy. Over a 2-year period, there were 25 patients reported, 19 of whom were black and 12 of whom had been born in the United States. All patients except two had become symptomatic while living in the United States. Six patients had no apparent risk factor for acquiring HTLV-I. These data demonstrate that HAM/TSP is occurring in the United States and that the diagnosis of HAM/TSP should be considered in patients with a slowly progressive myelopathy regardless of risk factors for acquiring HTLV-I.
Adult↗
Differential expression of glutathione S-transferase, glutathione peroxidase and glutathione reductase in normal and malignant human breast tissues.
In the present study we have compared the levels of glutathione (GSH) S-transferase, GSH peroxidase and GSH reductase in human breast tumors and adjacent normal tissues obtained from the same individuals. We have also quantitated GST pi type antigen in these samples by western blotting. GST pi activity towards 1-chloro-2,4-dinitrobenzene was found to be elevated in tumors from three out of six patients (patient nos. 2, 4 and 5), whereas this activity was suppressed in tumor from patient no. 1. Results of Western blotting using antibodies raised against GST pi of human placenta were in agreement with the GST activity data. GSH peroxidase activity with cumene hydroperoxide as substrate was found to be elevated in four tumor samples (patient nos. 2, 4, 5, and 6) but suppressed in tumor from patient no. 1. On the other hand, GSH reductase activity was elevated in three samples (patients nos. 2, 4 and 5) and downregulated in the remaining three samples (patients nos. 1, 3 and 6). These results indicate that GSH-related enzymes are differentially altered in human breast tumors and GST pi type isoenzyme(s), unlike certain other human carcinomas such as colonic, are not uniformly elevated in human breast tumors.
Adult↗
In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment.
Chimeric chloramphenicol acetyltransferase and beta-galactosidase marker genes were coated onto fine gold particles and used to bombard a variety of mammalian tissues and cells. Transient expression of the genes was obtained in liver, skin, and muscle tissues of rat and mouse bombarded in vivo. Similar results were obtained with freshly isolated ductal segments of rat and human mammary glands and primary cultures derived from these explants. Gene transfer and transient expression were also observed in eight human cell culture lines, including cells of epithelial, endothelial, fibroblast, and lymphocyte origin. Using CHO and MCF-7 cell cultures as models, we obtained stable gene transfer at frequencies of 1.7 x 10(-3) and 6 x 10(-4), respectively. The particle bombardment technology thus provides a useful means to transfer foreign genes into a variety of mammalian somatic cell systems. The method is applicable to tissues in vivo as well as to isolated cells in culture and has proven effective with all cell or tissue types tested thus far. This technology may therefore prove to be applicable in various aspects of gene therapy.
Animals↗
The influence of extraneous sounds on the perceptual estimation of first-formant frequency in vowels.
The contribution of extraneous sounds to the perceptual estimation of the first-formant (F1) frequency of voiced vowels was investigated using a continuum of vowels perceived as changing from/I/to/epsilon/as F1 was increased. Any phonetic effects of adding extraneous sounds were measured as a change in the position of the phoneme boundary on the continuum. Experiments 1-5 demonstrated that a pair of extraneous tones, mistuned from harmonic values of the fundamental frequency of the vowel, could influence perceived vowel quality when added in the F1 region. Perceived F1 frequency was lowered when the tones were added on the lower skirt of F1, and raised when they were added on the upper skirt. Experiments 6 and 7 demonstrated that adding a narrow-band noise in the F1 region could produce a similar pattern of boundary shifts, despite the differences in temporal properties and timbre between a noise band and a voiced vowel. The data are interpreted using the concept of the harmonic sieve [Duifhuis et al., J. Acoust. Soc. Am. 71, 1568-1580 (1982)]. The results imply a partial failure of the harmonic sieve to exclude extraneous sounds from the perceptual estimation of F1 frequency. Implications for the nature of the hypothetical harmonic sieve are discussed.
Adult↗
Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption: effect of early weaning to artificial diets.
We studied the effect of early weaning from maternal breast milk to artificial diets on rat jejunal absorption of an exogenous 40-kD glycoprotein, horseradish peroxidase (HRP). Rat pups, fed maternal milk (MM) from birth, received one of three diets for the last 4 d before weaning (d 17-21): MM, protein hydrolysate formula (PH), or soy formula (S). Some rats were pretreated on d 14 with intraperitoneal hydrocortisone (5 mg/rat). In MM-fed rat pups, jejunal HRP absorption was markedly higher on d 17 than on d 21. [Geometric means (95% confidence interval) were: d 17, 626.4 (461.3, 850.6) versus d 21, 90.6 (48.2, 170.5) IU HRP/mL x cm x min, p less than 0.01.] By contrast, 21-d-old PH- and S-fed pups maintained elevated absorption of the tracer [PH, 292.3 (177.5, 480.6), p less than 0.05 versus MM pups, S, 340.8 (164.4, 704.8), p less than 0.01 versus MM pups]. Wt-matched control studies indicate that the difference in HRP absorption was not due to the smaller body wt of formula-fed pups. The increased absorption in formula-fed animals was suppressed by hydrocortisone. In S-fed pups, the increased macromolecular absorption appeared, in part, to be the result of diffusion across altered villus absorptive cells. In PH-fed pups, there was no evidence of damage and HRP absorption appeared to occur by vesicle-mediated transport. Delay in the normal maturation of small intestinal "closure" appears to be associated with early weaning to artificial diets. This may lead to increased nonspecific macromolecular permeability that could result in immune-mediated sensitization and food intolerance.
Age Factors↗