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Biomedical subjects

B Roberts

Publications and source records attributed to B Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Stereologic analysis of monocytes and their subcellular organelles in patients with acute monocytic and myelomonocytic leukemia.

The stereologic characteristics of monocytes from patients with acute nonlymphocytic leukemia containing a monocytic component (FAB M4 and M5), and the monocytes from normal individuals were determined by morphometric analysis. The cells studied were monocytic cells beyond the promonocyte stage of development, as defined by ultrastructural criteria. Parameters evaluated included cell and nuclear volumes and surface areas, mitochondrial and myeloperoxidase (MPO)-positive secretory granule volume and numerical density as well as volume and number of the organelles/cell. Peripheral blood and bone marrow monocytes of leukemic patients could not be distinguished by their cell or organelle stereologic characteristics. Monocytes from patients with both M4 and M5 acute leukemia had relatively large cell and nuclear volumes. Mitochondrial volume density and volume/cell were also high in monocytes from leukemic patients (M4; 21 microns 3/cell, M5 20 microns 3/cell) as compared with monocytes from normal individuals (8.5 microns 3/cell). On the other hand, MPO-positive secretory granule stereologic parameters in monocytes from leukemic patients were indistinguishable from those of normal individuals. A small number (3 of 18) patients showed very low monocyte MPO-positive granule volume densities. There was a slight positive correlation between MPO-positive granule volume density and patient survival time. No relationship between mitochondrial characteristics and survival was noted.

Adult↗
PubMed1989

Antileukemic effects of deferoxamine on human myeloid leukemia cell lines.

Deferoxamine (DFO) possesses antiproliferative activity against mitogen-stimulated lymphocytes, several tumor cell lines, and human leukemia and neuroblastoma cells. We have investigated its effects on the human myeloid leukemia lines HL-60, HEL, and U-937. In suspension culture, DFO causes a dose-dependent inhibition of proliferation of each cell line, with maximal inhibition observed at concentrations greater than 20 microM. These effects were prevented by cotreatment with iron salts and were at least partially reversible by removal of DFO from the culture system or addition of iron before 48 h of DFO exposure. Similar results were obtained in methylcellulose cultures of leukemic cells, with complete abolition of cell aggregates at day 7 in concentrations of 20 microM DFO or higher. DFO treatment caused a dose- and time-related decrease in DNA synthesis as measured by [3H]thymidine uptake, which was also reversed by treatment with iron salts. DFO caused slight reduction in RNA synthesis and did not affect protein synthesis. DFO caused significant antiproliferative effects on three myeloid leukemia cell lines, associated with inhibition of DNA synthesis, with in vitro effects observed at concentrations attainable in vivo. Evaluation of the antileukemic properties of DFO should continue.

Antineoplastic Agents↗
PubMed1989

Experimental evaluation of a synthetic viscoelastic material on intraocular pressure and corneal endothelium.

We compared the effects of 1.0% hyaluronic acid (Healon) and a synthetic viscoelastic polyacrylamide on postoperative intraocular pressure, the corneal endothelium, and various clinical parameters in rabbit and monkey models. Seven rabbit eyes received polyacrylamide and seven received hyaluronic acid during extracapsular cataract extraction with implantation of a polymethylmethacrylate posterior chamber intraocular lens. Intraocular pressure was measured preoperatively, immediately postoperatively, and at 1, 2, 4, 8, 12, and 24 hours postoperatively. Slitlamp examination was performed preoperatively and postoperatively at 3, 7, and 14 days. Axial corneal buttons were taken and scanning electron microscopy of the endothelium was performed. Sections of the globe were studied by light microscopy. Six monkey eyes received polyacrylamide, three received hyaluronic acid, and three received balanced salt solution to reform the anterior chamber after limbal incision with evacuation of aqueous. Intraocular pressure was measured preoperatively, postoperatively, and at 4, 8, 12, 24, and 48 hours postoperatively. Slitlamp examination was performed preoperatively, and at 1, 2, 7, and 14 days postoperatively. Specular endothelial microscopy was performed preoperatively and at 7, 14, and 90 days postoperatively. In the studies performed no significant difference between the eyes receiving polyacrylamide and hyaluronic acid was seen. In the rabbit and monkey models, polyacrylamide is as safe and biocompatible as hyaluronic acid.

Acrylamides↗
PubMed1989

Morphologic and functional alterations in absorptive epithelial cells during L-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum.

L-Tryptophan (L-Trp) has been reported to suppress jejunal fluid and electrolyte transport in vitro, at a 20 mM concentration, whereas other amino acids enhance that absorption at the same concentration. The effect of L-Trp, glycine (Gly) and L-phenylalanine (L-Phe) on in vivo ileal and jejunal fluid and sodium transport, and their morphologic correlates, were investigated in the rat. In the ileum, morphology as well as fluid and sodium transport were more readily altered by L-Trp than in the jejunum. The ileal effects were rapid; morphologic and transport changes were seen within 2.5 minutes. The changes were stereospecific; they occurred only with the levo, but not with the dextro isomer of Trp. There was a concentration dependence; 20 mM levels of L-Trp were required, whereas lower concentrations of the amino acid often stimulated net absorption. Morphologic alterations produced by L-Trp were restricted to absorptive epithelial cells, whereas goblet cells appeared unaffected. Morphologically, L-Trp treatment led to the formation of clear basal vacuoles in ileal absorptive epithelial cells at 2.5 minutes, and extensive vacuolization and loss of the lumenal permeability barrier to macromolecules at 30 minutes. Since L-Trp can be hydroxylated in the small intestine, we assessed the effects of L-5 = OH tryptophan and 5-hydroxytryptamine on small intestinal transport and morphology in this experimental system. L-5-OH tryptophan inhibited fluid transport and produced some epithelial cell vacuolization. However, 5-hydroxytryptamine, which most severely decreased transport, had none of the morphologic effects of L-Trp. We hypothesize that L-Trp may inhibit transport as a result of its intracellular accumulation in absorptive epithelial cells.

Animals↗
PubMed1988

Fine mapping of an H-2Kk restricted cytotoxic T lymphocyte epitope in SV40 T antigen by using in-frame deletion mutants and a synthetic peptide.

The CTL response to SV40 in C3H/HeJ mice is directed against the tumor (T) Ag and is H-2Kk restricted. CTL specific for both the amino terminus (residues 1-271) and the carboxyl terminus (residues 512-708) of the T Ag molecule have been detected, and we have previously cloned CTL of both specificities. In this paper we show that the panel of 10 CTL clones specific for the C-terminal region includes clones specific for three different epitopes, termed C1, C2, and C3. Epitopes C1 and C2 are conserved in the T Ag of the related papova viruses BK and SA12, and only epitopes C2 and C3 are present on SV40 transformed targets bearing the Kk mutant Kkml. Epitopes C1 and C2 were mapped to residues 563-576 by using in-frame deletion mutants of SV40 T antigen, and all clones specific for these two epitopes can lyse Kk bearing target cells in the presence of a synthetic peptide comprising residues 559-576. Kk and Kkml differ at residue 152, which is located in the Ag-binding pocket. Because epitopes C1 and C2 can be formed by the same antigenic peptide, but epitope C1 is not present on SV40 transformed Kkml cells, epitopes C1 and C2 must differ in the contribution made by residue 152 of the MHC class I molecule. These data show that CTL epitopes on transformed cells can be made up of Ag fragments, and strengthen the idea that this is a general phenomenon for both class I and class II restricted T cell epitopes.

Amino Acid Sequence↗
PubMed1988

Cystathionine metabolism in neuroblastoma.

Cystathioninuria is a frequent and highly specific marker of neuroblastoma, but the etiology of this abnormality has not been well studied. To investigate this phenomenon, we analyzed 27 human neuroblastoma tissue specimens for the presence of cystathionine synthase and cystathionase. Levels of cystathionine synthase varied from undetectable to 622 pmol/mg protein, but no specimen had cystathionase measurable by rocket radioimmunoassay or catalytic assay. In addition, we assayed neuroblastoma cell lines exposed to a variety of differentiating agents: butyric acid, dimethyl sulfoxide, serum-free medium, or sodium citrate to induce differentiation. In each case we were unable to demonstrate cystathionase induction. These data are consistent with the hypothesis that neuroblastomas have a biochemical block in the transsulfuration enzymes at the level of cystathionase and that expression of cystathionine synthase in the absence of cystathionase may account for the presence of cystathioninuria in patients with neuroblastoma.

Cell Differentiation↗
PubMed1988

Non-Hodgkin's lymphoma: case control epidemiological study in Yorkshire.

This paper reports the results of a case control study of non-Hodgkin's lymphoma in the Yorkshire Health Region. In all, 437 cases and 724 controls were interviewed. Risk factors associated with past skin conditions, family history of cancer and infectious mononucleosis, aspects of social life and contact with wood dust and epoxy glues all emerge. A comparison of high and low grade morphological forms of disease reveal contrasting risks and suggest separate aetiologies for these conditions.

England↗
PubMed1988

The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen.

The carboxy-terminal tail of nucleoplasmin, which specifies entry into the cell nucleus, contains four short sequences that are similar to previously identified nuclear location sequences. We show that none of these is able to locate chicken muscle pyruvate kinase to the cell nucleus. Deletion analysis was used to determine the limits of a nuclear location sequence and indicated that a 14-amino acid segment (RPAATKKAGQAKKK) should function as a minimal nuclear location sequence. When tested directly, however, this sequence was unable to locate pyruvate kinase to the cell nucleus. Restoration of three amino acids of nucleoplasmin sequence at either end of this sequence generated sequences that were able to locate pyruvate kinase to the cell nucleus. The 14-amino acid proposed minimal nuclear location sequence is present in the functional sequences, AVKRPAATKKAGQAKKK, RPAATKKAGQAKKKKLD, and the sequence AVKRPAATKKAGQAKKKKLD, which has additional amino acids at both ends. The minimal sequence element is therefore necessary but not sufficient for transport into the cell nucleus. This unusual feature of the nucleoplasmin nuclear location sequence suggests ways in which it could interact with the nuclear transport mechanism.

Amino Acid Sequence↗