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Biomedical subjects

R Lee

Publications and source records attributed to R Lee.

At least 127 records · Page 7Linked to original sources
PubMed1999

Endurance training of the trunk extensor muscles in people with subacute low back pain.

BACKGROUND AND PURPOSE: Clinicians treating patients with low back pain often use exercise to reduce pain and improve function. The aim of this study was to evaluate the effectiveness of trunk extensor endurance training in reducing pain and decreasing disability in subjects with subacute low back pain (ie, onset of back pain within 7 days to 7 weeks). SUBJECTS AND METHODS: Patients were randomly assigned to either an experimental group or a control group. A visual analog scale and the pain rating index (PRI) of the McGill Pain Questionnaire (MPQ) were used to obtain baseline measurements of pain. The Roland Morris Disability Questionnaire (RMDQ) was used to measure disability, and the Sorensen Test was used to measure trunk extensor endurance. Subjects in the experimental group attended exercise sessions 3 times a week for 6 weeks. Subjects in the control group did not do exercises. Both groups were given back care advice and hot packs for 15 minutes, 3 to 5 times per week. Reassessments were carried out at 3 and 6 weeks. RESULTS: There were differences between the 2 groups at 3 weeks in regard to pain intensity during the evaluation session and pain experienced over the preceding 24 hours, the total MPQ PRI, the sensory component of the MPQ PRI, and the RMDQ. At 6 weeks, no differences were found for pain measurements, disability scores, and holding time on the Sorensen Test. CONCLUSION AND DISCUSSION: Trunk extensor endurance training reduced pain and improved function at 3 weeks but resulted in no improvement at 6 weeks when compared with the control group. Endurance exercise is considered to expedite the recovery process for patients with an acute episode of low back pain.

Adult↗
PubMed1998

Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene.

Albright hereditary osteodystrophy (AHO), an autosomal dominant disorder characterized by short stature, obesity, and skeletal defects, is associated with heterozygous inactivating mutations of GNAS1, the gene encoding the heterotrimeric G protein alpha-subunit (Gsalpha) that couples multiple receptors to the stimulation of adenylyl cyclase. It has remained unclear why only some AHO patients present with multihormone resistance and why AHO patients demonstrate resistance to some hormones [e.g., parathyroid hormone (PTH)] but not to others (e.g., vasopressin), even though all activate adenylyl cyclase. We generated mice with a null allele of the mouse homolog Gnas. Homozygous Gs deficiency is embryonically lethal. Heterozygotes with maternal (m-/+) and paternal (+/p-) inheritance of the Gnas null allele have distinct phenotypes, suggesting that Gnas is an imprinted gene. PTH resistance is present in m-/+, but not +/p-, mice. Gsalpha expression in the renal cortex (the site of PTH action) is markedly reduced in m-/+ but not in +/p- mice, demonstrating that the Gnas paternal allele is imprinted in this tissue. Gnas is also imprinted in brown and white adipose tissue. The maximal physiological response to vasopressin (urinary concentrating ability) is normal in both m-/+ and +/p- mice and Gnas is not imprinted in the renal inner medulla (the site of vasopressin action). Tissue-specific imprinting of Gnas is likely the mechanism for variable and tissue-specific hormone resistance in these mice and a similar mechanism might explain the variable phenotype in AHO.

Alleles↗
PubMed1998

The p51 subunit of human immunodeficiency virus type 1 reverse transcriptase is essential in loading the p66 subunit on the template primer.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a dimeric enzyme consisting of p66 and p51 subunits. The functional role of the p51 subunit remains elusive since all the catalytic functions appear to be executed through the p66 subunit. We report here that the p51 subunit, in addition to providing structural support to the p66 subunit, may be involved in facilitating the loading of the p66 subunit on to the template-primer (TP). This possibility is supported by following observations: (i) Upon binding to the TP, the p51 subunit can be dissociated by acetonitrile treatment and the template-primer-bound p66 monomer alone is capable of catalyzing DNA synthesis. (ii) Photo-cross-linking of template-primer to HIV-1 RT is abolished by dissociation of the p51 subunit prior to the TP binding but remains unaffected after the TP binding step. (iii) The p66-TP covalent complex selectively generated by UV irradiation and separated by gel electrophoresis can incorporate a single nucleotide in situ upon its renaturation in the gel. (iv) Treatment of HIV-1 RT with (tert-butyldimethylsilyl)spiroaminooxathioledioside (TSAO), an inhibitor that specifically binds to the beta7 beta8 loop of p51, destabilizes the heterodimeric enzyme, resulting in the subsequent loss of DNA binding.

Acetonitriles↗
PubMed1998

Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin.

The Ikaros gene encodes multiple protein isoforms that contribute critical functions during the development of lymphocytes and other hematopoietic cell types. The intracellular functions of Ikaros are not known, although recent studies have shown that Ikaros proteins colocalize with inactive genes and centromeric heterochromatin. In this study, Ikaros proteins were found to be components of highly stable complexes. The complexes from an immature T cell line were purified, revealing associated proteins of 70 and 30 kD. The p70 gene, named Helios, encodes two protein isoforms with zinc finger domains exhibiting considerable homology to those within Ikaros proteins. Helios and Ikaros recognize similar DNA sequences and, when overexpressed, Helios associates indiscriminately with the various Ikaros isoforms. Although Ikaros is present in most hematopoietic cells, Helios was found primarily in T cells. The relevance of the Ikaros-Helios interaction in T cells is supported by the quantitative association of Helios with a fraction of the Ikaros. Interestingly, the Ikaros-Helios complexes localize to the centromeric regions of T cell nuclei, similar to the Ikaros localization previously observed in B cells. Unlike the B cell results, however, only a fraction of the Ikaros, presumably the fraction associated with Helios, exhibited centromeric localization in T cells. These results establish immunoaffinity chromatography as a useful method for identifying Ikaros partners and suggest that Helios is a limiting regulatory subunit for Ikaros within centromeric heterochromatin.

Amino Acid Sequence↗
PubMed1998

Summary of workshop findings for antibodies reacting with porcine T-cells and activation antigens: results from the Second International Swine CD Workshop.

After initial evaluation of the 176 new and 19 control monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, 57 were assigned to the T-cell/activation marker subgroup. These 57 mAb were further analyzed using flow cytometry on whole blood lymphocytes, splenocytes, Peyer's patch lymphocytes, in vitro cell lines, broncho-alveolar lavage cells, Con A and PHA blasts, fetal cell populations, and by 2-color flow cytometry against mAb to porcine CD2, CD4, and CD8. Finally, the molecular weights of the target antigens were characterized when possible. As a result of these analyses, 23 mAb were distributed into 7 CD clusters. Newly confirmed mAb assignments included: two CD2; one CD4; two CD5; one wCD6; and one wCD25. Three new mAb were found that reacted with wCD8, one of which defined a new epitope, wCD8c. For the first time, mAb against porcine CD3 were identified, including 6 mAb that reacted with three different epitopes. Several new mAb reacted with antigens whose expression varied depending on the activation state of the test cell. These will require further characterization in order to assign a CD number.

Animals↗
PubMed1998

Analyses of monoclonal antibodies reacting with porcine CD3: results from the Second International Swine CD Workshop.

Among the 57 monoclonal antibodies (mAb) analyzed within the T-cell group from the Second Swine CD Workshop, six mAb fell within clusters T10 and T11 (No. 088, STH164; No. 148, FY1A3; No. 149, FY2C1; No. 150, FY1H2; No. 151, FY2A11; No. 169, BB23-8E6). The mAb within these two groups gave a similar appearance on flow cytometry and stained all peripheral blood T-cells as defined by CD4 and wCD8 staining. All six mAb precipitated a 24 kDa protein. On the basis of inhibition analyses performed as part of the workshop and from published data, the mAb define at least three epitopes. There is only minimal stimulation of resting peripheral lymphocytes, but four of the mAb produce strong stimulation in the presence of PMA. With the exception of STH164, all have been shown to react with CD3 epsilon-transfected COS cells. The new mAb, therefore, react with three epitopes on porcine CD3 epsilon designated CD3a (BB23-8E6, FY2A11), CD3b (FY1A3, FY2C1), and CD3c (FY1H2). mAb STH164 appears to be reactive with another epitope, however, since its reactivity with CD3 has not been confirmed it is designated as wCD3.

Animals↗
PubMed1998

Analyses of monoclonal antibodies reacting with porcine CD5: results from the Second International Swine CD Workshop.

Among the 57 monoclonal antibodies analyzed within the T-cell group, three mAbs fell within cluster T13 including the CD5a standard b53b7 (No. 174). The two new mAbs 1H6/8 (No. 058) and BB6-9G12 (No. 166) both precipitated 55 and 60 kDa proteins that were of similar molecular weights as the standard. Staining patterns on the various cell types were similar. Both new antibodies inhibited the binding of the CD5a reference mAbs b53b7 to peripheral lymphocytes. These mAbs, therefore both react with the CD5a epitope bringing the number of anti-porcine CD5 mAbs to eight, all of which appear to recognize the same epitope.

Animals↗
PubMed1998

Analyses of monoclonal antibodies reacting with porcine wCD6: results from the Second International Swine CD Workshop.

Among the 57 monoclonal antibodies analyzed within the T-cell group of the Second International Swine CD Workshop, one mAb fell within cluster T14a that included the CD6 standard a38b2 (No. 175). The new mAb MIL8 (No. 082) and a38b2 both precipitated from activated T-cells a 150 kDa monomeric protein. Staining patterns on the various cell types were similar. There was no inhibition of binding of either mAb to peripheral blood T-cells with the opposite mAb. The new mAb, MIL8, reacts with a separate epitope on porcine wCD6.

Animals↗
PubMed1998

Report on the analyses of mAb reactive with porcine CD8 for the second international swine CD workshop.

Based on an analysis of their reactivity with porcine peripheral blood lymphocytes (PBL), only three of the 57 mAbs assigned to the T cell/activation marker group were grouped into cluster T9 along with the two wCD8 workshop standard mAbs 76-2-11 (CD8a) and 11/295/33 (CD8b). Their placement was verified through the use of two-color cytofluorometry which established that all three mAbs (STH101, #090; UCP1H12-2, #139; and PG164A, #051) bind exclusively to CD8+ cells. Moreover, like the CD8 standard mAbs, these three mAbs reacted with two proteins with a MW of 33 and 35 kDa from lymphocyte lysates and were, thus, given the wCD8 designation. Because the mAb STH101 inhibited the binding of mAb 76-2-11 but not of 11/295/33, it was given the wCD8a designation. The reactivity of the other two new mAbs in the T9 cluster with the various subsets of CD8+ lymphocytes were distinct from that of the other members in this cluster including the standards. Although the characteristic porcine CD8 staining pattern consisting of CD8low and CD8high cells was obtained with the mAb UCP1H12-2, a wider gap between the fluorescence intensity of the CD8low and CD8high lymphocytes was observed. In contrast, the mAb PG164A, not only exclusively reacted with CD4-/CD8high lymphocytes, but it also failed to recognize CD4/CD8 double positive lymphocytes. It was concluded that this mAb is specific for a previously unrecognized CD8 epitope, and was, thus, given the wCD8c designation. A very similar reactivity pattern to that of PG164A was observed for two other mAbs (STH106, #094; and SwNL554.1, #009). Although these two mAbs were not originally positioned in the T cell subgroup because of their reactivity and their ability to inhibit the binding of PG164A, they were given the wCD8c designation. Overall, five new wCD8 mAbs were identified. Although the molecular basis for the differences in PBL recognition by these mAbs is not yet understood, they will be important in defining the role of CD8+ lymphocyte subsets in health and disease.

Animals↗
PubMed1998

Polyamide nucleic acid targeted to the primer binding site of the HIV-1 RNA genome blocks in vitro HIV-1 reverse transcription.

We report here that polyamide nucleic acid (PNA) as well as a polyamide nucleic acid-DNA chimera complementary to the primer binding site of the HIV-1 genome can completely block priming by tRNA3Lys and consequently the in vitro initiation of reverse transcription by HIV-1 RT. Conventional heating and cooling is not required for annealing PNA analogs to the complementary nucleotide sequence as effective blockage of reverse transcription results from their invasion in the duplex region of preprimed U5-PBS HIV-1 RNA template-primer and was seen even at ambient temperature. Further, the extension of the initiated nascent (-) strand DNA can also be blocked by inclusion of another PNA, targeted to upstream sequences in the U5 region of the viral RNA. Interestingly, a PNA chimera having only two DNA nucleotides annealed with the U5-PBS RNA is recognized as a bonafide primer by HIV-1 RT, as the 3'OH end of the chimeric molecule is extended by the enzyme in the presence of dNTPs. A significant observation was that RNA/PNA or RNA/(PNA-DNA) hybrids were entirely resistant to the RNase H activity of HIV-1 RT. Furthermore, PNA invasion into the RNA/DNA hybrid completely prevented the cleavage of the RNA strand, suggesting that the RNase H activity of HIV-1 RT which was required in reverse transcription may also be inhibited by the PNA oligomer. These observations suggest that oligomeric PNAs targeted to various critical regions of the viral genome are likely to have strong therapeutic potential for interrupting multiple steps involved in the replication of HIV-1 and warrant serious investigation especially in the area of an effective delivery system.

Anti-HIV Agents↗
PubMed1998

The influence of hepatitis C virus genotypes on the outcome of liver transplantation.

BACKGROUND: The aim of this study was to report the influence of hepatitis C virus (HCV) genotypes and HLA matches on the outcome of liver transplantation, hepatitis recurrence, and progression to cirrhosis after transplantation. METHODS: HCV genotypes were determined from pretransplantation sera and/or liver explant tissues from 202 patients with HCV-related end-stage liver disease. One hundred fifty patients with known infecting genotype for whom posttransplantation biopsy specimens were available or who had normal results of liver injury tests constituted the group analyzed. Patients were followed up for up to 4.5 years. Hepatitis activity index scores at the time of disease recurrence were used to assess disease activity. Cirrhosis was diagnosed by using histological evidence. The number of HLA matches with respect to A, B, DR, and DQ loci was determined. RESULTS: The rates of hepatitis recurrence were 25% and 75% at 1 year and 4 years, respectively; Kaplan-Meier survival analysis did not reveal significant differences between the infecting genotypes with respect to overall rates of survival or recurrence of hepatitis. At hepatitis recurrence, hepatitis activity index scores did not differ between the genotype groups. The distribution of infecting genotypes among the 7 patients who developed cirrhosis is reflective of pretransplantation distribution. Neither HLA site-specific nor total matches affected the rates of survival or disease recurrence. CONCLUSIONS: The infecting HCV genotype had no influence on the incidence or severity of recurrent hepatitis, rate of survival, or development of cirrhosis. HLA matching does not influence transplantation outcome for HCV-related disease.

Adult↗
PubMed1998

Medical costs and lost productivity from health conditions at volatile organic compound-contaminated superfund sites.

This paper estimates the health costs at Superfund sites for conditions associated with volatile organic compounds (VOCs) in drinking water. Health conditions were identified from published literature and registry information as occurring at excess rates in VOC-exposed populations. These health conditions were: (1) some categories of birth defects, (2) urinary tract disorders, (3) diabetes, (4) eczema and skin conditions, (5) anemia, (6) speech and hearing impairments in children under 10 years of age, and (7) stroke. Excess rates were used to estimate the excess number of cases occurring among the total population living within one-half mile of 258 Superfund sites. These sites had evidence of completed human exposure pathways for VOCs in drinking water. For each type of medical condition, an individual's expected medical costs, long-term care costs, and lost work time due to illness or premature mortality were estimated. Costs were calculated to be approximately $330 million per year, in the absence of any remediation or public health intervention programs. The results indicate the general magnitude of the economic burden associated with a limited number of contaminants at a portion of all Superfund sites, thus suggesting that the burden would be greater than that estimated in this study if all contaminants at all Superfund sites could be taken into account.

Anemia↗
PubMed1998

Retrograde infusion of lidocaine or L-arginine before reperfusion reduces myocardial infarct size.

BACKGROUND: Retrograde perfusion preserves ischemic myocardium when initiated shortly after coronary artery occlusion. However, benefits diminish as the delay increases. In this study, we used this technique to deliver agents known to reduce the injury associated with the reperfusion of ischemic myocardium. We proposed that the local delivery of lidocaine or L-arginine before reperfusion would reduce the damage caused during reperfusion, even after a delay between onset of ischemia and intervention designed to approximate clinical reality. METHODS: In a porcine model of myocardial ischemia, the left anterior descending coronary artery was snared immediately distal to its second diagonal branch. After 1 hour of occlusion, 34 animals were randomized into six groups: no intervention (control) (n = 6); administration of normal saline solution into the great cardiac vein (Retro-NS) (n = 6); administration of lidocaine either intravenously (i.v.-LID) (n = 6) or retrograde (Retro-LID) (n = 6); and administration of L-arginine either intravenously (i.v.-L-ARG) (n = 5) or retrograde (Retro-L-ARG) (n = 5). After 90 minutes of ischemia, the snare was released, and the myocardium was reperfused for 3 hours. Two-dimensional echocardiograms were made prior to occlusion and 60, 150, 210, and 270 minutes after occlusion. The infarct size and the area at risk were determined by lissamine green and triphenyltetrazolium chloride staining with computer planimetric quantification. Regional wall motion was assessed by a wall motion score: normal = 1; mild hypokinesia = 2.0; severe hypokinesia = 2.5; and akinesia = 3. RESULTS: The area of the left ventricle at risk for infarction was similar in all groups and represented 25.4% (5.2% [standard deviation]) of the left ventricular mass (p = 0.63). The percent area of infarction in the area at risk after 3 hours of reperfusion was 76.7% (7.1% for the control group, 73.9% (5.7%) for the Retro-NS group, 72.1% (8.7%) for the i.v.-LID group, 54.5% (10.2%) for the Retro-LID group, 58.8% (4.0%) for the i.v.-L-ARG group, and 54.3% (4.0%) for the Retro-L-ARG group p < 0.005, Retro-LID and Retro-L-ARG versus Control, Retro-NS, and i.v.-LID; p < 0.03, i.v.-L-ARG versus control and Retro-NS). No significant difference in wall motion scores between groups was detected by echocardiography (p = 0.578). CONCLUSIONS: Retrograde delivery of lidocaine or L-arginine before reperfusion reduces infarct size without acutely affecting wall motion after 90 minutes of ischemia and 3 hours of reperfusion. Lidocaine must be present before reperfusion to have an effect, whereas L-arginine is beneficial if it is delivered at the time of reperfusion.

Anesthetics, Local↗
PubMed1998

Isolated lung liposome-mediated gene transfer produces organ-specific transgenic expression.

BACKGROUND: Gene therapy is a promising strategy for the treatment of inoperable pulmonary tumors and rejection after lung transplantation. However, unlike ex vivo administration, intravenous in vivo transfection lacks organ specificity and has a limited duration of expression. The objectives of this study were to limit transfection to a single lung and to increase the duration of gene expression in vivo. METHODS: Sixteen male Fisher rats were anesthetized and divided into two groups. Animals in group I (n = 7) received an intrajugular administration of 1,320 microg of chloramphenicol acetyl transferase (CAT) complementary DNA complexed with cationic liposomes. Animals in group II (n = 9) received 660 microg of CAT complementary DNA complexed with cationic liposomes into the pulmonary artery of an isolated left lung over 10 minutes. After 40 minutes of incubation, the lung was flushed with 10 mL of normal saline solution, and the perfusate was suctioned through a left pulmonary venotomy. The circulation to the left lung was then restored. After 48 hours, the animals were divided into subgroups (a and b) and CAT activity was assessed in the lungs, hearts, livers, and kidneys of groups Ia (n = 3) and IIa (n = 5). After 21 days, CAT activity was assessed in the left lungs of groups Ib (n = 4) and IIb (n = 4). RESULTS: After 48 hours, animals that had received intravenous administration of CAT cDNA showed strong expression in the lungs and hearts and negligible expression in the livers and kidneys. In contrast, animals in group IIa, which had received isolated left lung perfusion of CAT cDNA showed expression only in the left lung. After 21 days, the left lungs of animals in group Ib, which had received intravenous administration of CAT complementary DNA, showed no CAT expression, but the left lungs of animals in group IIb, which had received isolated left lung perfusion of CAT complementary DNA, exhibited strong CAT expression. CONCLUSIONS: Compared with intravenous administration, isolated lung liposome-mediated gene transfer provides prolonged organ-specific gene expression. This provides a useful model to study the effects of gene therapy on pulmonary tumors, which may have further application when gene therapy is used in clinical practice.

Animals↗
PubMed1998

Gene therapy in lung transplantation: effective gene transfer via the airways.

OBJECTIVES: Gene therapy may provide a means of modifying factors that contribute to the development of pathologic processes in transplanted lungs. Experiments were designed to study the feasibility of adenovirus-mediated gene transfer by way of the airways to the transplanted lung. METHODS: Orthotopic left lung transplantation (Lewis to Lewis rats) was performed on four groups of animals. 300 microl of adenovirus solution encoding for beta-galactosidase was infused into the left bronchus of donor rats at viral concentrations of 10(8) pfu/ml (n = 5), 10(9) pfu/ml (n = 6), and 10(10) pfu/ml (n = 6), and the lung was ventilated for 5 minutes. Controls (n = 6) received medium only. Seven days after transplantation, native and transduced, transplanted lungs were harvested. Sections of lung were fixed and stained with a solution of X-Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside) and staining was evaluated for distribution by cell type and intensity. RESULTS: Beta-galactosidase expression was absent in the control group and in the native lungs. Two of five lungs in the 10(8) group expressed beta-galactosidase, but in a limited distribution and intensity. All six lungs in the 10(9) group and five of six lungs in the 10(10) group expressed beta-galactosidase. The distribution and intensity of beta-galactosidase expression ranged from only a few cells staining per slide to up to 75%. Pneumocytes were the most frequently stained cell type followed by alveolar macrophages. CONCLUSIONS: Gene transfer to the transplanted lung via the bronchial route is feasible and offers a novel technique to modify pathologic processes in the transplanted lung.

Adenoviridae↗
PubMed1998

Clinical intestinal transplantation: new perspectives and immunologic considerations.

BACKGROUND: Although tacrolimus-based immunosuppression has made intestinal transplantation feasible, the risk of the requisite chronic high-dose treatment has inhibited the widespread use of these procedures. We have examined our 1990-1997 experience to determine whether immunomodulatory strategies to improve outlook could be added to drug treatment. STUDY DESIGN: Ninety-eight consecutive patients (59 children, 39 adults) with a panoply of indications received 104 allografts under tacrolimus-based immunosuppression: intestine only (n = 37); liver and intestine (n = 50); or multivisceral (n = 17). Of the last 42 patients, 20 received unmodified adjunct donor bone marrow cells; the other 22 were contemporaneous control patients. RESULTS: With a mean followup of 32 +/- 26 months (range, 1-86 months), 12 recipients (3 intestine only, 9 composite grafts) are alive with good nutrition beyond the 5-year milestone. Forty-seven (48%) of the total group survive bearing grafts that provide full (91%) or partial (9%) nutrition. Actuarial patient survival at 1 and 5 years (72% and 48%, respectively) was similar with isolated intestinal and composite graft recipients, but the loss rate of grafts from rejection was highest with intestine alone. The best results were in patients between 2 and 18 years of age (68% at 5 years). Adjunct bone marrow did not significantly affect the incidence of graft rejection, B-cell lymphoma, or the rate or severity of graft-versus-host disease. CONCLUSIONS: These results demonstrate that longterm rehabilitation similar to that with the other kinds of organ allografts is achievable with all three kinds of intestinal transplant procedures, that the morbidity and mortality is still too high for their widespread application, and that the liver is significantly but marginally protective of concomitantly engrafted intestine. Although none of the endpoints were markedly altered by donor leukocyte augmentation (and chimerism) with bone marrow, establishment of the safety of this adjunct procedure opens the way to further immune modulation strategies that can be added to the augmentation protocol.

Actuarial Analysis↗