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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 667 records · Page 37Linked to original sources
PubMed1991

Detection of antibody to hepatitis C virus in renal transplant recipients.

Non-A, non-B hepatitis is a significant cause of liver disease among renal allograft recipients. In order to assess the impact and prevalence of hepatitis C in a series of renal allograft recipients, we retrospectively screened 621 consecutive patients transplanted between 1979 and 1989 and 484 cadaver organ donors retrieved in the same interval for serologic evidence of hepatitis C viral (HCV) infection using the enzyme-linked assay for anti-HCV antibody. Of 596 HBsAg negative patients, 180 (30%) were anti-HCV positive at the time of transplant. One-year posttransplant, 117 (22%) had detectable levels of anti-HCV antibody. Chemically significant hepatitis developed in 52/234 (22%) anti-HCV positive patients, and 26 of these followed a clinical course consistent with chronic hepatitis. Significantly more males and patients with antibody to HCV detectable at 1 year posttransplant were in the group experiencing an increase in liver enzymes. Ten-year patient and graft survival was 78% and 50%, respectively, for the anti-HCV positive patients who had an elevation of alanine aminotransferase, and 76% and 57% for the cohort maintaining normal liver function (P = NS). There were also no differences in patient and graft survival among the anti-HCV positive group and the consistently sero-negative patients. Of 484 cadaver organ donors with serum available for analysis (out of 1200 retrieved), 67 (14%) were anti-HCV positive at the time of organ donation. Among 23 anti-HCV negative kidney recipients who received a kidney from an HCV antibody positive donor, only one had seroconverted at 1 year posttransplant. Antibody to HCV appears to be widespread among renal transplant recipients and cadaver organ donors. We were unable to demonstrate any evidence of long-term adverse effects on patient and graft survival among anti-HCV positive patients employing the first generation anti-HCV assay.

Adult↗
PubMed1991

The effects of tissue-associated and MHC class II antigen presentation on in vitro lymphoproliferative responses against canine liver and kidney cell subpopulations.

Purified hepatocytes (LH), Kupffer cells (LKu), and intrahepatic biliary duct cells (LD) were isolated from canine livers, as well as tubular cells from canine kidneys, by enzymatic digestion, gradient centrifugation, and tissue culture techniques. Incubation of LH, LKu, and LD for 48 hr in a two-compartment diffusion chamber opposite two-way mixed lymphocyte cultures, or with canine gamma interferon purified and standardized in our laboratory, resulted in a significant increase in class II expression. This was detected in the cell analyzer with directly fluoresceinated B1F6, a monoclonal antibody (mab) generated in our laboratory vs. a canine class II monomorphic epitope. An amplification of the allogeneic mixed lymphocyte liver cell cultures (MLLC) of at least 2-fold was observed by preinduction of canine class II expression with IFN-gamma on LKu and LD cells, but an autologous reaction could not be elicited. However, an autologous as well as allogeneic lymphoproliferation against kidney tubular cells (MLKC) could be easily observed without IFN-gamma and amplified with IFN-gamma to stimulation indices of at least 3 times that of noninduced cultures. Dependence of the allogeneic MLLC and allogeneic and autologous MLKC on class II gene expression was also evidenced by blocking of 3H-thymidine uptake seen by incubation with 5 micrograms of B1F6. Another mab, I1F6, generated against tubular cells and inhibiting the autologous and allogeneic MLKC, had no blocking effect on lymphoproliferation with any of the liver cell preparations. No such tissue-specific mab (analogous to I1F6) has thus far been found in response to mouse immunization with LH, LKu, or LD. In the absence of accepted defined molecular probes in the dog as yet, we conclude that, in contrast to kidney tubular cells, cells of the normal canine liver do not readily stimulate a primary lymphoproliferative autoimmune reaction in vitro despite class II amplification. Thus autoreactivity (as opposed to alloreactivity) is much less prominent in immune recognition of purified cellular components of nondiseased liver tissue than of kidney tissue in which tissue-associated epitopes are more operative.

Animals↗
PubMed1991

Evidence that antibodies to cytomegalovirus and the T cell receptor (TCR)/CD3 complex may have common ligands.

Immunoglobulins derived from sera containing anti-antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, alpha F1, another MAb recognizing the framework of the TCR alpha chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, alpha F1 showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a approximately 50 KD band of TCML and several bands (approximately 34, approximately 40, and approximately 50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, alpha F1 immunoprecipitated a approximately 96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipitable with LAb. Both LAb and alpha F1 also showed positive binding to paraformaldehyde-fixed and Triton X-100-permeabilized PBT in flow cytometry. Sera containing Ab2 blocked alpha F1 binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both alpha F1 and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.

Antibodies, Monoclonal↗
PubMed1991

Correlation of RFLP typing and MLC reactivity in dogs.

The human recombinant HLA-DRB1 gene probe was used for histocompatibility typing of two families of beagles for the DLA-D equivalent by using restriction fragment length polymorphisms (RFLP). This method was able to determine the segregation of these genes from the parental animals to the individual F1 offspring. Mixed lymphocyte culture (MLC) reactivity as well as serological typing for class I histocompatibility antigens were also performed for comparison. It was found that there was a high correlation between these three methods. We therefore conclude that RFLP typing is an effective procedure for predicting MLC reactivity in dogs and propose that it is a suitable genotyping method for assignment of class II antigen compatibility for donor-recipient pairs in conjunction with organ transplant studies.

Animals↗
PubMed1991

Cervical papillomavirus infection and cervical dysplasia in Hispanic, Native American, and non-Hispanic white women in New Mexico.

BACKGROUND: Human papillomavirus infections of the cervix are found with varying frequencies in different populations worldwide, and have been associated with cervical cytologic abnormalities. METHODS: We studied 1,603 randomly selected Hispanic, Native American, and non-Hispanic White women in New Mexico to determine the prevalence of cervical HPV infection in these ethnic groups, and its association with Pap smear abnormalities, using a new commercial dot-blot hybridization assay. RESULTS: Nine percent of all women screened had evidence of cervical HPV infection (13.7% of non-Hispanic White women, 9.7% of Hispanics, and 6.6% of Native American women). Prevalence was higher in younger women ages 14-19 years than in older age groups. Over half of women with cervical HPV infection (n = 145) had normal Pap smears. The proportion of infected women increased among those with more advanced cytopathologic abnormalities; 5.6 percent with normal Pap smears had cervical HPV vs 66.7 percent with moderate-severe dysplasia. CONCLUSIONS: Cervical HPV infection is common among New Mexico clinic attendees, varies in prevalence among the three major ethnic groups, and is strongly associated with cervical cytopathologic abnormalities.

Adolescent↗
PubMed1991

Molecular cloning and structure of the human transforming growth factor-beta 2 gene promoter.

Genomic DNA extending over 10 kb 5' of the transforming growth factor-beta 2 (TGF-beta 2) coding region was isolated from a human lung fibroblast lambda phage library. A 5.6 kb Hind III fragment containing the 5'-untranslated region and flanking sequences was subcloned and sequenced. S1 nuclease protection analysis identified a transcriptional initiation site 1357 nucleotides 5' of the methionine initiation codon (ATG). A "TATA box" consensus sequence was identified 30 bp from this transcriptional start site; however, consensus "CAT box" sequences were not observed. Approximately 50 nucleotides of homopurine-pyrimidine [d(GA.CT)50] sequence were identified in the 5'-untranslated region, as well as two short open reading frames of 5 and 45 amino acids. Several AP-1, AP-2, CRE and SP1-like DNA consensus sequence elements were also identified surrounding the transcription initiation site. 5'-deletion mutants of the promoter region were fused to the chloramphenicol acetyl transferase (CAT) gene and promoter activity of the isolated genomic DNA was demonstrated in several cell lines. DNA constructs containing nucleotides between -508 to +63 demonstrated high levels of promoter activity. However, sequences between -778 and -508 nucleotides modulated this promoter activity in a manner which was dependent upon the cell line utilized, suggesting that regulation of TGF-beta 2 gene transcription may be dependent upon the cellular background. The TGF-beta 2 promoter is markedly different from the promoters that have been recently characterized for TGF-beta 1 and TGF-beta 3.

Amino Acid Sequence↗
PubMed1991

Bias produced by fast guessing in distribution-based tests of race models.

A comparison involving cumulative probability distributions of reaction time (RT) has been used to test race models of the redundancy gain observed in certain divided-attention paradigms. It has been pointed out, however, that the presence of fast guesses would interfere with this test, biasing it to accept race models. The present paper reports simulations carried out to determine the size of the bias introduced by fast guesses. In absolute terms, this bias can be quite large--exceeding 175 msec in some conditions. Simulations indicate that the bias increases with the percentage of fast guesses and with the latency difference between the lower tails of guess and nonguess RT distributions. Discarding and rerunning errors reduces bias somewhat, but a more elaborate "kill-the-twin" procedure reduces it much more.

Attention↗
PubMed1991

The flanker compatibility effect as a function of visual angle, attentional focus, visual transients, and perceptual load: a search for boundary conditions.

When subjects must respond to a relevant center letter and ignore irrelevant flanking letters, the identities of the flankers produce a response compatibility effect, indicating that they are processed semantically at least to some extent. Because this effect decreases as the separation between target and flankers increases, the effect appears to result from imperfect early selection (attenuation). In the present experiments, several features of the focused attention paradigm were examined, in order to determine whether they might produce the flanker compatibility effect by interfering with the operation of an early selective mechanism. Specifically, the effect might be produced because the paradigm requires subjects to (1) attend exclusively to stimuli within a very small visual angle, (2) maintain a long-term attentional focus on a constant display location, (3) focus attention on an empty display location, (4) exclude onset-transient flankers from semantic processing, or (5) ignore some of the few stimuli in an impoverished visual field. The results indicate that none of these task features is required for semantic processing of unattended stimuli to occur. In fact, visual angle is the only one of the task features that clearly has a strong influence on the size of the flanker compatibility effect. The invariance of the flanker compatibility effect across these conditions suggests that the mechanism for early selection rarely, if ever, completely excludes unattended stimuli from semantic analysis. In addition, it shows that selective mechanisms are relatively insensitive to several factors that might be expected to influence them, thereby supporting the view that spatial separation has a special status for visual selective attention.

Attention↗
PubMed1991

Double-blind comparison of cetirizine and placebo in the treatment of seasonal rhinitis.

The efficacy and safety of cetirizine were evaluated in 419 patients with seasonal allergic rhinitis. Using a 4-way, double-blind randomization schedule, patients were given a 1-week course of once daily cetirizine (5, 10, or 20 mg) or placebo. Patient and physician efficacy ratings corresponded, indicating superiority of cetirizine to placebo (P less than .05) in reducing symptom severity scores for sneezing, rhinorrhea, ocular pruritus, nasal pruritus, watering of the eyes, and redness of the eyes. All cetirizine doses achieved higher efficacy ratings (72.7%, 79.2%, and 75.7%, respectively) than placebo (52.9%; P less than .05) by the physician's global assessment. Cetirizine was well tolerated, with sedation being the most common adverse experience, increasing in frequency at higher doses. A dose-response relationship was evident for selected symptoms, and the once daily 5-mg dose was found to be an effective minimum dose.

Adult↗
PubMed1991

A comparison of bacterial resistance to antimicrobials in Riyadh, Medina, and Oklahoma City.

Many bacteria are known to develop resistance to anti-microbial agents following their clinical use. The resistance pattern varies from one geographic location to another depending upon the patient population and local history of antibiotic use. The bacterial resistance to commonly used antimicrobial agents in Oklahoma City was found to be different from two cities in Saudi Arabia, especially amongst Gram-negative bacilli. A total of 13,575 fresh clinical isolates from the Veterans Administration Medical Center (VAMC), Oklahoma City, Oklahoma; the King Faisal Specialist Hospital and Research Centre (KFSH), Riyadh; and the King Fahad Hospital (KFH), Medina, Saudi Arabia; were used. There were 6,270 isolates of Enterobacteriaceae, 2,799 pseudomonads and Acinetobacter, and 4,506 Gram positive strains of staphylococcus bacteria. Gram-negative bacteria from KFH were considerably more resistant to ampicillin, gentamicin, and trimethoprim-sulfamethoxazole than at KFSH and VAMC. On the other hand, Staphylococcus aureus isolated from VAMC exhibited a significantly higher degree of resistance to oxacillin and trimethoprim-sulfamethoxazole than those at KFSH and KFH.

Anti-Bacterial Agents↗
PubMed1991

Cure with low-dose total-body irradiation of the hematological disorder induced in mice with the Friend virus: possible mechanism involving interferon-gamma and interleukin-2.

The effects of split low-dose total-body irradiation (TBI; 150 cGy) on production of interferon (IFN)-gamma and Interleukin-2 (IL-2) and on the growth characteristics of erythroid progenitor cells (BFU-E) have been assessed in normal mice, normal mice receiving TBI only, mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P), and FVC-P infected mice receiving 150 cGy TBI on days 5 and 12. It was found that lymphocytes from the spleens of TBI-treated mice previously infected with FVC-P produced in response to phytohemagglutinin (PHA) and concanavalin A (Con A) stimulation up to 15 times greater amounts of IFN-gamma than cells from untreated FVC-P-infected mice. IL-2 production in Con A-stimulated spleen cell cultures also increased when cells were isolated from FVC-P-infected mice treated by low-dose TBI compared to untreated FVC-P-infected mice. TBI treatment was associated with greater than 99% ablation of "erythropoietin-independent" BFU-E colony formation. The results suggest that the cure of FVC-P-infected mice by low-dose TBI may result from activation of the IFN-gamma system and IL-2 production.

Animals↗