Biomedical subjects

M Ho

Publications and source records attributed to M Ho.

At least 163 records · Page 9Linked to original sources

PubMed1994

Investigation of cytomegalovirus infection as a risk factor for coronary atherosclerosis in the explanted hearts of patients undergoing heart transplantation.

Infection with a human herpes virus, particularly cytomegalovirus (CMV), has been hypothesized to be a cofactor in the development of atherosclerosis in humans. We investigated the association of prior CMV infection with the presence of atherosclerosis in the coronary arteries of the native heart of 314 individuals undergoing heart transplantation. Age, male gender, race, tobacco use, and previous general and cardiac surgery were also studied as covariables. Factors associated with the presence of coronary atherosclerosis by univariate analysis were age greater than the median of 48 years (odds ratio [OR] = 5.9, 95% confidence intervals [CI] 3.0-11.6; P < 0.0001), tobacco use (OR = 3.8, 95% CI 2.1-7.0; P < 0.005), CMV seropositivity (OR = 3.1, 95% CI 1.8-5.5; P < 0.001), and male gender (OR = 3.0, 95% CI 1.6-5.4; P < 0.0005). When patients were divided into quartiles based on age, coronary atherosclerosis was shown to be associated with CMV seropositive status only in the youngest quartile of patients (OR = 3.6, 95% CI 1.4-8.9; P < 0.01) but not in the older three quartiles of patients (OR = 0.9, 95% CI = 0.3-2.4; P > 0.5). In multiple logistic regression analyses, CMV seropositivity was not a significant independent variable in the whole group of patients (P = 0.13) but remained a significant variable in the youngest quartile of patients (P = 0.01). However, 43% of these younger patients and 29% of all patients with coronary atherosclerosis were seronegative for CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Analysis of overlapping T- and B-cell antigenic sites on rubella virus E1 envelope protein. Influence of HLA-DR4 polymorphism on T-cell clonal recognition.

A CTL antigenic site located between residues 273 and 291 of the E1 envelope protein of RV was identified by 51Cr-release assays employing SPs. Two E1-specific CTL clones were examined for immune recognition of RV wild-type and attenuated vaccine strains and recombinant E1 protein. The exact sequence (273-284) recognized by both clones was delineated by using truncated and overlapping SPs covering these residues. The defined T-cell site overlapped almost completely with a virus neutralizing antibody-binding site previously identified with mouse monoclonal and human antibodies. A series of single aa-substituted SP analogues of E1(273-284) was used to define residues critical for T-cell recognition. Using EBV-BL displaying different HLA-DR haplotypes and -DR4 subtypes as targets to determine MHC class II restriction elements, immune recognition by both T-cell clones was shown to be associated with HLA-DR4. Three HLA-DR4 subtypes (DR4Dw13A, DR4Dw13B, and DR4KT2) sharing a common residue, glutamic acid at position 74 in their beta 1 chains, were able to present SP E1(273-284) to the T-cell clones.

Amino Acid Sequence↗

PubMed1994

A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV disease while on zidovudine.

OBJECTIVE: A Phase I study of subcutaneous recombinant interleukin-2 (rIL-2). DESIGN: Sixteen patients with advanced HIV infection receiving 600-1200 mg zidovudine per day were divided into three groups, which received sequentially 0.2 x 10(6), 0.7 x 10(6) or 2 x 10(6) units/m2 per day of rIL-2 subcutaneously 5 consecutive days. SETTING: Five-day admission to an academic tertiary care hospital. PATIENTS, PARTICIPANTS: Sixteen unblinded, non-randomized volunteers. INTERVENTIONS: Subcutaneous rIL-2. MAIN OUTCOME MEASURES: Tolerance, toxicity, hematologic, immunologic and antiviral responses. RESULTS: rIL-2 was well-tolerated at the highest dosage, except in two patients who developed significant lymphopenia by the second day of rIL-2 administration, with rebound within 48 h after rIL-2 therapy. The number of eosinophils, CD4+ and CD8+ cells, and percentage of CD16+ (natural killer) cells, remained elevated above baseline for up to 10 weeks. Circulating rIL-2 receptor levels increased transiently during and immediately following rIL-2 administration. A twofold increase in natural killer cell activity against uninfected and HIV-infected targets was observed, but did not persist beyond 10 weeks following rIL-2 administration. There was a transient decrease in blastogenesis to phytohemagglutinin of patients receiving the highest dose of r-IL-2, but no significant change in viral burden. CONCLUSIONS: Subcutaneous rIL-2 in advanced HIV-infected patients on zidovudine was tolerated with side-effects similar to intravenous IL-2.

Adult↗

PubMed1994

Candida carriage in the alimentary tract of liver transplant candidates.

Thirty randomly selected patients with advanced chronic liver disease, which had been evaluated for possible liver transplantation, were sampled endoscopically at 7 alimentary tract locations to assess the frequency and amount of Candida carriage. Eighty-one percent (127/156) of the samples obtained contained Candida and 53% (82/156) yielded high counts (> 300 CFU/ml). The most predominant Candida species isolated at each site was Candida albicans, which accounted for 103 (64%) of the 160 fungal isolates. The other Candida species isolated included C tropicalis 30 (19%), C krusei 16 (10%), and C glabrata 11 (7%). Although the number of sites at which yeast was present and the quantities of yeast at each site varied widely among the patients studied, 100% of the patients had Candida in at least one site of the gastrointestinal tract. Eighty-six percent (24/28) of the duodenal aspirates contained Candida and 50% (14/28) of the duodenal samples contained greater than 300 CFU/ml. A positive culture from the stomach was a reliable predictor of the presence of Candida in the duodenum (P = 0.0001), but a positive culture at no other site readily predicted the presence of Candida at yet another site. Importantly, there was no correlation between the presence or absence of Candida in either oral or rectal swabs and colonization at other anatomic sites within the gastrointestinal tract. These findings are important in liver transplantation, particularly in those cases in which the bowel has been opened to create a choledochojejunostomy anastomosis. The operative attempts to reduce gastrointestinal fungal carriage using oral antifungal agents may be justified before liver transplantation in an effort to lower the risk of posttransplantation fungal infections, particularly in those patients expected to have a Roux-en-Y choledochojejunostomy biliary reconstruction.

Body Fluids↗

PubMed1994

Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients.

Epstein-Barr virus (EBV) infection is recognized as the principal aetiological factor in the pathogenesis of post-transplant lymphoproliferative disease (PTLD), particularly when primary EBV infection occurs after transplantation. We analysed, using a time-dependent proportional hazards model, the factors associated with development of PTLD in 40 adult liver transplant recipients who were seronegative for EBV prior to transplantation. Of 40 patients, 13 (33%) had a tissue diagnosis of PTLD at a median time of 126 days after transplantation. The multivariate analysis showed that prior CMV disease, the number of steroid boluses given and the number of units of RBC and FFP transfused were significant risk factors for development of PTLD.

Adult↗

PubMed1994

Pharmacokinetics of ceftriaxone in patients with typhoid fever.

Ceftriaxone in short courses has emerged as an effective alternative to chloramphenicol for the treatment of typhoid fever. To study the pharmacokinetics of ceftriaxone in acute typhoid fever, 10 febrile Nepalese adolescents and young adults with blood culture-positive illness were treated with 3 g of ceftriaxone (intravenous infusion for 30 min) daily for 3 days. On the 1st and 3rd day of treatment, blood and urine samples were collected at defined intervals for measurements of drug concentrations. Kinetic parameters including concentrations at the end of infusion (Cmax) and 24 h after the end of infusion (Cmin), elimination half-life (t1/2), area under the plasma concentration-time curve (AUC), total plasma clearance, renal clearance, percentage excreted in urine, and volume of distribution were estimated. On day 1, mean values were as follows: Cmax, 291 micrograms/ml; Cmin, 21.7 micrograms/ml; plasma t1/2, 5.2 h; AUC, 1,428 micrograms.h/ml; total plasma clearance, 37 ml/min; renal clearance, 19 ml/min; percentage excreted in urine, 49.7%; and volume of distribution, 16.1 liters. Mean values on day 3 were not significantly different from those on day 1. Compared with published values for healthy volunteers who received the same dose, our mean t1/2s and AUCs were lower and our mean total plasma clearances, renal clearances, and volumes of distribution were higher. The good clinical responses of these patients to therapy and the adequate Cmins support the use of ceftriaxone once daily for the treatment of typhoid fever.

Adolescent↗

PubMed1994

Polyclonal expansion of peripheral gamma delta T cells in human Plasmodium falciparum malaria.

Plasmodium falciparum malaria in humans is associated with an increase in the percentage and absolute number of gamma delta T cells in the peripheral blood. This increase begins during the acute infection phase and persists for at least 4 weeks during convalescence. In the present study, 25 to 30% of the gamma delta T cells expressed HLA-DR antigens in vivo and in some patients they proliferated in response to further stimulation by purified human interleukin 2 in vitro. However, there was no in vitro proliferative response to various malarial antigens, including a 75-kDa heat shock protein and a 72-kDa glucose-regulated protein of P. falciparum during the acute infection phase. Cytofluorographic studies showed that although an increase of V delta 1- gamma delta T cells was largely responsible for the expansion of the total number of gamma delta T cells, there was also a proportional increase in V delta 1+ cells. These results were confirmed with anchored PCR and by DNA sequencing to characterize at the molecular level the set of T-cell receptor (TCR) delta mRNAs expressed in the peripheral blood of two patients with high levels of gamma delta T cells. In each case, most of the TCR delta mRNA transcripts corresponded to nonproductively rearranged delta genes (unrearranged J delta or near J delta spliced to C delta). In those sequences which did represent productively rearranged genes, most of the transcripts originated from a V delta 2/J delta 1 joining, as in normal individuals. A minority of transcripts originated from a V delta 1/J delta 1 rearrangement, and one originated from a V alpha 4/J delta 1 rearrangement. Polyclonal activation of gamma delta T cells was inferred from the extensive junctional diversity seen in the delta mRNAs analyzed. Expansion of a heterogeneous set of both V delta 1(-)- and V delta 1(+)-bearing T cells suggests that the elevated levels of gamma delta T cells seen during acute P. falciparum malaria arose from immune responses to multiple distinct parasite antigens or unidentified host factors.

Adult↗

PubMed1994

Diagnosis of cytomegalovirus infections by shell vial assay and conventional cell culture during antiviral prophylaxis.

A total of 3,552 specimens for conventional cytomegalovirus (CMV) culture and shell vial assay for CMV immediate-early antigen were obtained during a prospective randomized trial for prophylaxis of CMV disease after liver transplantation. Prophylaxis with ganciclovir for 2 weeks and then high-dose acyclovir for 2.5 months was compared with high-dose acyclovir alone for 3 months. During the first 12 weeks after transplantation, when the patients were on prophylaxis, there were significantly more clinical samples positive by the shell vial assay and negative by standard culture in comparison with the number of samples obtained from weeks 13 to 24, after prophylaxis was discontinued, that were positive by the shell vial assay and negative by standard culture. In contrast, significantly fewer samples were positive by both the shell vial assay and standard culture during the first 12 weeks compared with the number obtained 13 to 24 weeks after transplantation that were positive by both methods. Samples positive by the shell vial assay only were obtained significantly more frequently from patients with asymptomatic than symptomatic CMV infections, while samples positive by both methods were obtained significantly more often from patients with symptomatic CMV infection. It was concluded that antiviral prophylaxis with high-dose acyclovir or ganciclovir and then high-dose acyclovir and asymptomatic CMV infection are associated with a decrease in the level of CMV isolation by standard cell culture in comparison with that by the shell vial assay.

Acyclovir↗

PubMed1994

EBV gene expression, EBNA antibody responses and EBV+ peripheral blood lymphocytes in post-transplant lymphoproliferative disease.

Epstein-Barr virus (EBV) is associated with the development of several B cell malignancies including Burkitt's lymphoma (BL), post-transplant lymphoproliferative disease (PTLD), and AIDS-related lymphomas. The latter two diseases result from EBV-driven B cell proliferation in the absence of normal immunosurveillance and as such, represent a heterogenous family of lymphoproliferative disorders. This article reviews studies on EBV gene expression and antibody development in PTLD and introduces recent information on the levels of EBV+ peripheral blood lymphocytes to discuss possible mechanisms of pathogenesis under varying conditions of immunosuppression.

Animals↗

PubMed1994

Advances in understanding cytomegalovirus infection after transplantation.

Susceptibility to infection and disease caused by CMV varies with the degree of immunosuppression, the antecedent immunity to CMV, the source of the virus, and a complex set of host responses. These responses include the development of humoral and cellular immunity and also immunopathologic responses. HLA-restricted responses may facilitate CMV disease by facilitating the survival and activation of latently infected cells, or by facilitating MHC-class I or class II cellular immune responses underlying both protective effects and pathologic inflammation.

Cytomegalovirus↗

PubMed1994

Detection of cytomegalovirus in formalin-fixed paraffin-embedded donor, native and allograft liver tissue using a multiplex polymerase chain reaction-liquid hybridization assay.

A multiplex polymerase chain reaction (PCR)-liquid hybridization assay detecting a minimum 10 fg of cytomegaloviral (CMV) DNA has been developed. This assay successfully detected viral nucleic acids in 25/26 (96.2%) routinely embedded allograft liver biopsies with CMV hepatitis. No CMV DNA was detected in 15 native and 12 donor liver tissues sampled at the time of liver transplantation. These results indicate that archived formalin-fixed, paraffin-embedded liver tissues obtained from patients with significant liver disease can be successfully analyzed for CMV by PCR, retrospectively. Failure to detect CMV in native and donor livers implies that any latent virus present within these tissues is very focally distributed, or is below the threshold of detection applicable to PCR.

Base Sequence↗

PubMed1993

Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus.

Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.

AIDS-Related Complex↗

PubMed1993

A phase 1 study of adoptive transfer of autologous CD8+ T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS.

Based on preclinical studies showing that CD8+ T lymphocytes of human immunodeficiency syndrome (HIV)-infected subjects have anti-HIV activities, a phase 1 study was undertaken to determine the safety and feasibility of infusing in vitro purified, activated, and expanded CD8+ cells as a therapeutic measure in seven patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Autologous CD8+ cells were first selectively isolated in monoclonal antibody-coated flasks from peripheral blood mononuclear cells recovered by leukapheresis. They were then cultured and expanded with phytohemagglutinin and recombinant interleukin-2 (rIL-2) before infusion. Five cycles of isolations and infusions of increasing numbers of CD8+ T cells were achieved in five of seven subjects. Five cycles could not be completed in two subjects with AIDS whose CD4+ cell counts were < or = 48/microliters. Infusions of CD8+ cells alone were well tolerated. Four patients received rIL-2 by continuous infusion for 5 days with their final cycle of CD8+ cells. All developed reversible adverse effects attributable to rIL-2. After infusion, 111In-labeled CD8+ cells quickly accumulated in the lungs, with less than 10% of the labeled cells remaining in the circulation. After 24 hours, labeled CD8+ cells were reduced in the lungs, but increased and persisted in liver, spleen, and bone marrow. Four of five patients who were treated with multiple infusions of CD8+ cells have improved or remained clinically stable, and the fifth developed Pneumocystis carinii pneumonia but recovered. This study demonstrated that infusion of autologous, in vitro expanded and activated CD8+ cells was feasible and clinically well tolerated in five of seven subjects with advanced HIV infections.

AIDS-Related Complex↗

PubMed1993

Evidence for restricted Epstein-Barr virus latent gene expression and anti-EBNA antibody response in solid organ transplant recipients with posttransplant lymphoproliferative disorders.

Epstein-Barr virus (EBV) is associated with the development of two human B-cell malignancies, Burkitt's lymphoma and lymphomas that occur in the immunosuppressed host. The latter category of disease has become important recently as it is seen primarily in organ transplant recipients and individuals with acquired immunodeficiency syndrome. One possible mechanism for lymphoma development involves a reduction in or lack of EBV-specific cytotoxic T-cell recognition. In support of this model are previous observations that the expression of EBV nuclear antigen 2 (EBNA2) and latent membrane protein, two viral antigens associated with major histocompatibility complex class I-restricted T-cell killing, are downregulated in Burkitt's lymphoma and in early passage lymphoblastoid cell lines (LCL) derived from the malignant lesions. To determine whether a similar mechanism could occur in the development of posttransplant lymphoproliferative disorders (PTLD), we compared EBV gene expression among 23 PTLD tumor lesions obtained from 11 solid organ transplant recipients and among LCL derived from 3 of these lesions. In this report, we demonstrate, by Southern blot, Western blot, and immunofluorescence analysis, that (1) the tumor lesions exhibit varying patterns of restricted viral gene expression; (2) LCL derived from these lesions may represent the in vitro selection of cell subpopulations; and (3) immunosuppressed individuals have a markedly reduced antibody response to the latent cycle antigens, EBNA1, EBNA2, and EBNA-LP, but not to the lytic cycle viral capsid antigen when compared with normal immunocompetent controls.

Adolescent↗

PubMed1993

Effects of adoptive immunotherapy with autologous CD8+ T lymphocytes on immunologic parameters: lymphocyte subsets and cytotoxic activity.

CD8+ cytotoxic T lymphocytes (CTL) may be an important parameter of host resistance to HIV infection. The present study determined whether CD8+ cells could be purified and propagated in vitro to enhance anti-HIV CTL activity, and the immunologic effects of infusion of these cells into autologous, HIV-infected patients as a potential immunotherapy for AIDS and AIDS-related complex (ARC). CD8+ lymphocytes from five AIDS and ARC patients were purified from leukapheresis preparations in cell culture flasks coated with CD8-specific monoclonal antibodies and propagated in vitro for 3 weeks. The ex vivo propagated cells were 98% (+/- 1%) CD8+ and 43% (+/- 6%) HLA-DR+. The majority of the CD8+ cell preparations had increased lytic activity against autologous B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-IIIb structural proteins gag, pol, or env, relative to that of fresh blood mononuclear cells tested prior to purification and culture. The results also show for the first time that CD8+ CTL from HIV-infected patients can lyse cells expressing the HIV regulatory protein, tat. Enhanced expression of CD56 (natural killer cell marker) and lytic activity against vaccinia virus control vector-infected, autologous targets were also noted in the CD8+ cell preparations. Infusion of the CD8+ CTL into autologous patients was well-tolerated and resulted in low but discernible, temporal increases in circulating cytotoxic activity against the HIV gene-expressing targets.

AIDS-Related Complex↗

PubMed1993

The impact of blood transfusion on the occurrence of pneumonitis in primary cytomegalovirus infection after liver transplantation.

The influence of blood transfusion, and particularly the transfusion of blood from cytomegalovirus (CMV)-seropositive donors, on the incidence of primary CMV infection following liver transplantation was studied prospectively in 29 consecutive CMV-seronegative adult liver transplant recipients. Fourteen patients received a liver graft from a CMV-seropositive donor (Group A), whereas for 15 patients, the donor was CMV seronegative (Group B). Eleven patients (79%) in Group A but only two (13%) in Group B developed CMV infection (odds ratio, 23.8; 95% confidence interval, 3.5-169.4). In five Group A patients, primary CMV infection resulted in pneumonitis. There was no statistical difference in the total number of blood units and the number of units of CMV-seropositive blood given to patients who did or did not develop CMV infection in both Groups A and B (odds ratio for unit of CMV-seropositive blood transfused, 1.07; 95% confidence interval, 0.96-1.19). However, Group A patients who developed CMV pneumonitis received a higher total number of blood units (median, 44) and of CMV-seropositive blood units (median, 18) than did patients who developed other CMV infections (asymptomatic CMV, CMV syndrome, or CMV hepatitis), who received a median of 9 total units of blood and 5 units of CMV-seropositive blood (p = 0.004). It is concluded that the total number of blood units and of CMV-seropositive blood units transfused does not have an effect on the incidence of primary CMV infection after liver transplantation, but it does have an impact on the severity of the infection in recipients of a CMV-seropositive allograft.

Blood Transfusion↗

PubMed1993

Malaria in splenectomized patients: report of four cases and review.

The spleen plays a central role in host defense against malaria in animals. Its role in human malaria is less well established. The spleen may contribute to protection against human malaria by mediating humoral or cellular immune responses or by clearing both rheologically and immunologically altered host erythrocytes. This report describes Plasmodium falciparum and Plasmodium vivax infections that occurred after splenectomy in one nonimmune and three partially immune Thai adults. The clinical course was uncomplicated for all four patients, and parasite clearance was delayed only in the nonimmune patient. In three patients with falciparum malaria, humoral and cellular immune responses to blood-stage antigens during the acute infection and convalescence were similar to those of individuals whose spleens were intact. These findings suggest that the spleen may not be essential for the processes leading to parasite clearance in partially immune, splenectomized patients. Further studies on the course of malarial infections in splenectomized patients are crucial for clarifying the role of the spleen in host defense against human malaria.

Adult↗

PubMed1993

Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy.

To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-gamma), and cytokine receptors (tumor necrosis factor receptor [TNF-R] p55 and TNF-R p75) were measured in the plasma of 29 adult Nepalese with culture-positive typhoid fever before therapy and on days 4 and 15 after start of therapy with either ceftriaxone at 2 g/day for 3 days or chloramphenicol at 50 mg/kg of body weight per day for 14 days. Bacteriologic cure was defined as blood cultures testing negative on days 4 and 15 after start of therapy; clinical cure was defined as symptomatic improvement within 5 days after start of therapy and absence of relapse. Clinical and bacteriologic cures occurred in 24 patients. There were two clinical failures, two patients who failed to complete therapy because of leukopenia, and one relapse. Mean levels before therapy were elevated compared with those in healthy controls (IL-6, 11.4 pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and fell progressively during and after therapy. For six patients (three in each treatment group) who showed prolonged fever (> 5 days) or relapse, mean levels of IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P < .05). These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever and that these concentrations can be useful in predicting outcome.

Adolescent↗