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Biomedical subjects

J H Nguyen

Publications and source records attributed to J H Nguyen.

13 recordsLinked to original sources
PubMed1998

Is cytomegalovirus infection related to mycophenolate mofetil after kidney transplantation? A case-control study.

Three multicenter studies have shown that the addition of mycophenolate mofetil (MMF) to an immunosuppressive regime consisting of cyclosporin A (CSA) and prednisone (PRED) decreases the incidence of acute rejection episodes when compared with azathioprine (AZA) or placebo (1-3). In those patients receiving 3 g/d of MMF, the highest dose used in the studies, there was a trend towards an increased incidence of cytomegaloviral sepsis (CMV). We postulated therefore that MMF may represent an independent risk factor for the development of CMV infection in patients receiving renal allografts and MMF at our institution. Having altered the triple drug regime from CSA, AZA (2-2.5 mg/kg/d) and PRED to CSA, MMF (2 g/d) and PRED in July 1995, we elected to study all patients undergoing kidney transplantation for the 33-month period January 1994-September 1996, by undertaking a case control analysis to determine independent risk factors for the development of CMV infection, as defined by CMV viremia or tissue-invasive CMV. Three CMV disease-free control patients were matched to each case, these patients having been randomly selected from the entire pool of patients in the observation period. There were 31 CMV case patients and 102 control patients. Univariate analysis indicated that gender, a concomitant pancreas transplant, acute rejection and CMV seropositivity in the donor were risk factors. However, multivariate analysis indicated that only acute rejection and donor CMV seropositivity were independently linked (p < 0.05) to CMV disease in this sample. Specifically, the odds ratio (OR) for CMV disease between MMF and AZA was 1.0 (95% confidence interval (CI): 0.46-2.18). Therefore, in this case control study we find no evidence that MMF at a dose of 2 g/d is an independent risk factor for primary CMV viremia or tissue invasion in renal allograft recipients.

Adult↗
PubMed1997

A temporal database mediator for protocol-based decision support.

To meet the data-processing requirements for protocol-based decision support, a clinical data-management system must be capable of creating high-level summaries of time-oriented patient data, and of retrieving those summaries in a temporally meaningful fashion. We previously described a temporal-abstraction module (RESUME) and a temporal-querying module (Chronus) that can be used together to perform these tasks. These modules had to be coordinated by individual applications, however, to resolve the temporal queries of protocol planners. In this paper, we present a new module that integrates the previous two modules and that provides for their coordination automatically. The new module can be used as a standalone system for retrieving both primitive and abstracted time-oriented data, or can be embedded in a larger computational framework for protocol-based reasoning.

Artificial Intelligence↗
PubMed1996

Mutations in the poliovirus 3CD proteinase S1-specificity pocket affect substrate recognition and RNA binding.

Sequence and structure comparisons with homologous trypsin-like serine proteases have predicted the S1-specificity pocket in picornavirus 3C proteinases. In this study, we examine the putative roles of such residues in poliovirus 3C substrate recognition. Single amino acid substitutions at 3C residues Thr-142, His-161, Gly-163, Gly-164, and Ala-172 were introduced into near full-length poliovirus cDNAs, and protein processing was examined in the context of authentic 3C cis cleavage activity. Our data are consistent with residues Thr-142, His-161, Gly-163, and Gly-164 acting as important determinants of 3C substrate specificity and support published models of 3C protein structure. An in vivo analysis of mutant viruses containing individual amino acid substitutions at 3C residues Thr-142 and Ala-172 suggests that such residues are important determinants for viral RNA replication. In addition, bacterially expressed, recombinant 3CD polypeptides containing amino acid substitutions at Thr-142 and Ala-172 show altered RNA binding properties in mobility shift assays that use a synthetic RNA corresponding to the poliovirus 5'-terminal sequences.

3C Viral Proteases↗
PubMed1995

Ischemia-reperfusion injury of the spinal cord: the influence of normovolemic hemodilution and gradual reperfusion.

Recent studies have suggested that oxygen-derived free radicals play an important role in ischemia-reperfusion injury of the spinal cord. In other organ systems, reperfusion injury has been reduced by limiting the availability of oxygen in the reperfusion phase. The purpose of this study was to test the effect of normovolemic hemodilution and gradual reperfusion on spinal cord function after aortic cross-clamping in 84 New Zealand White rabbits. All animals underwent 21 min of infrarenal aortic cross-clamping in the conscious state by means of a previously placed aortic occlusion device and were randomized to four groups. Group 1 animals were hemodiluted to a mean (s.e.m.) hematocrit of 28(2)% by extracting 25% of the effective blood volume and reinfusing the plasma component after centrifugation concurrently with a volume of normal saline three times that of the discarded red cells. Group 2 animals (controls) were bled similarly but both plasma and red cells were reinfused, resulting in a mean (s.e.m.) hematocrit of 38(2)%. In the next two groups, distal aortic flow was recorded via an implantable Doppler device. After cross-clamping, flow was returned gradually over 45 min in animals of group 3, and abruptly in group 4. Animals were observed for 5 days and neurologic function was graded by an independent observer. Paraplegia at 5 h after clamping occurred in 75% of animals in group 1 versus 32% in group 2 (P < 0.05), and in 33% of group 3 versus 28% in group 4 (not significant). Of those animals showing initial neurologic recovery, delayed-onset paraplegia was seen in 100% in group 1 versus 87% in group 4 (not significant), and in 50% of group 3 versus 92% of group 4 (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

RNA-protein interactions directed by the 3' end of human rhinovirus genomic RNA.

The replication of a picornavirus genomic RNA is a template-specific process involving the recognition of viral RNAs as target replication templates for the membrane-bound viral replication initiation complex. The virus-encoded RNA-dependent RNA polymerase, 3Dpol, is a major component of the replication complex; however, when supplied with a primed template, 3Dpol is capable of copying polyadenylated RNAs which are not of viral origin. Therefore, there must be some other molecular mechanism to direct the specific assembly of the replication initiation complex at the 3' end of viral genomic RNAs, presumably involving cis-acting binding determinants within the 3' noncoding region (3' NCR). This report describes the use of an in vitro UV cross-linking assay to identify proteins which interact with the 3' NCR of human rhinovirus 14 RNA. A cellular protein(s) was identified in cytoplasmic extracts from human rhinovirus 14-infected cells which had a marked binding preference for RNAs containing the rhinovirus 3' NCR sequence. This protein(s) showed reduced cross-linking efficiency for a 3' NCR with an engineered deletion. Virus recovered from RNA transfections with in vitro transcribed RNA containing the same 3' NCR deletion demonstrated a defective replication phenotype in vivo. Cross-linking experiments with RNAs containing the poliovirus 3' NCR and cytoplasmic extracts from poliovirus-infected cells produced an RNA-protein complex with indistinguishable electrophoretic properties, suggesting that the appearance of the cellular protein(s) may be a common phenomenon of picornavirus infection. We suggest that the observed cellular protein(s) is sequestered or modified as a result of rhinovirus or poliovirus infection and is utilized in viral RNA replication, perhaps by binding to the 3' NCR as a prerequisite for replication complex assembly at the 3' end of the viral genomic RNA.

Base Sequence↗
PubMed1994

Ischemia-reperfusion injury of the spinal cord: protective effect of the hydroxyl radical scavenger dimethylthiourea.

PURPOSE: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. METHODS: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. RESULTS: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). CONCLUSIONS: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.

Animals↗
PubMed1994

Protecting the ischemic spinal cord during aortic clamping: the influence of selective hypothermia and spinal cord perfusion pressure.

PURPOSE: We verified the hypothesis that selective deep hypothermia of the spinal cord during double thoracic aortic clamping can prevent postoperative paraplegia in dogs. METHODS: Normal saline solution was circulated from the cisterna magna through an extracorporeal perfusion system consisting of a reservoir, a pump, and a heat exchanger, back into the subarachnoid space at the level of the medullary cone at a rate of 25 ml/min, starting 30 minutes before clamping, and ending after removal of the clamps. The thoracic aorta was cross-clamped below the left subclavian artery and above the diaphragm for a period of 45 minutes. Cerebrospinal fluid, intracranial, and central venous pressure and aortic pressure proximal, between, and distal to the clamps were continuously recorded. In five dogs, temperature of the circulating normal saline solution at the inflow level was maintained at 2 degrees +/- 1.5 degrees C (group 1), in five controls at 37 degrees +/- 0.8 degrees C (group 2). Five dogs underwent continuous cerebrospinal fluid drainage starting before clamping until sacrifice (group 3). Dogs were observed for up to 4 days, and neurologic function was graded by an independent observer with the Tarlov scale. Animals were then killed, and their spinal cords were prepared for microscopic examination. RESULTS: Hemodynamic parameters were not significantly different between groups. All dogs in groups 2 and 3 were paraplegic with histologic evidence of spinal cord infarction. All animals in group 1 were neurologically normal without microscopic evidence of infarction (p < 0.005). CONCLUSIONS: Selective deep hypothermia of the spinal cord prevents paraplegia after 45 minutes of double aortic clamping in dogs. Cerebrospinal fluid drainage was not effective in preventing paraplegia in this model.

Animals↗
PubMed1993

Minimum internal ribosome entry site required for poliovirus infectivity.

Translation initiation by internal ribosome binding is a recently discovered mechanism of eukaryotic viral and cellular protein synthesis in which ribosome subunits interact with the mRNAs at internal sites in the 5' untranslated RNA sequences and not with the 5' methylguanosine cap structure present at the extreme 5' ends of mRNA molecules. Uncapped poliovirus mRNAs harbor internal ribosome entry sites (IRES) in their long and highly structured 5' noncoding regions. Such IRES sequences are required for viral protein synthesis. In this study, a novel poliovirus was isolated whose genomic RNA contains two gross deletions removing approximately 100 nucleotides from the predicted IRES sequences within the 5' noncoding region. The deletions originated from previously in vivo-selected viral revertants displaying non-temperature-sensitive phenotypes. Each revertant had a different predicted stem-loop structure within the 5' noncoding region of their genomic RNAs deleted. The mutant poliovirus (Se1-5NC-delta DG) described in this study contains both stem-loop deletions in a single RNA genome, thereby creating a minimum IRES. Se1-5NC-delta DG exhibited slow growth and a pinpoint plaque phenotype following infection of HeLa cells, delayed onset of protein synthesis in vivo, and defective initiation during in vitro translation of the mutated poliovirus mRNAs. Interestingly, the peak levels of viral RNA synthesis in cells infected with Se1-5NC-delta DG occurred at slightly later times in infection than those achieved by wild-type poliovirus, but these mutant virus RNAs accumulated in the host cells during the late phases of virus infection. UV cross-linking assays with the 5' noncoding regions of wild-type and mutated RNAs were carried out in cytoplasmic extracts from HeLa cells and neuronal cells and in reticulocyte lysates to identify the cellular factors that interact with the putative IRES elements. The cellular proteins that were cross-linked to the minimum IRES may represent factors playing an essential role in internal translation initiation of poliovirus mRNAs.

Cross-Linking Reagents↗
PubMed1990

Effect of ring length and diameter on effective radial setting expansion.

It was previously demonstrated that flaring of MOD inlay castings was inversely proportional to the diameters of casting rings. The purpose of this study was (1) to determine if radial setting expansion of investment was primarily responsible for the inverse proportion and (2) to characterize further the fluid mechanics of setting expansion by determination of setting expansion in casting rings of different lengths and diameters. Eight sets of ten MOD inlay wax patterns with radiopaque markers at the axiogingival and axiopulpal junctions were individually invested in plastic casting rings in two groups: (A) 28 mm diameter and 30 mm, 32 mm, 34 mm, and 42 mm long; and (B) 28 mm, 40 mm, 51 mm, and 60 mm diameter and 34 mm long. All specimens were imaged (by xeroradiography) at specific intervals during the setting reaction; dimensions were measured on the images at each interval. In casting rings of different lengths, no significant differences (p greater than 0.05) were found in total effective setting expansion. Because setting expansion in the 28-mm-diameter rings was from 1.3% to 1.5% and diminished proportionately in rings of increasing diameter, setting expansion of investment appears to be the primary determinant of mold expansion. In casting rings of different diameters, significant differences (p less than 0.001) were found in total expansion in an apparent inverse proportion (p less than 0.001). Changes in dimension at intervals were strongly associated with time, and with time combined with diameter (p less than 0.001).

Dental Casting Investment↗
PubMed1988

Lymphocyte chimerism in a full allogeneic composite tissue (rat-limb) allograft model prolonged with cyclosporine.

LEW recipients of ACI vascularized hind limb allografts were analyzed for lymphoid chimerism by a complement-dependent cytotoxicity assay using antisera produced across this strain combination. In assessing the technique, two LEW recipients of sublethal irradiation (400 rad), ACI bone-marrow allografts, and CsA exhibited mixed lymphoid chimerism 23 days posttransplant. Short-term CsA-treated CTA recipients that were assayed at various times following transplantation and underwent subacute rejection did not demonstrate any significant mixed lymphoid chimerism. Long-term CsA-treated CTA recipients that were assayed at various times prior to 100 days posttransplant also did not demonstrate any significant mixed lymphoid chimerism. However, following extensive CTA survival (greater than 100 days) significant mixed donor-host lymphocyte chimerism became evident in the peripheral blood, and in one recipient a large quantity of donor bone marrow remained viable in the ACI limb allograft at necropsy (greater than 200 days posttransplant). The development of donor-host lymphocyte chimerism and a wasting syndrome that followed long-term CTA survival was suggestive of GVHD.

Animals↗
PubMedDate not supplied

Ring volume/ring liner ratio and effective setting expansion.

Effective radial setting expansion of wax patterns in a gypsum-bonded investment is influenced by many factors, especially by the diameter of the cylindrical casting ring. The hypothesis tested was that the ratio of the volume of the casting rings to the volume of the ring liner is a primary determinant of radial setting expansion. Mesio-occlusodistal inlay wax patterns were invested individually in plastic casting rings of different lengths and diameters and imaged using xeroradiography. Effective setting expansion was determined in 34-mm-long, 28-mm-diameter rings and used as a predictor of expansion in rings of different sizes. Experimental setting expansion results did not differ significantly from the predicted values.

Dental Casting Investment↗
PubMedDate not supplied

The relationship between the fit of MOD inlays and the storage time and conditions of investing.

It has been traditional either to cast invested wax patterns immediately after the investment has set or to store the invested patterns in a humidor for casting later. This study compared the fit of MOD inlays to parent dies after casting immediately following set of the investment, after casting 1 hour following the setting of the investment in air, storage in a humidor for 7 days, and after storage in air for 7 days. The only significant differences in fit were in the group stored in a humidor, and then only at the axiogingival junctions.

Analysis of Variance↗