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Biomedical subjects

J H Nguyen

Publications and source records attributed to J H Nguyen.

At least 19 recordsLinked to original sources

Review of 31 cases of morphologic hepatitis in liver transplant patients not related to disease recurrence.

AIMS: We examined the clinical and pathologic features of morphologic hepatitis occurring after liver transplantation (LT) that is unrelated to disease recurrence. METHODS: Between February 1998 and December 2003, 704 primary LTs were performed at our center. Patients transplanted for diagnoses with low risk of disease recurrence were considered for our study (n = 282). Those with hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those with morphologic hepatitis comprised our case series and had medical records reviewed for clinical associations, duration, and outcome. RESULTS: Thirty-one cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13), steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2), and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8 months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and moderate in 12. Associated conditions were identified in 19 patients (57%) with 3 categories being identified: probable drug toxicity (n = 7), systemic infection (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the index biopsy, 10 cases had resolution and 15 cases had persistence of the infiltrate. One patient had evidence of de novo HBV infection. CONCLUSIONS: Morphologic hepatitis occurred in 11% of patients at low risk for disease recurrence. Associated conditions could be grouped into three categories: drug toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases did not appear to progress or improved over time, with no allograft loss occurring as a result of chronic hepatitis.

Biopsy↗

Clinicopathological review of 18 cases of liver allografts lost due to bile duct necrosis.

Clinical, radiographic, and pathological features of 18 patients with biliary necrosis in their explanted liver allografts were reviewed. Twelve patients were men and ages ranged from 27 to 72 years. Indications for initial liver transplant (LT) were viral hepatitis (n = 7), steatohepatitic cirrhosis (n = 3), cryptogenic cirrhosis (n = 3), secondary sclerosing cholangitis (n = 2), primary sclerosing cholangitis (n = 1), biliary atresia (n = 1), and nodular regenerative hyperplasia (n = 1). Donor age ranged from 16 to 75 years. Duct-to-duct biliary anastomoses were fashioned in 13 cases; warm and cold ischemia times were not significantly different from general LT population. Seventeen allograft biopsies after recirculation had no significant findings. Post-LT, clinical and radiographic evaluation indicated biliary strictures (n = 7), bile leak (n = 7), intrahepatic abscess (n = 1), and duodenal perforation (n = 1). Radiographic vascular studies suggested hepatic arterial thrombosis or stenosis in 11 cases. Biopsies prior to retransplantation were performed on 17 patients and showed acute rejection (n = 10), biliary outflow impairment (n = 4), normal histology (n = 2), and centrilobular necrosis (n = 1). Retransplantation was performed 14 to 334 days after initial LT. Pathological examination of explants revealed perihilar duct necrosis in all cases, with bacterial colonies (n = 10) and fungal organisms (n = 2). Arterial thrombi were seen in 10 cases, and two had prominent arteriosclerosis. Infarction and centrilobular necrosis were seen in 9 and 13 cases, respectively. Four explants showed features of biliary outflow impairment. Twelve patients were alive 6 to 18 months following retransplantation. We conclude that post-LT biliary necrosis is associated with ischemia, and such a complication is rarely evident in allograft biopsies. Biliary and vascular imaging studies are essential in evaluating patients for this complication.

Adolescent↗

Myofibrosarcoma of the adrenal gland.

Adrenal masses have varying presentations. Most commonly, adrenal masses are discovered incidentally on CT or MRI during an evaluation for an unrelated complaint. Although the majority of these are nonfunctional cortical adenomas, hormonally active tumors and adrenocortical carcinoma must also be considered in the differential diagnosis. Rarely, retroperitoneal tumors may mimic an adrenal mass. We report a case of a 49-year-old man with anemia and weight loss who was found to have a large retroperitoneal mass arising from the adrenal gland. Surgical treatment involved en bloc resection of the right kidney, adrenal gland, segments 7 and 8 of the liver, and a portion of the right hemidiaphragm. Final pathology revealed a low-grade myofibrosarcoma. We believe that this is the first case report of a myofibrosarcoma of the adrenal gland. Myofibrosarcomas are rare malignant tumors composed of myofibroblasts that arise from the deep soft tissues. These tumors have a predilection for the head and neck, trunk, or extremities. Myofibrosarcomas can be differentiated from other sarcomas by immunohistochemical staining and pathologic features. We will briefly discuss the workup of an adrenal mass and focus on the diagnosis of myofibrosarcoma.

Adrenal Gland Neoplasms↗

Dissociation of CH4 at high pressures and temperatures: diamond formation in giant planet interiors?

Experiments using laser-heated diamond anvil cells show that methane (CH4) breaks down to form diamond at pressures between 10 and 50 gigapascals and temperatures of about 2000 to 3000 kelvin. Infrared absorption and Raman spectroscopy, along with x-ray diffraction, indicate the presence of polymeric hydrocarbons in addition to the diamond, which is in agreement with theoretical predictions. Dissociation of CH4 at high pressures and temperatures can influence the energy budgets of planets containing substantial amounts of CH4, water, and ammonia, such as Uranus and Neptune.

Diamond↗

Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements.

The translation of picornavirus genomic RNAs occurs by a cap-independent mechanism that requires the formation of specific ribonucleoprotein complexes involving host cell factors and highly structured regions of picornavirus 5' noncoding regions known as internal ribosome entry sites (IRES). Although a number of cellular proteins have been shown to be involved in picornavirus RNA translation, the precise role of these factors in picornavirus internal ribosome entry is not understood. In this report, we provide evidence for the existence of distinct mechanisms for the internal initiation of translation between type I and type II picornavirus IRES elements. In vitro translation reactions were conducted in HeLa cell cytoplasmic translation extracts that were depleted of the cellular protein, poly(rC) binding protein 2 (PCBP2). Upon depletion of PCBP2, these extracts possessed a significantly diminished capacity to translate reporter RNAs containing the type I IRES elements of poliovirus, coxsackievirus, or human rhinovirus linked to luciferase; however, the addition of recombinant PCBP2 could reconstitute translation. Furthermore, RNA electrophoretic mobility-shift analysis demonstrated specific interactions between PCBP2 and both type I and type II picornavirus IRES elements; however, the translation of reporter RNAs containing the type II IRES elements of encephalomyocarditis virus and foot-and-mouth disease virus was not PCBP2 dependent. These data demonstrate that PCBP2 is essential for the internal initiation of translation on picornavirus type I IRES elements but is dispensable for translation directed by the structurally distinct type II elements.

5' Untranslated Regions↗

Success with intestinal failure: from adaptation to transplantation.

Intestinal failure can result from large resections of small intestine (short bowel syndrome) and from failure of normal intestinal motility. The medical management of short bowel syndrome centers around appropriate diet and use of specific medications including experimental trophic factors. Enteral tubes and prokinetic medications can be successfully used to treat patients with intestinal failure as a result of abnormal intestinal motility. Small bowel transplantation may be a treatment option in certain patients with intestinal failure. This article reviews the management of intestinal failure with a recent update on small bowel transplantation.

Adaptation, Physiological↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Effect of denture wax-pattern position on radial setting expansion.

Th dynamics of the setting expansion of gypsum-bonded investment is complicated by many variables and not well understood. The purposes of this study were to examine the fluid mechanics of the flow of investment during setting and to determine if the presence of wax patterns influences effective setting expansion. Mesial-occlusal-distal (MOD) inlay wax patterns were invested at six different radial positions and four different axial positions in plastics casting rings. Total expansion was determined by using xeroradiography. Combined results of radial expansion data at different axial and radial locations within casting rings suggest that expansion of gypsum-bonded investment may represent a variant of the laminar flow of a viscous fluid.

Dental Bonding↗

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↗

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↗

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↗