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Biomedical subjects

H Nguyen

Publications and source records attributed to H Nguyen.

At least 127 records · Page 7Linked to original sources
PubMed1997

Ultrastructural and functional analyses of nephropathy in calmodulin-induced diabetic transgenic mice.

BACKGROUND: Previous animal models of diabetic nephropathy have used diabetic animals for which the underlying defect was either uncertain or the diabetes was induced by potentially specific toxins. In this report, we describe the renal abnormalities in a transgenic mouse model that develops early-onset diabetes due to overexpression of calmodulin in pancreatic beta cells. METHODS: Renal tissues were collected from normal and transgenic mice at 112, 182, and 300 days. These were prepared for light microscopic observation, stained with polyethylenimine (for anionic sites), or rendered acellular by detergent extraction prior to observation by transmission and scanning electron microscopy. Morphometric analysis of glomerular basement membrane thickness was carried out by the "orthogonal intercept" method. Twelve-hour urine samples of fed and fasting mice were collected for urine volume and glucose and protein analyses. Blood glucose, blood urea nitrogen, serum insulin, and creatinine were determined in 60-90-day-old and 255-day-old mice by established methods. RESULTS: Morphometric analyses revealed age-related and transgene-related increases in glomerular basement membrane thickness. A 22% increase in transgenic diabetics over controls was seen at 112 days of age that developed to increases of 43% and 37% at 182 and 300 days of age, respectively. Mesangial matrix area was also increased markedly in transgenic mice. Surprisingly, even in the oldest diabetic mice, there was no reduction in anionic sites. Moreover, despite an eightfold increase in urine volume, these mice did not become significantly proteinuric. CONCLUSIONS: These results indicate that proteinuria of diabetes may be delayed or prevented by maintenance of a normal complement of glomerular basement membrane anionic sites. They also demonstrate that transgenic mice can provide a valuable model for discriminating between different aspects of diabetic nephropathy.

Animals↗
PubMed1997

The effect of protein density of food on food intake and nutritional status of tumor-bearing rats.

Current clinical practice emphasizes increasing calorie and protein intake to abate the nutritional decline that frequently occurs in cancer patients. Using an animal model of tumor-induced anorexia, we found that increasing the protein density of food resulted in a net increase in protein intake, but a decrease in the food intake of both healthy and tumor-bearing animals. The increased protein intake did not affect the nutritional status of tumor-bearing animals as indicated by body weight or serum levels of total protein, insulin, or insulin-like growth factor 1. These data suggest that factors regulating feeding responses to increased protein density of food are intact in hypophagic tumor-bearing rats, and that increased protein intake does not influence plasma levels of hormones requisite for protein synthesis. These data may partially explain why interventions to improve the nutritional intake of cancer patients have marginal effects on body weight, accrual of lean body mass, or synthesis of visceral proteins.

Analysis of Variance↗
PubMed1997

Study of human isoursodeoxycholic acid metabolism.

BACKGROUND/AIMS: The aim of this study was to examine the metabolism of isoursodeoxycholic acid (isoUDCA) in humans. METHODS: IsoUDCA was synthesized of >99% purity and administered orally for 1 week, 3 x 250 mg/day, to six healthy male subjects. Bile acids were extracted from duodenal bile, serum, and 24-h urine samples collected before and at the end of the study period, separated into groups of conjugates, and analyzed by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. RESULTS: IsoUDCA was tolerated without any side effect. Liver function tests did not change. Bile acid concentrations (mean+/-SEM) increased from 11.9+/-1.87 to 15.3+/-1.37 mmol/l in bile (n.s.), and from 3.4+/-0.10 to 6.8+/-0.43 micromol/l in serum (p<0.05). Urinary excretion of bile acids increased from 5.3+/-0.29 to 82.2+/-7.84 micromol/24 h (p<0.01). All changes were due to significant increases of isoUDCA and UDCA in bile, serum and urine, and of 3-dehydro-UDCA, the 3-oxo intermediate of isomerization, in bile and in serum. The relative enrichments of isoUDCA, UDCA, and 3-dehydro-UDCA, were: in bile, 2.2%, 25.7%, and 0.7%; in serum, 24.7%, 23.5%, and 6.1%; and in urine, 83.7%, 2.0%, and 2.4%. Whereas 78% of serum isoUDCA was unconjugated, 93-94% of biliary and urinary isoUDCA was conjugated with N-acetylglucosamine. CONCLUSIONS: This study indicates good tolerance and significant intestinal absorption of orally administered isoUDCA. IsoUDCA is extensively isomerized, probably both by intestinal and hepatic enzymes to yield UDCA which became the major biliary compound. In vitro, using the human hepatoblastoma cell line Hep G2, isoUDCA was found to be cytoprotective towards ethanol-induced cell injuries.

Adult↗
PubMed1997

TIMP expression in toxic and cholestatic liver injury in rat.

BACKGROUND/AIMS: Hepatic fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. Recent evidence suggests that besides their increased synthesis, inhibition of matrix degradation plays a significant role. ECM degradation occurs via metalloproteinases which are inhibited in situ by specific tissue inhibitors of metalloproteinases (TIMPs). The aim of our studies was to determine the expression of TIMPs during toxic liver injury and cholestatic liver injury leading to fibrosis. METHODS: We examined the expression of TIMP-1, -2 and -3 in two different rat models for liver injury (intraperitoneal CCl4 injection and bile duct ligation) by Northern blot analysis and in situ hybridization. For comparison, the mRNA expression of the acute phase protein haptoglobin was measured. RESULTS: TIMP-1 was increased during the early phase of toxic liver injury and in cholestasis. Its expression occurred predominantly in areas of inflammation, in hepatocytes, and in mesenchymal and endothelial cells. There was a slight upregulation of TIMP-2 expression during cholestasis. TIMP-3 was not detected at all. CONCLUSIONS: Our results emphasize an involvement of TIMP-1 in matrix homeostasis, indicating its possible participation in liver fibrosis.

Animals↗
PubMed1997

The growing family of interferon regulatory factors.

Interferons (IFN) exert their multiple biological effects through the induction of expression of over 30 genes encoding proteins with antiviral, antiproliferative and immunomodulatory functions. Among the many IFN-inducible proteins are the Interferon Regulatory Factors (IRFs), a family of transcription regulators, originally consisting of the well-characterized IRF-1 and IRF-2 proteins; the family has now expanded to over 10 members and is still growing. The present review provides a detailed description of recently characterized IRF family members. Studies analyzing IRF-expressing cell lines and IRF knockout mice reveal that each member of the IRF family exerts distinct roles in biological processes such as pathogen response, cytokine signalling, cell growth regulation and hematopoietic development. Understanding the molecular mechanisms by which the IRFs affect these important cellular events and IFN expression will contribute to a greater understanding of events leading to various viral, immune and malignant disease states and will suggest novel strategies for antiviral and immune modulatory therapy.

Amino Acid Sequence↗
PubMed1997

Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal antibody targeting disialoganglioside in non-human primates.

Tumors metastatic to the leptomeninges are often incurable despite current aggressive treatment modalities. Regional therapy by intrathecal administration of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in the central nervous system is identical between humans and cynomolgus monkeys. We studied the pharmacokinetics and the acute and subacute toxicities of intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All animals remained clinically stable. Toxicities included weight loss, fever and CSF leukocytosis. One animal developed a left-sided hemiparesis following his seventh injection, presumably due to a local drug accumulation in the setting of an intermittently patent catheter. The estimated radiation dose to the CSF was 19-48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed chronic reactive changes adjacent to the region of catheter placement and a focal vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse antibody titers were less than 10 per cent of those in the serum. In contrast to the CSF radioactivity clearance which was similar in all animals, blood clearance was substantially accelerated in 3F8-immunized animals versus controls. Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean 3.5). We conclude that intraventricular administration of 131I-3F8 in primates is tolerable. It can deliver very high doses of radiation to the CSF space with minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates the clearance of 131I-3F8 in blood and may improve the therapeutic index.

Animals↗
PubMed1997

Efficient in vivo delivery of DNA to pulmonary cells using the novel lipid EDMPC.

We compared the efficacy of gene transfer in vitro and in vivo using various formulations of DNA-lipid complexes based on the novel cationic lipid EDMPC (1,2-dimyristoylsn-glycero-3-ethylphosphocholine, chloride salt). In vitro studies analyzed delivery of marker genes to four established cell lines, including two of pulmonary origin. The in vivo analysis used intralobar delivery of marker genes and CFTR to mice and rats. We observed a lack of positive correlation between those DNA-EDMPC formulations that delivered DNA most efficiently in vitro and those that worked best in vivo. Intralobar DNA delivery to rodents mediated by EDMPC was efficient. The high level of gene delivery by DNA-EDMPC formulations demonstrates that efficient lipid-mediated gene transfer to the lung is possible.

Animals↗
PubMed1997

[Spontaneous portasystemic shunt in liver cirrhosis: imaging with color-coded duplex ultrasonography].

PURPOSE: To demonstrate the usefulness of B-scan ultrasonography and color Doppler ultrasonography (CCDS) in the diagnosis of lumbal and splenorenal collateral veins in patients with liver cirrhosis. METHOD: 46 patients with histologically proven liver cirrhosis were examined by means of B-scan ultrasonography. CCDS was used to demonstrate the vascular character of mass-like lesions or tortuous tubular structures. Esophageal varices were demonstrated in 23 (50%) and ascites in 6 patients (13%). RESULTS: In 5 out of 46 patients (10.9%) we demonstrated lumbal and splenorenal portosystemic venous collaterals by B-scan- and CCDS. In 2 patients localized venous collaterals were demonstrated. No ascites was found in patients with accessory portosystemic shunts. CCDS showed the patency of these spontaneous portosystemic shunts. CONCLUSION: In patients with chronic liver disease CCDS is a noninvasive method to demonstrate spontaneous portosystemic shunts due to portal hypertension. The method provides information concerning patency and flow direction of the collateral veins.

Collateral Circulation↗
PubMed1997

Varicella-zoster virus glycoprotein I is essential for growth of virus in Vero cells.

Varicella-zoster virus (VZV) encodes at least six glycoproteins. Glycoprotein I (gI), the product of open reading frame 67, is a 58- to 62-kDa glycoprotein found in VZV-infected cells. We constructed two VZV gI deletion mutants. Immunoprecipitation of VZV gE from infected cells indicated that cells infected with VZV deleted for gI expressed a gE that was larger (100 kDa) than that expressed in cells infected with the parental virus (98 kDa). Cell-associated or cell-free VZV deleted for gI grew to lower titers in melanoma cells than did parental VZV. While VZV deleted for gI replicated in other human cells, the mutant virus replicated to very low titers in primary guinea pig and monkey cells and did not replicate in Vero cells. When compared with the parental virus, rescued viruses, in which the gI deletion was restored with a wild-type allele, showed a similarly sized gE and comparable growth patterns in melanoma and Vero cells. VZV deleted for gI entered Vero cells; however, viral DNA synthesis was impaired in these cells. The VZV gI mutant was slightly impaired for adsorption to human cells. Thus, VZV gI is required for replication of the virus in Vero cells, for efficient replication of the virus in nonhuman cells, and for normal processing of gE.

Animals↗
PubMed1997

Satisfaction of Vietnamese patients and their families with refugee and mainstream mental health services.

OBJECTIVE: The study examined levels of satisfaction with mainstream mental health services and specialized mental health services for refugees among Vietnamese psychiatric patients and their relatives. Demographic, diagnostic, symptomatic, and service-related issues that might influence satisfaction were investigated. METHODS: Eighty-six Vietnamese patients were identified from case notes of mainstream inpatient services (N = 31), mainstream community services (N = 7), and a specialized refugee treatment unit (N = 48). During an interview, a scale measuring satisfaction with treatment as well as measures of anxiety, depression, and posttraumatic stress disorder was administered to them. A modified satisfaction scale was administered to 56 relatives. RESULTS: Patients and relatives were, on average, moderately satisfied with treatment. Patients expressed greater satisfaction with the specialized treatment unit for refugees than with mainstream services, a finding that was not influenced by diagnostic differences or symptom levels at the time patients responded. Further analyses controlling for multiple comparisons revealed that the extent of the information provided and the ease of negotiating changes in treatment were the most salient variables in distinguishing satisfaction levels across the two types of treatment centers. Patients' fluency in English and their relatives' level of education were inversely associated with satisfaction scores, tentatively suggesting that the greater the ability of patients and their families to evaluate services, the less likely they were to express satisfaction with treatment. CONCLUSIONS: Specialized mental health services for refugees may be more acceptable to refugee populations than their mainstream counterparts, perhaps because better communication with patients and their families is possible in the specialized services. Patients and families who are in a position to evaluate services fully are more likely to be critical of treatments offered.

Acculturation↗
PubMed1996

Growth pattern and clinical correlation of subcutaneously inoculated human primary acute leukemias in severe combined immunodeficiency mice.

We examined the ability of patient-derived human leukemic blasts to generate leukemic growth and dissemination in severe combined immunodeficiency (SCID) mice by subcutaneous inoculation without conditioning treatment or administration of growth-promoting cytokines. Additionally, we correlated the growth pattern with the clinical outcome of patients from whom the leukemic cells were derived. The leukemias displayed three distinct growth patterns, ie, either aggressive, indolent, or no tumor growth. Leukemic cells from 6 of 13 patients with acute myeloid leukemia (AML), 4 of 7 T-cell acute lymphoblastic leukemia (T-ALL), and 11 of 16 patients with B-lineage ALL grew as subcutaneous tumors, with a significant number subsequently disseminating into distant organs in SCID mice. Patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SCID mice had a relatively poor clinical outcome, whereas patients with AML and T- or B-lineage ALL whose leukemic blasts grew indolently or whose cells failed to induce growth had a more favorable clinical course. Our study has shown that the subcutaneous inoculation of patient-derived human leukemic cells in SCID mice can engraft and grow as subcutaneous tumors with subsequent dissemination to distant organs in a manner analogous to their pattern of growth in humans. Additionally, these data suggest a clinical correlation to the growth and dissemination of some leukemic subtypes that may represent not only an additional prognosticator for patient outcome, but also a vehicle for the study of the biologic behavior of human leukemias and the development of novel therapeutic strategies.

Acute Disease↗
PubMed1996

CD40-mediated stimulation contributes to lymphocyte proliferation, antibody production, eosinophilia, and mastocytosis during an in vivo type 2 response, but is not required for T cell IL-4 production.

CD40/CD40 ligand interactions are required for the development of T cell-dependent Ab responses in vivo. The role of these cell surface molecules in contributing to T cell cytokine production and the development of effector populations other than B cells and T cells is, however, less well defined. We have examined the in vivo effects of blocking CD40/CD40 ligand interactions on the type 2 mucosal immune response that follows oral inoculation of mice with the nematode parasite, Heligmosomoides polygyrus. Administration of anti-gp39 (CD40L) mAb (MR1) blocked H. polygyrus-induced elevations in serum IgG1 levels and inhibited elevations in blood eosinophils and mucosal mast cells at day 14 after inoculation. Anti-gp39 mAb markedly inhibited B cell blastogenesis 8 days after H. polygyrus inoculation but did not inhibit elevations in B cell class II MHC expression. Maximal elevations in B7-2 expression required signaling through both CD40 and the IL-4R. Elevations in T cell cytokine gene expression and elevations in the number of IL-4-secreting cells were unaffected by treatment with anti-gp39 mAb, although IL-4 production was inhibited by anti-IL-4R mAb. These results suggest that CD40/CD40L interactions are not required to activate T cells to produce cytokines but are required for the activation and proliferation of other effector cells associated with the type 2 response.

Animals↗
PubMed1996

[Lemierre's post-tonsillitis sepsis with meningitis and intravascular consumption coagulopathy as complication of infectious mononucleosis with pansinusitis].

HISTORY AND CLINICAL FINDINGS: 24 days after the onset of infectious mononucleosis, clinically and serologically confirmed, an otherwise healthy 18-year-old schoolboy developed a fulminant septicaemia with acute meningitis and loss of consciousness, consumptive coagulopathy and acute renal failure. INVESTIGATIONS: Computed tomography demonstrated pansinusitis. Lumbar puncture produced purulent cerebrospinal fluid with 11,500 cells/microliters, predominantly granulocytes, protein 205 mg/dl, glucose 19 mg/dl, indicating bacterial meningitis. The suspected diagnosis of posttonsillitis septicaemia (Lemierre's syndrome) was confirmed by repeated demonstration of fusiform gram-negative bacteria in anaerobic blood cultures, identified as Fusobacterium necrophorum. Anaerobic CSF culture grew Prevotella bivia of the Bacteroidaceae family. TREATMENT AND COURSE: Both the consumptive coagulopathy and the renal failure were successfully treated and the patient's condition stabilized. The sinuses were surgically drained under high doses of piperacillin/sulbactam and chloramphenicol. Despite the sensitivity of the cultured bacteria to the administered antibiotics the septic temperature continued, but disappeared within 4 days of metronidazole having been added. After 5 weeks of antibiotic treatment, three of them in an intensive care unit, the patient was discharged in good general condition. CONCLUSION: This case illustrates that severe septicaemia caused by rare bacteria may follow an attack of infectious mononucleosis which had taken an uncomplicated course.

Acute Kidney Injury↗
PubMed1996

The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase.

Although bisphosphonates have been shown to be potent inhibitors of osteoclast-mediated bone resorption in vivo and in vitro and are used as therapeutic agents in hyper-resorptive bone diseases such as Paget disease or hypercalcemia of malignancy, their exact biochemical target(s) and mode(s) of action are for the most part still unknown. The resorption of bone requires solubilization of the mineral component of the matrix, achieved by acidification of the resorbing compartment by a vacuolar-type proton ATPase (V-ATPase) present in the ruffled border membrane of osteoclasts. Since we have shown that the V-ATPase is inhibited by both ADP and phosphate, which share structural characteristics with bisphosphonates, we hypothesized that inhibition of the osteoclast V-ATPase could be one of the mechanism(s) by which bisphosphonates inhibit bone resorption. Pyrophosphate and the bisphosphonates etidronate, alendronate, and YM-175 inhibited proton transport in membrane vesicles derived from chicken kidney and osteoclasts but with very low potency (IC50 > or = 5 mM). In contrast, the ability of tiludronate to inhibit proton transport was 5-fold higher in kidney-derived vesicles (IC50 = 1.1 mM) and 10,000-fold higher in vesicles derived from osteoclasts (IC50 = 466 nM). Tiludronate also potently inhibited proton transport in yeast microsomal preparations (IC50 = 3.5 microM) and inhibited the activity of purified yeast V-ATPase. The inhibition of the osteoclast V-ATPase-mediated proton transport by tiludronate was rapid, pH-dependent, and reversible. No change in membrane vesicle permeability to protons was detected. The inhibition was noncompetitive with respect to ATP, and tiludronate did not protect the pump from inactivation by N-ethylmaleimide, strongly suggesting that tiludronate does not bind to the catalytic site of the enzyme. It is concluded that tiludronate is a significantly more potent inhibitor of V-ATPase than other bisphosphonates and that it has a significant degree of selectivity for the avian osteoclast V-ATPase relative to the avian kidney V-ATPase.

Alendronate↗