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Biomedical subjects

L T Nguyen

Publications and source records attributed to L T Nguyen.

At least 37 records · Page 2Linked to original sources

Clinical characteristics and outcome of patients with invasive pneumococcal disease, Puy-de-Dôme, France, 1994-1998.

A surveillance program for invasive pneumococcal disease was undertaken in Puyde-Dĵme, an administrative district of the region Auvergne in France, from 1 January 1994 to 31 December 1998. A total of 214 cases were identified. The annual incidence of invasive pneumococcal disease increased (P=0.04) from 5.5 in 1994 to 9.3 cases per 10(5) person-years in 1998. The highest incidences were for children <2 years of age (59.2 cases per 10(5) person-years) and for adults > or = 65 years (18 cases per 10(5) person-years). Clinical diagnoses, available in 200 patients, included acute pneumonia (62%), meningitis (10%), sepsis without focus (20%), and others (8%). The most frequent chronic medical conditions of the patients included smoking, alcoholism, cardiovascular and pulmonary diseases, and malignancies. Thirty-one percent of the isolates were nonsusceptible to penicillin. Penicillin resistance (MIC > or = 0.1 mg/l) was more frequent (P=0.02) in cancer patients. The overall case-fatality rate was 21.5%. Risk factors for death were age, sex, and underlying diseases of the patients, along with the severity of illness. These population-based findings should convince clinicians to offer pneumococcal vaccine to patients at high risk for invasive pneumococcal disease, thereby increasing vaccination coverage levels in France.

Adolescent↗

Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway.

Using a combination of local gene delivery and tolerizing DNA vaccination, we demonstrate that codelivery of the interleukin-4 (IL-4) gene and a DNA vaccine encoding the self-peptide proteolipid protein 139-151 (PLP139-151) provides protective immunity against experimental autoimmune encephalomyelitis (EAE). We provide evidence for a mechanism whereby IL-4 expressed from the naked DNA is secreted and acts locally on autoreactive T cells via activation of STAT6 to shift their cytokine profile to T helper 2. We also show that DNA vaccines can be used to reverse established EAE by covaccination with the genes for myelin oligodendrocyte glycoprotein and IL-4. This treatment strategy combines the antigen-specific effects of DNA vaccination and the beneficial effects of local gene delivery.

Animals↗

Congenital thrombocytopenia and radio-ulnar synostosis: a new familial syndrome.

The association of bone marrow failure and skeletal defects has been frequently noted, however, the genetic basis for most of these syndromes remains unclear. We describe a previously uncharacterized autosomal dominant syndrome of amegakaryocytic thrombocytopenia associated with radial-ulnar synostosis. The clinical features of this syndrome appear to be distinct from other similar conditions, including Fanconi's anaemia and thrombocytopenia-absent radii (TAR). The physical findings at diagnosis and clinical management of each case are detailed, as well as a discussion of this disorder in the context of other syndromes in which marrow failure and skeletal defects are prominent features. We also review recent developments in molecular genetics that may provide important clues to the underlying aetiology of this condition.

Bone Marrow Cells↗

Clinical versus sonographic evaluation of acute appendicitis in children: a comparison of patient characteristics and outcomes.

PURPOSE: Abdominal sonography has gained popularity in establishing the diagnosis of appendicitis in children with equivocal clinical presentations. However, no clear outcome benefits have been demonstrated to date. The authors conducted a retrospective study to compare the characteristics and outcomes of patients undergoing appendectomy after clinical evaluation only with those undergoing the procedure after sonography. METHODS: The charts of 454 consecutive patients undergoing appendectomy for acute appendicitis between January 1, 1998 and December 4, 1999 were reviewed. Patients operated on after clinical evaluation only were compared with patients operated on after abdominal sonography. RESULTS: Forty-two percent of patients (n = 191) constituted the sonography group. When compared with the clinical group, these patients had higher prevalence of female gender (52% v 38%; P =.004), longer symptom duration (2.2 +/- 2.5 v 1.6 +/- 1.6 days; P =.003), higher incidence of preoperative in-patient observation (19% v 4%; P <.001), longer duration between evaluation and operation (8.0 +/- 3.9 v 4.9 +/- 2.9 hours; P <.001), higher incidence of normal appendices on pathologic examination (13% v 6%; P =.006), and higher incidence of postoperative abscesses or phlegmons (4.4% v 1.2%; P =.04). The groups did not differ significantly in age, hospital stay, incidence of complicated appendicitis, or incidence of wound infection. CONCLUSIONS: Patients undergoing sonography before appendectomy have a longer delay before operation, a higher rate of misdiagnosis, and more postoperative complications. Limiting sonography to truly equivocal cases and using it early in the diagnostic workup may improve outcomes in this group of patients.

Abscess↗

Laparoscopic excision of subdiaphragmatic epidermoid cyst: a case report.

Retroperitoneal epidermoid cysts are rare. The authors report a case of an 11-year-old boy with an asymptomatic subdiaphragmatic cyst, which was found incidentally during an investigation for hypertension. At laparoscopy, the cyst was densely adherent to the diaphragm, resulting in a pneumothorax during dissection. Nevertheless, the excision and the diaphragmatic repair could be completed laparoscopically without complication. Microscopic examination showed an epidermoid cyst. No similar case has been reported in the literature.

Child↗

The use of a computer-assisted image-guided system (InstaTrak) in orbital surgery.

PURPOSE: To assess the usefulness of a computer-assisted image-guided system (CAIGS) as an intraoperative anatomical guide in performing orbital surgery. METHODS: Noncomparative interventional case series of 30 consecutive orbital procedures performed by one surgeon (J.G.C.) using the CAIGS (InstaTrak) for intraoperative anatomical guidance. RESULTS: The series consisted of 8 cases of orbital decompression, 8 cases of orbital fracture, 11 cases of tumor excision, 2 cases of orbital reconstruction for severe enophthalmos, and 1 case of drainage of an orbital abscess. The CAIGS (InstaTrak) was useful in providing adjunctive intraoperative guidance in all 30 orbital cases. CONCLUSION: The CAIGS (InstaTrak) system is a useful adjunctive tool in providing intraoperative anatomic guidance in a consecutive series of varied orbital operations.

Adult↗

Comparative sensitivity of embryo-larval toxicity assays with African catfish (Clarias gariepinus) and zebra fish (Danio rerio).

Embryo-larval toxicity tests with the African catfish (Clarias gariepinus) were conducted with five chemicals (Cr, Cd, Zn, NaPCP and malathion) and three environmental samples. The sensitivity of the 5-day assay was compared to that of the 12-day embryo-larval toxicity tests with the zebra fish (Danio rerio). The ratios of the C. gariepinus and D. rerio LC50 values ranged from 0.4 for Cr to 8.9 for Zn. The ratios of subchronic values ranged from 0.25 for NaPCP to 3.1 for Cd indicating a more comparable sensitivity of the two species. For the three sediment pore waters, the ratios were 0.6, 1.1, and 2.4 and the subchronic values were identical for the two species. The results suggest that, considering the short-test duration and its sensitivity, the 5-day embryo-larval tests with C. gariepinus may be a potential alternative for short-term embryo-larval toxicity testing with fish.

Animals↗

Negative regulation of T cell proliferation and interleukin 2 production by the serine threonine kinase GSK-3.

Glycogen synthase kinase (GSK)-3 is a protein serine/threonine kinase that regulates differentiation and cell fate in a variety of organisms. This study examined the role of GSK-3 in antigen-specific T cell responses. Using resting T cells from P14 T cell receptor (TCR)-transgenic mice (specific for the lymphocytic choriomeningitis virus and H-2D(b)), we demonstrated that GSK-3beta was inactivated by serine phosphorylation after viral peptide-specific stimulation in vitro. To further investigate the role of GSK-3, we have generated a retroviral vector that expresses a constitutively active form of GSK-3beta that has an alanine substitution at the regulatory amino acid, serine 9 (GSK-3betaA9). Retroviral transduction of P14 TCR-transgenic bone marrow stem cells, followed by reconstitution, led to the expression of GSK-3betaA9 in bone marrow chimeric mice. T cells from chimeric mice demonstrate a reduction in proliferation and interleukin (IL)-2 production. In contrast, in vitro assays done in the presence of the GSK-3 inhibitor lithium led to dramatically prolonged T cell proliferation and increased IL-2 production. Furthermore, in the presence of lithium, we show that nuclear factor of activated T cells (NF-AT)c remains in the nucleus after antigen-specific stimulation of T cells. Together, these data demonstrate that GSK-3 negatively regulates the duration of T cell responses.

3T3 Cells↗

Role of antigen-presenting cells in mediating tolerance and autoimmunity.

The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic beta-islet cells together with T cells expressing an LCMV-gp-specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.

Animals↗

Localization of choline acetyltransferase in the developing and adult turtle retinas.

Acetylcholine has important epigenetic roles in the developing retina. In this study, cells that expressed choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine, were investigated in embryonic, postnatal, and adult turtle retinas by using immunofluorescence histochemistry. ChAT was present at stage 15 (S15) in cells near the vitreal surface. With the formation of the inner plexiform layer (IPL) at S18, ChAT-immunoreactive (-IR) cells were located in the inner nuclear layer (INL) and the ganglion cell layer (GCL). In the INL, presumed starburst amacrine cells were homogenous in appearance and formed a single row next to the IPL: This pattern was conserved until adulthood. In the GCL, however, there were multiple rows of ChAT-IR cells early in development, and this high density of labeled cells continued during the embryonic stages, until around birth. The high density of ChAT-IR cells in the GCL was due in part to a population of cells that expressed ChAT transiently. In postnatal stages and adult retinas, the presumed starburst amacrine ChAT-IR cells formed two mirror-like rows of homogenous cells on both borders of the IPL. Two cholinergic dendritic strata that were continuous with these cells were observed as early as S18, and their depths in the IPL were relatively stable throughout development. A third population of ChAT-IR cells was observed toward the middle of the INL around S25 and persisted into adulthood. Finally, cells in the outer nuclear layer (ONL) were ChAT-IR during the embryonic stages, were less immunoreactive during the postnatal stages, and were not immunoreactive in the adult retinas.

Animals↗

Colocalization of choline acetyltransferase and gamma-aminobutyric acid in the developing and adult turtle retinas.

Acetylcholine and gamma -aminobutyric acid (GABA) are putative neurotransmitters in the adult vertebrate retina. In this study, cells that coexpress choline acetyltransferase (ChAT) and GABA or glutamic acid decarboxylase (GAD) were investigated in turtle retinas from stage 14 (S14) to adulthood by using a double-labeling immunofluorescence technique. ChAT immunoreactivity was observed at S15 and included not only the presumptive starburst cholinergic amacrine cells but also a population in the ganglion cell layer (GCL) that expressed ChAT transiently during the embryonic stages (see the accompanying paper: Nguyen et al. [2000] J. Comp. Neurol. 420:512-526).

Aging↗

Cross-correlation for flow cytometric histogram background subtractions.

Background subtraction is a widely encountered problem in flow cytometry applications for which the currently available analysis techniques are unsatisfactory. The 99% division line method, also referred to as the threshold or marker method, is widely used because it is computationally simple but it has poor accuracy and tends to underestimate the percentage of positive cells when there is overlap between histograms. Model-based approaches are preferred when there are overlapping peaks, but these methods require curve fitting and strong assumptions regarding the shape of the underlying distributions. This report assesses a mathematically rigorous, computationally facile, non-parametric technique called cross correlation for the background subtraction problem. A metric, positivity, derived from cross correlation is shown to overcome the disadvantages of both the 99% division line and model-based methods without compromise.

Flow Cytometry↗

Links between Fer tyrosine kinase expression levels and prostate cell proliferation.

In our cloning strategy to identify tyrosine kinases implicated in the regulation of prostate growth, the dog fer cDNA was obtained and shown to be highly homologous to known fer cDNAs. Using a polyclonal Fer antibody directed against a C-terminal peptide, we studied its associations with cortactin, beta-catenin and p120Cas in human prostate carcinoma PC-3 cells. In contrast to previous reports, no interactions were observed. To assess its functional role, fer cDNA constructs were transfected in PC-3 cells. Antisense clones exhibiting a marked diminution of Fer expression had a reduced growth rate (doubling time of 29 vs. 42 h) and were unable to form colonies in soft agar. In agreement with these results, Fer protein expression was linked to human prostatic proliferative diseases, with enhanced levels in extracts from cancer tissues as compared to those from normal and hyperplastic ones, and was also expressed in the human prostate carcinoma cell lines DU145 and LNCaP. In the dog model, Fer expression was up-regulated in dividing versus resting prostate epithelial cells in vitro, and also in vivo when basal cell hyperplasia and metaplasia was induced by estrogen after castration. Minimal effects were observed when renewing the luminal epithelium with androgens. Taken together, these results show that Fer expression is associated with prostate cell proliferation and enhanced in prostate cancer.

Amino Acid Sequence↗

TNF receptor 1 (TNFR1) and CD95 are not required for T cell deletion after virus infection but contribute to peptide-induced deletion under limited conditions.

Deletion of mature T cells maintains cellular homeostasis and is involved in the maintenance of self tolerance to some peripheral self antigens. Previous studies have presented conflicting evidence for a role of the tumor necrosis factor receptor (TNFR) family member CD95 (Fas) in peripheral T cell deletion using CD95-deficient mice. To evaluate cooperation between CD95 and another TNFR family molecule, TNFR1, we generated mice deficient for both CD95 and TNFR1. We showed that TNFR1 and CD95 do not contribute to the decline of antigen-specific cytotoxic T lymphocytes after virus infection. Using TNFR1 / CD95-deficient mice expressing the P14 TCR specific for a lymphocytic choriomeningitis virus-derived peptide (p33) we showed that deletion of p33-specific CD8(+) T cells following high dose p33 administration is also normal. However, in non-TCR-transgenic TNFR1 / CD95-deficient mice treated with the same p33 regimen, tolerance induction was defective. These data indicate that TNFR1 and CD95 are dispensable for deletion of antigen-specific T cells after viral infection. However, under certain conditions, both TNFR1 and CD95 appear to cooperate in CD8(+) T cell deletion.

Animals↗

Intracellular calcium during fatigue of cane toad skeletal muscle in the absence of glucose.

Mechanisms of fatigue were studied in single muscle fibres of the cane toad (Bufo marinus) in which force, intracellular calcium ([Ca2+]i), [Mg2+]i, glycogen and the rapidly releasable Ca2+ from the sarcoplasmic reticulum (SR) were measured. Fatigue was produced by repeated tetani continued until force had fallen to 50%. Two patterns of fatigue in the absence of glucose were studied. In the first fatigue run force fell to 50% in 8-10 min. Fatigue runs were then repeated until force fell to 50% in < 3 min in the final fatigue run. Addition of extracellular glucose after the final fatigue run prolonged a subsequent fatigue run. In the first fatigue run peak tetanic [Ca2+]i initially increased and then declined and at the time when force had fallen to 50% tetanic [Ca2+]i was 54+/-5% of initial value. In the final fatigue run force and peak tetanic [Ca2+]i declined more rapidly but to the same level as in first fatigue runs. At the end of the first fatigue run, the rapidly releasable SR Ca2+ store fell to 46+/-6% of the pre-fatigue value. At the end of the final fatigue run the rapidly releasable SR Ca2+ store was 109+/-16% of the pre-fatigue value. In unstimulated fibres the nonwashable glycogen content was 176+/-30 mmol glycosyl units/l fibre. After one fatigue run the glycogen content was 117+/-17 mmol glycosyl units/l fibre; at the end of the final fatigue run the glycogen content was reduced to 85+/-9 mmol glycosyl units/l fibre. [Mg2+]i did not change significantly at the end of fatigue in either the first or the final fatigue run suggesting that globally-averaged ATP does not decline substantially in either pattern of fatigue. These results suggest that different mechanisms are involved in the decline of tetanic [Ca2+]i in first compared to final fatigue runs. The SR Ca2+ store is reduced in first fatigue runs; this is not the case for the final fatigue run which is associated with a decline in glycogen and possibly related to either a non-metabolic effect of glycogen or a spatially-localised metabolic decline.

Animals↗

Delayed presentation of a congenital recto-vaginal fistula associated with a recto-sigmoid tubular duplication and spinal cord and vertebral anomalies.

Tubular duplication of the recto-sigmoid colon is a rare entity. Associated anomalies including fistulae to the genitourinary tract may be found. A baby girl was found to have duplication of the recto-sigmoid colon, anomalies of sacral vertebra from S1 to S5, and solitary right kidney. The septum of this duplication was divided using staplers. Because of a history of stool coming from the vagina, a meticulous examination perioperatively was performed, but no fistula could be found. Further extensive investigation failed to show any fistula. At the age of 10 she was operated on for a tethered cord. At age 14, she experienced passage of a small amount of liquid stool per vaginum. A recto-vaginal fistula was found. Via a posterior sagittal incision, the fistula was closed by a transrectal approach. She remained asymptomatic for 16 months until the fistula recurred. Using a perineal approach, a very short fistula between the vagina and the rectum was closed. The closure was reinforced by a vaginal flap. Four months later, she remains without signs of recurrence.

Abnormalities, Multiple↗

Should malrotation in children be treated differently according to age?

PURPOSE: The aim of this study was to better define the mode of presentation, rate of volvulus, and surgical findings in children younger than 2 versus older than 2 years of age with malrotation. METHODS: The authors reviewed the charts of all patients with malrotation admitted to their hospital between January 1980 and December 1998, excluding patients having malrotation as a secondary finding. RESULTS: An upper gastrointestinal series was done in 90 patients (6% falsely negative) and a barium enema in 20 patients (40% read as normal). Fifty-eight patients had 114 associated congenital anomalies. Volvulus was found at the time of surgery in 28 patients, 5 of whom were older than 2 years. Three presented with acute symptoms and 2 with chronic symptoms. Surgery was performed by laparotomy in 103 patients and by laparoscopy in 3. Mean length of stay was 13.6 days. Mean follow-up was 19 months. Death occurred in 4 patients; postoperative bowel obstruction was seen in 3 patients (only 1 required surgery). CONCLUSIONS: Children with malrotation who are older than 2 years old have a significant risk of volvulus that is difficult to predict radiologically. They require surgical attention even if asymptomatic. Laparoscopy allows evaluation of the base of the mesentery and completion of the Ladd's procedure.

Age Factors↗