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Biomedical subjects

T Nguyen

Publications and source records attributed to T Nguyen.

428 records · Page 24Linked to original sources
PubMedDate not supplied

In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: feasibility and short-term follow-up.

In utero allotransplantation of fetal hepatocytes into a preimmune fetus could be used in early treatment of many inherited hepatic metabolic diseases. This study was designed to assess the tolerance to hepatocyte transplantation and to test the feasability and toxicity of such an injection in a primate model. Fetal hepatocytes were obtained from two 120-day-old Macaca mulatta fetuses and cryopreserved. They were thawed, cultured in vitro, and transduced with a recombinant retrovirus expressing beta-galactosidase. Transduction efficiency was 75-85%. Three unrelated fetuses (90, 100, and 104 days old) were each given 1-2 x 10(7) transduced cells via the umbilical vein. This caused vasospasm and severe bradycardia. Two fetuses died in the 48 hours after transplantation; the third survived and was killed at the end of gestation. No evidence of the infused cells was found. Three fetuses (90 days old) were, therefore, given 3-4 10(7) hepatocytes by direct intrahepatic injection. All the fetuses survived without side effect. Donor cells were not apparent from histochemical staining and PCR reactions. There was no evidence of inflammatory reaction. These findings indicate that the protocole could be improved by increasing the number of transplanted cells and using specific hepatic promoters in the retroviral vectors to achieve an effective postnatal chimerism.

Animals↗
PubMedDate not supplied

Functional interleukin-4 receptor and interleukin-2 receptor common gamma chain in human gastric carcinoma: a possible mechanism for cytokine-based therapy.

Interleukin (IL)-2 and IL-4 play a critical role in the regulation of the immune response. Yet both of the receptors for these cytokines have been found on nonhematopoietic cells, including human gastric carcinoma cell lines and tissue specimens. IL-4 causes G1 phase cell cycle arrest of gastric carcinoma; the effect directly correlates with the expression of IL-4 receptor (IL-4R) and is seen within 48 hours after treatment. Cells lacking IL-4R are unaffected by IL-4. We examined signal transduction pathways employed by IL-4 that may account for cell cycle arrest of an established human gastric carcinoma cell line, CRL 1739. Western blot analysis was performed on CRL 1739 cultured in the presence of IL-4 (500 U/ml). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine mono-clonal antibodies to specific intracellular proteins. Western blotting of CRL 1739 with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kDa and 65 kDa) phosphoproteins seen only in IL-4-treated CRL 1739. Immunoprecipitation and blotting of CRL 1739 with specific secondary antibodies demonstrated that the 140 kDa phosphoprotein was IL-4R", the 65kDa phosphoprotein was IL-2Rgc, the 130 kDa phosphoprotein was Janus kinase (JAK1), and the 116 kDa phosphoprotein was JAK3. Reverse transcription-polymerase chain reaction with specific primers demonstrated that multiple human gastric tumor specimens expressed IL-4R" and IL-2Rgc but did not express the leukocyte marker CD45. These results suggest that human gastric carcinomas may express functional cytokine receptors, including the IL-2Rgc commonly found in association with the lymphocyte IL-2R. These receptors may represent novel targets for directing cytokine-based therapy.

Biopsy↗
PubMedDate not supplied

Cytochrome oxidase in the human visual cortex: distribution in the developing and the adult brain.

Cytochrome-oxidase (CO) histochemistry has revealed important functional subdivisions, modules, and processing streams in the macaque visual cortex. The present study is aimed at analyzing the development and characteristics of CO patterns in the human visual cortex by means of histochemistry and immunohistochemistry. At 26 weeks of gestation, both the ventricular and subventricular zones had low levels of CO, while the cortical plate had moderate levels of CO. At birth, supragranular CO-rich zones (puffs) were not clearly organized, indicating that the development of puffs in the neonatal striate cortex lags behind that of the macaque monkey, whose puffs appear weeks before birth. Puffs were more clearly discernible in human cortex at postnatal day 24, and became well organized by the fourth postnatal month. Layer IVc alpha in the neonate exhibited a higher level of activity and amount of CO than the central portion of IVc beta, which contained a dense aggregate of small neurons. The base of IVc beta, however, was often as CO reactive as IVc alpha. In contrast, the majority of specimens available to us from the fourth postnatal month and from adults with no known neurological diseases had significantly greater CO reactivity in layer IVc beta than in IVc alpha. Layer VI was moderately reactive for CO throughout development. In V2, stripes with globular zones of high CO activity were sporadically present at birth, suggesting that their development may parallel or precede that of puffs in V1. These stripes with CO-rich globular zones became more prominent in the adult and radiated orthogonally from the V1/V2 border. They were not, however, clearly organized into alternating thick and thin stripes as they are in the squirrel monkey. Visual cortical areas beyond V2 exhibited high CO activity mainly in layers III and IV and moderate levels in VI, suggesting that sites associated with cortico-cortical pathways may be metabolically most active.

Adult↗
PubMedDate not supplied

Matrix-enabled gene transfer for cutaneous wound repair.

Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect, we have evaluated matrix-enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet-derived growth factor-A or -B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix-enabled gene transfer with molecular targeting, in which the DNA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds.

Animals↗
PubMedDate not supplied

Quantification of cerebral infarct size by creatine kinase BB isoenzyme.

Creatine Kinase BB isoenzyme (CKBB) has been shown to rise in the serum and CSF following acute cerebral injury. To test the hypothesis that brain infarct size could be estimated from the appearance and disappearance of CKBB in the serum and CSF, strokes of varying size were produced in twelve mongrel dogs by silastic emboli. The rate of disappearance, Kd of CKBB (-.00732 +/- 0.001 min-1 mean +/- SE, N = 8) was determined by injecting purified CKBB (25 IU) intravenously then measuring its disappearance. Following the embolic stroke, serum samples were taken hourly for 24 hours and then at intervals for up to 160 hours for measurement of CKBB by radioimmunoassay until the animals were sacrificed. The brains were then removed, fixed in formalin, cut in 2 mm sections and photographed. The area of the infarct was measured using high pad digitizer interfaced with an Apple computer. The infarct size was then calculated from the area and thickness. Using a one-compartment mathematical model, the infarct size was estimated from the amount of CKBB appearing in the serum, the Kd of CKBB, and the amount of CKBB depleted from tissue. The computed infarct size correlated well (r = 0.94) with the measured infarct size. This model may have value in testing therapeutic modalities in the intact animal.

Animals↗
PubMedDate not supplied

Synthesis of hydroxy and methoxy perylene quinones, their spectroscopic and computational characterization, and their antiviral activity.

Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light-induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the "bay region." The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (approximately 450-800 nm) and relatively more intense and narrow features at wavelengths < or = 350 nm. High-level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from S0 to S2 and to higher-lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest-energy trans methoxy ground state isomer and the lowest-energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light-induced antiviral activity to each other, but significantly less than that of hypericin.

Antiviral Agents↗
PubMedDate not supplied

Automated analysis of electromyographic (EMG) recordings during botulinum injections.

PURPOSE: Botulinum toxin is injected into extraocular muscles using electromyographic (EMG) guidance to confirm needle location prior to injection. The purpose of this study was to develop and test an automated, objective method of storing and grading EMG signal quality obtained during botulinum injection. A reliable, nonsubjective estimate of signal quality will enhance future studies of the complications or effectiveness of botulinum toxin injections into extraocular muscle. METHODS: Injections were administered using a standard procedure. The EMG was digitized, recorded, and analyzed using discrete Fourier transform and power spectrum analysis. Audible signal quality was also graded subjectively by the surgeon. Patients were followed to determine the clinical response to the injection. RESULTS: Eighteen patients (24 injections) were studied. Each sample was collected and analyzed in less than one second. The EMG contained signals over a range of frequencies from 50 to 500 Hz, with an average peak near 90 Hz. Substantial variability of the signal was observed between patients. Contracting muscle had a higher total power and peak frequency in most, but not all, cases. Total signal power correlated moderately with subjective estimates of signal quality. Neither subjective nor computer-derived signal quality estimates correlated with the response to injection or complications. CONCLUSIONS: Computerized signal analysis can automatically characterize EMG signal power and frequency distribution. Although this technique has the potential to identify needle location at the time of botulinum injection accurately, signal variability limited the clinical and research utility of the present protocol.

Botulinum Toxins↗
PubMedDate not supplied

Immunologically-mediated tumour cell apoptosis: the role of TRAIL in T cell and cytokine-mediated responses to melanoma.

Immune responses against human melanoma are common and are believed to influence the natural history of the disease. In particular, CD4 T cell infiltrates are associated with regression of primary melanoma and with responses to treatment with interferon-alpha2 (IFN-alpha2). Our studies have shown that CD4 T cells appear to kill melanoma by means of a member of the tumour necrosis factor (TNF) family expressed on their surface and called TNF related apoptosis inducing ligand (TRAIL). Moreover, sensitivity to TRAIL also predicts responsiveness of melanoma to CD4 T cells. TRAIL is not expressed on resting lymphocytes but is expressed at high levels after exposure to IFN-alpha2 and on activated T cells. Lymphocytes from melanoma patients in early stages of the disease show high levels of expression after exposure to IFN-alpha2 and IFN-gamma but expression was less on lymphocytes from stage IV patients. This may be due to factors from melanoma cells in that supernatants from some melanoma cultures suppressed IFN-alpha2 upregulation of TRAIL. Sensitivity of melanoma cells to TRAIL can be increased by inhibition of the activation of NF-kappaB and anti-apoptotic events downstream of NF-kappaB. These results suggest that TRAIL may be an important mediator of responses against melanoma induced by immunotherapy or by treatment with IFN-alpha2 and interleukin-2. Studies on surgical biopsies of melanoma however show that fresh isolates appear less sensitive to TRAIL-induced apoptosis and effective therapy may involve combinations with other agents.

Apoptosis↗
PubMedDate not supplied

[A rare cause of heart failure: hypocalcemic cardiopathy].

In this paper, the authors present the case of hypocalcemic cardiopathy observed in a female patient who underwent thyroidectomy which was complicated post-operatively by the development of hypoparathyroidism. Two attacks of heart failure experienced by this patient were improved by the administration of calcium in combination with digitalis treatment. A study of cases published in the medical literature reveals that this condition is a rare cause of heart failure which develops only in the course of chronic hypocalcemia, with few neuromuscular clinical manifestations. The dual negative inotropic and hypovolemic effects caused by hypocalcemia explain the efficacy observed with the administration of calcium therapy, while the usual symptomatic treatment of this condition is inadequate.

Calcium↗
PubMedDate not supplied

Erosive candida arthritis in a patient with disseminated candidiasis.

Candida arthritis of the knee joint of 9 months' duration is described in a leukemic patient. Examination of the joint at autopsy revealed no signs of osteomyelitis, despite the chronicity of the arthritic process, and only minimal fungal invasion of the cartilage in a eroded area.

Adult↗
PubMedDate not supplied

[Evaluation of malaria vector control measures in central Vietnam (1976-1991)].

Activities used to control malaria transmission in the pilot station of Vanh Canh in the Binh Dinh Province of central Vietnam from 1976 to 1991 have been evaluated. These activities were: spraying DDT in and around the houses in the villages and the settlements in the fields; spraying lambdacyalothrin in the houses; and use of bed-nets impregnated with permethrin. Their efficacy was measured by the number of fever episodes due to malaria infections among the population. The spraying of DDT in the houses was followed by a reduction of malaria infection by more than 90%. However, spraying of the settlements was not advantageous. The termination of DDT spraying was not followed by an increase of malaria infections. Spraying with lambdacyalothrin was slightly more effective than with pyrimiphos and DDT. The use of pesticide-impregnated bed-nets was efficient, especially in the villages far away from the forest. Thus, these activities can contribute to the control of the malaria endemic in central Vietnam.

Adolescent↗
PubMedDate not supplied

The laparoscopic approach for repair of Morgagni hernias.

BACKGROUND AND OBJECTIVES: Morgagni hernias are unusual congenital diaphragmatic hernias that are generally asymptomatic and discovered incidentally. Surgical treatment is indicated once the diagnosis is made. These hernias have traditionally been repaired by the open abdominal or thoracic approaches. We report a case of Morgagni hernia repaired successfully via the laparoscopic approach. METHODS AND RESULTS: The patient was noted to have a large anteromedial diaphragmatic hernia by chest radiograph and CT imaging. He underwent laparoscopy, during which the hernia was reduced and the defect repaired with mesh placement. We used intracorporeal suture placement to anchor the mesh. The patient recovered uneventfully after a short hospitalization. CONCLUSIONS: The laparoscopic approach for repair of Morgagni hernias offers diagnostic advantages as well as the potential for reduced morbidity when compared to laparotomy. We report intracorporeal knot-tying for fixation of the mesh to be a secure and satisfactory means to achieve the laparoscopic repair.

Adult↗