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Biomedical subjects

T Nguyen

Publications and source records attributed to T Nguyen.

At least 163 records · Page 9Linked to original sources

The gene for cherubism maps to chromosome 4p16.3.

Cherubism is a rare familial disease of childhood characterized by proliferative lesions within the mandible and maxilla that lead to prominence of the lower face and an appearance reminiscent of the cherubs portrayed in Renaissance art. Resolution of these bony abnormalities is often observed after puberty. Many cases are inherited in an autosomal dominant fashion, although several cases without a family history have been reported. Using two families with clinically, radiologically, and/or histologically proved cherubism, we have performed a genomewide linkage search and have localized the gene to chromosome 4p16.3, with a maximum multipoint LOD score of 5. 64. Both families showed evidence of linkage to this locus. Critical meiotic recombinants place the gene in a 3-cM interval between D4S127 and 4p-telomere. Within this region a strong candidate is the gene for fibroblast growth factor receptor 3 (FGFR3); mutations in this gene have been implicated in a diverse set of disorders of bone development.

Adult↗

Angiotensin II improves random-flap viability in a rat model.

Angiotensin II (AII) is a naturally occurring peptide that has been shown to be angiogenic, cause the proliferation of several primary cell types (including endothelial cells), accelerate the repair of dermal injuries, and increase production of growth factors and extracellular matrix. The effect of a single administration of AII on the viability and vascularity of a random flap was assessed in a rat model. In the control model, the viability of the distal portion of the flap was reduced consistently by postoperative day 8. Initially, AII was administered in an aqueous vehicle (phosphate-buffered saline [PBS]) and a viscous vehicle (10% carboxymethyl cellulose [CMC]). Administration of 1 mg per milliliter AII in PBS did not affect the viability of random flaps (1.2 x 7 cm) in this animal model. However, a single administration of a higher dose of AII in PBS (10 mg per milliliter) or 1 mg per milliliter AII in the CMC vehicle resulted in 67% of the grafts being fully viable at postsurgical day 12, in contrast to vehicle-treated control flaps, none of which were fully viable at day 12. Furthermore, the portion of the flap that was viable was increased significantly (p < or = 0.05). Subsequently, a study was conducted to assess the dose-response curve for AII in a CMC vehicle in this rat model. As the dose of AII was reduced, the percentage of animals with fully viable flaps and the percentage of the flap that was viable decreased correspondingly. Administration of 0.03 mg per milliliter AII and greater increased significantly (p < or = 0.05) the viability of the flaps. In conclusion, AII appears to be highly efficacious in increasing the percentage of distal flap surface area survival when administered as a single topical dose to the wound bed.

Analysis of Variance↗

Child abuse and dentistry: a study of knowledge and attitudes among dentists in Victoria, Australia.

Child abuse is a disturbingly common finding in society today. In view of the high proportion of orofacial injuries seen in victims of child abuse, dentists are in a strategic position to recognize and report suspected cases. The present study of 347 dentists in Victoria, Australia, assessed the level of knowledge and attitudes among dental professionals on the important issue of child abuse. While a high level of interest was shown by the participants towards this issue, a need for further information and training in the recognition and reporting of child abuse was seen in the survey findings. While dentists at present are not legally mandated in all states of Australia to report suspected cases of child abuse, the dental profession is in a key position to play an active role in the identification and reporting of this substantial community problem.

Adolescent↗

Differential expression of caprine beta-defensins in digestive and respiratory tissues.

We identified two novel beta-defensin precursors, preproGBD-1 and preproGBD-2, in the tissues of a goat. Although the precursors were identical in 96.8% of their bases and 88.2% (60 of 68) of their amino acids, preproGBD-1 was expressed principally in the tongue and respiratory tract, whereas preproGBD-2 expression predominated throughout the intestine. These findings exemplify the phenomenon of tissue-specific expression in a family of host defense peptides that arose before the avian and mammalian lineages diverged.

Amino Acid Sequence↗

Purification and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes.

We purified three proline-rich antimicrobial peptides from elastase-treated extracts of sheep and goat leukocytes and subjected two of them, OaBac5alpha and ChBac5, to detailed analysis. OaBac5alpha and ChBac5 were homologous to each other and to bovine Bac5. Both exhibited potent, broad-spectrum antimicrobial activity under low-concentration salt conditions. While the peptides remained active against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Listeria monocytogenes in 100 mM NaCl, they lost activity against Staphylococcus aureus and Candida albicans under these conditions. ChBac5 was shown to bind lipopolysaccharide, a property that could enhance its ability to kill gram-negative bacteria. Proline-rich Bac5 peptides are highly conserved in ruminants and may contribute significantly to their innate host defense mechanisms.

Amino Acid Sequence↗

Basal cell carcinoma in young adults: not more aggressive than in older patients.

BACKGROUND: An increased incidence of sporadic basal cell carcinoma (BCC) has been observed in young adults within the last years. It has been hypothesized that these BCC in younger subjects might be more aggressive compared to BCC in the elderly. OBJECTIVE: To compare BCC recurrence rates between young and older patients. METHODS: Retrospective study of patients under the age of 35 years (group 1) with previously untreated BCC and comparison with BCC in patients older than 35 years (group 2). Each patient in group 1 was matched with 2 patients in group 2. RESULTS: 70 patients in group 1 and 140 patients in group 2 were included. The median follow-up was 76 months. In group 1, 13% of the BCC were of the morphea-like type and 9% in group 2 (p = 0.30), respectively. The 5-year recurrence rate was 4.6% in group 1 and 9.8% in group 2. They did not significantly differ between the two groups (log rank test p = 0.48). CONCLUSION: BCC in young patients are not more aggressive than in older patients.

Adult↗

The utility of daily therapeutic thoracentesis for the treatment of early empyema.

STUDY OBJECTIVES: To determine if therapeutic thoracentesis is as effective as early chest tube placement or no drainage procedure in the treatment of early empyema in rabbits. DESIGN AND INTERVENTIONS: An empyema, as evidenced by gross pleural pus and a decreased pleural fluid pH and glucose level, was induced in 49 rabbits. The rabbits were divided into three groups: 16 underwent daily therapeutic thoracentesis starting at 48 h, 14 underwent chest tube placement at 48 h, and 19 served as controls. RESULTS: The mortality rate in the therapeutic thoracentesis group (0/16) did not differ significantly from that in the chest tube group (3/14) or that in the control group (6/19). At autopsy at 10 days, the gross empyema score in the therapeutic thoracentesis group (2.1 +/- 0.3) was significantly lower (p < 0.05) than that in the chest tube group (2. 8 +/- 0.3) or the control group (3.5 +/- 0.2). The mean pleural peel score of 5.8 +/- 1.1 in the therapeutic thoracentesis group was significantly less (p < 0.05) than the score for the nonintervention control group (13.4 +/- 1.6). CONCLUSIONS: From this study, we conclude that therapeutic thoracentesis is at least as effective as early chest tube placement for the treatment of early empyema using our rabbit model of empyema.

Animals↗

Cortical motor potential alterations in chronic fatigue syndrome.

Premovement, sensory, and cognitive brain potentials were recorded from patients with Chronic Fatigue Syndrome (CFS) in four tasks: i) target detection, ii) short-term memory, iii) self-paced movement, and iv) expectancy and reaction time (CNV). Accuracy and reaction times (RTs) were recorded for tasks i, ii, and iv. Results from CFS patients were compared to a group of healthy normals. Reaction times were slower for CFS patients in target detection and significantly slower in the short-term memory task compared to normals. In target detection, the amplitude of a premovement readiness potential beginning several hundred milliseconds prior to stimulus onset was reduced in CFS, whereas the poststimulus sensory (N100) and cognitive brain potentials (P300) did not differ in amplitude or latency. In the memory task, a negative potential related to memory load was smaller in CFS than normals. The potentials to self-paced movements and to expectancy and RT (CNV) were not different between groups. The findings in CFS of slowed RTs and reduced premovement-related potentials suggest that central motor mechanisms accompanying motor response preparation were impaired in CFS for some tasks. In contrast, measures of neural processes related to both sensory encoding (N100) and to stimulus classification (P300) were normal in CFS.

Adult↗

Induction of differentiation and apoptosis in the prostate cancer cell line LNCaP by sodium butyrate and galectin-1.

Galectin-1 has been implicated in the process of vertebrate developmental regulation. Sodium butyrate is an established differentiation-inducing agent and has been shown to increase galectin-1 expression in colon carcinoma cells. We studied the roles of butyrate and galectin-1 in the induction of differentiation and apoptosis in the prostate cancer cell line LNCaP. Treatment of LNCaP cells with butyrate resulted in induction of galectin-1 expression in a time- and dose-dependent manner. Treatment with butyrate also resulted in inhibition of proliferation, morphologic changes consistent with a differentiated phenotype, and induction of apoptosis. Prostate specific antigen expression was transiently reduced. To determine which of these effects might be secondary to the induction of galectin-1, LNCaP cells were transfected with a galectin-1 expression vector. The transfected cells displayed growth inhibition and an increased rate of apoptosis. PSA expression was not affected. We conclude that galectin-1 may be responsible for many of the phenotypic changes resulting from butyrate treatment and may function downstream in the pathway of butyrate-induced differentiation. We also found PSA to be somewhat inconsistent as an indicator of differentiation of LNCaP cells, likely due to other factors influencing its expression.

Apoptosis↗

Differential expression of endogenous galectin-1 and galectin-3 in human prostate cancer cell lines and effects of overexpressing galectin-1 on cell phenotype.

We have analyzed the expression of galectin-1 and galectin-3 in four human prostate carcinoma cell lines. Northern analysis and immunoblotting experiments showed that three cell lines express both galectins. However, only galectin-1 was detected on the surface of these cells. The LNCaP line expressed neither galectin. LNCaP was transfected with galectin-1 and four clones were isolated, all of which expressed galectin-1 on the cell surface. Kinetics of binding to extracellular matrix proteins appeared to be accelerated in the transfected lines, but overall binding was not enhanced. When the same experiments were performed in the presence of EDTA to eliminate the effects of integrins, binding of a galectin-1 clone to laminin and fibronectin was increased relative to the control cell line. We propose that galectins may contribute to the adhesive properties of some prostate cancer cells.

Antigens, Differentiation↗

Postinfarction survival and inducibility of ventricular arrhythmias in the spontaneously hypertensive rat : effects of ramipril and hydralazine.

BACKGROUND: Hypertensive patients with left ventricular hypertrophy (LVH) have been found to have greater peri-infarction and postinfarction mortality. In this study, we evaluated the postinfarction survival, susceptibility to ventricular arrhythmias, and degree of LVH and cardiac fibrosis in the spontaneously hypertensive rat (SHR) and the effects of the ACE inhibitor ramipril and the direct vasodilator hydralazine on these characteristics. METHODS AND RESULTS: An acute myocardial infarction (MI) was produced by ligation of the left anterior descending coronary artery. Rats were randomized to either control (n=50), hydralazine (n=41), or ramipril (n=45). Treatments were started 4 hours after infarction and continued for 8 weeks. Ramipril and hydralazine reduced arterial pressure similarly. Medications were stopped 72 hours before euthanasia, at which time hemodynamic, programmed electrophysiological stimulation (PES), and morphological studies were performed. Mortality was decreased in ramipril (56%) compared with hydralazine (78%) and control (82%) SHRs (P=0.008). This was accompanied by a decrease in myocardial hypertrophy and fibrosis and a decrease in inducibility of ventricular arrhythmias by PES in the ramipril group regardless of MI size. Treatment with hydralazine had little or no effect on LVH and cardiac fibrosis and did not modify inducibility of ventricular arrhythmias by PES. Ramipril but not hydralazine prevented the increase in LV end-diastolic pressure in rats with large MIs. CONCLUSIONS: In the SHR, the ACE inhibitor ramipril reduces LVH, cardiac fibrosis, and susceptibility to ventricular arrhythmias by PES and improves survival and LV function. Despite a similar decrease in arterial pressure, hydralazine does not have these beneficial effects.

Angiotensin-Converting Enzyme Inhibitors↗

Role of Ca2+/K+ ion exchange in intracellular storage and release of Ca2+.

Although fluctuations in cytosolic Ca2+ concentration have a crucial role in relaying intracellular messages in the cell, the dynamics of Ca2+ storage in and release from intracellular sequestering compartments remains poorly understood. The rapid release of stored Ca2+ requires large concentration gradients that had been thought to result from low-affinity buffering of Ca2+ by the polyanionic matrices within Ca2+-sequestering organelles. However, our results here show that resting luminal free Ca2+ concentration inside the endoplasmic reticulum and in the mucin granules remains at low levels (20-35 microM). But after stimulation, the free luminal [Ca2+] increases, undergoing large oscillations, leading to corresponding oscillations of Ca2+ release to the cytosol. These remarkable dynamics of luminal [Ca2+] result from a fast and highly cooperative Ca2+/K+ ion-exchange process rather than from Ca2+ transport into the lumen. This common paradigm for Ca2+ storage and release, found in two different Ca2+-sequestering organelles, requires the functional interaction of three molecular components: a polyanionic matrix that functions as a Ca2+/K+ ion exchanger, and two Ca2+-sensitive channels, one to import K+ into the Ca2+-sequestering compartments, the other to release Ca2+ to the cytosol.

Adenosine Triphosphate↗

Differential effects of peptide histidine isoleucine (PHI) and related peptides on stimulation and suppression of neuroblastoma cell proliferation. A novel VIP-independent action of PHI via MAP kinase.

The growth rate of rodent embryonic neuroblasts and human neuroblastoma cell lines is regulated in part by autocrine or paracrine actions of neuropeptides of the family that includes vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and pituitary adenylate cyclase-activating peptide (PACAP). These peptides act via seven transmembrane G-protein-linked receptors coupled to cAMP elevation, phospholipase C activation, intracellular Ca2+ release, and/or of mitogen-activated protein (MAP) kinase activation. Here we investigated the action of these peptides on the mouse neuroblastoma cell line Neuro2a. PHI and VIP inhibited proliferation at concentrations as low as 10(-13) M and 10(-10) M, respectively. In contrast, PACAP action was biphasic, with stimulation occurring at subnanomolar doses and inhibition at higher doses. Peptide actions were studied further by measuring cAMP and ERK1/2 MAP kinase activity and by assessing 3H-thymidine incorporation in conjunction with a panel of signal transduction pathways inhibitors. The data obtained indicated that the PHI-inhibitory and PACAP-stimulatory activities were mediated by corresponding changes in activity of the MAP kinase pathway and independent of protein kinase A (PKA) or protein kinase C (PKC). In contrast, the inhibitory actions of VIP and PACAP were specifically blocked by antagonists of PKA. Northern blot analysis revealed gene expression for only the PACAP-preferring (PAC1) receptor. However, binding experiments using 125I-labeled PACAP27, PHI, and VIP, demonstrated the presence of PACAP-preferring sites, bivalent VIP/PACAP sites, and PHI-binding sites that did not interact with VIP. The studies demonstrate potent regulatory actions of PACAP, PHI, and VIP on neuroblastoma cell proliferation which appear to be mediated by multiple subsets of receptors which differentially couple to MAP kinase and PKA signaling pathways.

Animals↗

Disruption of dopamine D1 receptor gene expression attenuates alcohol-seeking behavior.

The role of the dopamine D1 receptor subtype in alcohol-seeking behaviors was studied in mice genetically deficient in dopamine D1 receptors (D1 -/-). In two-tube free choice limited (1-5 h) and continuous (24 h) access paradigms, mice were exposed to water and increasing concentrations of ethanol (3%, 6% and 12% w/v). Voluntary ethanol consumption and preference over water were markedly reduced in D1 -/- mice as compared to heterozygous (D1 +/-) and wild-type (D1 +/+) controls, whereas overall fluid consumption was comparable. When offered a single drinking tube containing alcohol as their only source of fluid for 24 h, D1 -/- mice continued to drink significantly less alcohol than D1 +/+ and D1 +/- mice. Dopamine D2 receptor blockade with sulpiride caused a small but significant reduction in alcohol intake and preference in D1 +/+ mice and attenuated residual alcohol drinking in D1 -/- mice. Dopamine D1 receptor blockade with SCH-23390 very effectively reduced alcohol intake in D1 +/+ and D1 +/- mice to the level seen in untreated D1 -/- mice. These findings suggest involvement of both dopamine D1 and D2 receptor mechanisms in alcohol-seeking behavior in mice; however, these implicate D1 receptors as having a more important role in the motivation for alcohol consumption.

Alcohol Drinking↗

Strategies to decrease costs associated with GBS prophylaxis in preterm gestations.

Objective: 1) To evaluate the costs associated with a practice of routinely culturing women for Group B beta-Streptococcus (GBS) who are at risk for preterm delivery. 2) To evaluate the charges associated with a policy of empiric antibiotic therapy in women suspected of imminent delivery prior to 37 weeks gestation.Methods: In our hospital, women who present with preterm contractions (PTC), preterm labor (defined as uterine contractions resulting in cervical change, PTL), and preterm rupture of the membranes (PROM) were cultured for GBS. Women with PTL and PROM received parenteral antibiotic therapy pending availability of culture results (48 hours). We reviewed the records of women who participated in a study to determine the sensitivity and specificity of a rapid test for GBS (Am J Obstet Gynecol 1997;176:S35). Results of the Lim broth culture, our gold standard, were used for this analysis. The charges for performing cultures ($32/culture) and administering intravenous ampicillin ($54/dose) were calculated.Results: There were 118 women with PTC, 52 women with PTL, and 64 with PROM. Thirty-four (14.5%) of the cultures were positive. The results are presented below.In women with PTC, the incidence of GBS was 12.7%. The culture results were available and guided care in only the 6 women who delivered between 2 and 7 days. In women with PTL the incidence of positive cultures was 11.5%. All of the women received antibiotics pending results of cultures. The majority of the women had delivery delayed 48 hours until results were available. Care was modified in the 7 women who delivered between 2 and 7 days. In women with PROM the incidence of GBS was 20.3%. The culture results were available and guided therapy in 11 women.Conclusions: Our findings suggest that GBS cultures have limited clinical value in women with PTC. Only 6 women, 5.5%, had their care modified as a result of the cultures, at a cost of $3776. In women with PTL, we over-treated the majority of women with antibiotics, most of whom delivered after culture results were available. Cultures had minimal impact on management. Antibiotics should be reserved for women whose labor is progressing on tocolysis. In women with PROM, most delivered prior to availability of culture results. We would have saved $2048 had no cultures been obtained. These results are probably irrelevant, if routine antibiotic administration is utilized in PROM to prolong latency intervals regardless of GBS status.

Journal Article↗