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Biomedical subjects

T Tran

Publications and source records attributed to T Tran.

At least 73 records · Page 4Linked to original sources

Childhood hearing impairment: processing dependencies in multidimensional speech perception for an auditory level of analysis.

OBJECTIVE: Our purpose was to determine whether the influence of childhood hearing impairment (HI) on multidimensional speech processing is a purely linguistic effect or whether childhood HI also affects the processing of speech dimensions representing an auditory level of analysis. DESIGN: The processing dependencies characterizing the two dimensions of talker-gender and spatial location were studied in 40 children with HI and in two normal-hearing (NH) comparison groups representing similar chronological ages (N = 30) or similar vocabulary skills (N = 70). The processing interactions were assessed with a speeded selective-attention task requiring listeners to attend selectively to the gender of the talker and to ignore the spatial location and vice versa. The logic is that performance for the target dimension will not be affected by what is happening on the nontarget dimension if the dimensions are processed independently. On the other hand, if the dimensions are not processed independently, listeners will not be able to attend selectively and performance for the relevant dimension will be affected by what is happening on the irrelevant dimension. In the latter case, results may be analyzed in terms of Garner interference (the effect on performance of irrelevant variability in the to-be-ignored dimension) (Garner, 1974a) and Simon interference (the effect on performance of an irrelevant spatial source) (Simon, 1990). RESULTS: Overall results in all listeners, those with NH or HI, showed significant interference when the participants were attending to the gender of the talker and ignoring spatial location and vice versa. The talker-gender and spatial-location dimensions of speech were not processed independently by these children. When the processing interactions were compared between the NH and HI groups, the presence of childhood HI as a general rule significantly diminished the degree of interference from spatial location. The degree of interference from the gender of the talker, on the other hand, remained normal in the presence of childhood HI. All listeners seemed stimulus bound by the gender of the talker. The degree of Garner interference did not show age-related or degree of loss-related change. The degree of Simon interference showed significant change as a function of age in the children with mild-moderate HI, but not in the children with severe HI. The developmental function for Simon interference in the children with mild-moderate HI was delayed to a degree that corresponded to the duration of the auditory deprivation. CONCLUSIONS: The overall pattern of results indicates that the influence of childhood HI on multidimensional speech processing is not a purely linguistic effect.

Age Factors↗

Absence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in human subgingival plaque.

Little is known about the presence of common medical pathogens in the human oral cavity. Using a 16S rRNA-based PCR identification method, this study determined the occurrence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in subgingival plaque from 50 adults with advanced periodontitis. Each patient contributed samples from 3 deep periodontal pockets collected by paper points. The PCR primers were for P. asaccharolytica 5'-CTC TAG CTA GAG TGT ACT GG-3' and 5'-ATA GGG TTT ATA GAT TAG CTC TCT-3', for B. fragilis 5'-AAT GAT TCC GCA TGG TTT CAT TA-3' and 5'-GCG GTG ATT GCT CAC TGA CA-3', and for C. pneumoniae 5'- TGA CAA CTG TAG AAA TAC AGC-3' and 5'-CGC CTC TCT CCT ATA AAT-3'. The primers yielded a single amplicon with the respective reference strains and produced no amplicon with colonies of 25 groups of oral organisms. None of the three test species were detected in any of the 50 pooled subgingival samples tested. P. asaccharyolytica, B. fragilis and C. pneumoniae do not seem to be part of the periodontopathic microbiota in humans.

Adult↗

Assessment of fetal well-being in methadone-maintained pregnancies: abnormal nonstress tests.

OBJECTIVE: To investigate parameters of fetal well-being (characteristics of nonstress test, NST, and antepartum fetal heart rate, FHR, patterns) and selected neonatal outcomes in pregnant women on methadone maintenance. STUDY DESIGN: A matched case-control study of methadone-treated women receiving prenatal and intrapartum care at a Bronx municipal hospital during 1992-1994. 102 NSTs obtained from 24 methadone-treated women after 35 weeks of pregnancy were compared to 96 NSTs from a control group (n = 24), matched for maternal age, parity, and gestational age. All NSTs were evaluated for general characteristics including time interval between initiation and achievement of reactive NST (2 accelerations > or = 15 bpm lasting for at least 15 s in a 20-min period), baseline, amplitude of fluctuation, frequency of fluctuation, accelerations and decelerations. The scoring system described by Lyons et al. was used for all NSTs. All nonreactive NSTs were followed with biophysical profile tests. RESULTS: The frequency of nonreactive NSTs was significantly higher for methadone-maintained women compared to controls (19.6 vs. 4.2%; p < 0.01). The average length of time to achieve reactive NST was significantly (p = 0.0016) longer for the methadone-treated group when compared to controls (35.50 +/- 20.96 vs. 14.85 +/- 9.03 min). The total score (Lyons et al.) was significantly lower (p < 0.0007) for the methadone-treated group compared to controls. Mean birth weight, Apgar scores at 1 and 5 min, meconium, and umbilical cord artery pH were not significantly different for methadone-exposed neonates compared to controls. CONCLUSION: Methadone-maintained pregnancies are significantly associated with a higher incidence of nonreactive NSTs, longer intervals to achieve reactive NSTs and lower NST scores compared to controls. This may reflect an altered response in fetal central nervous system neurotransmitters and changes in fetal behavior induced by methadone.

Abnormalities, Drug-Induced↗

Hormone replacement therapy and the risk of breast lesions that predispose to cancer.

To determine whether postmenopausal individuals being treated with hormone replacement therapy (HRT) have an increased risk for lesions that predispose to breast cancer, 156 women with benign breast lesions were retrospectively studied. Their ages ranged from 43 to 88. Each patient underwent a breast biopsy from 1991 to 1995. It was determined from chart review whether each of these patients had been treated with HRT. Fifty-seven of these patients had a biopsy finding that predisposed the patient to future breast cancer. The predisposing lesions included sclerosing adenosis, intraductal papilloma, and epithelial hyperplasia with atypia. Of these 57 patients, 36 (63%) were being treated with HRT. Only 30 of the 99 patients (30%) with nonproliferative lesions were treated with HRT (odds ratio, 3.9; P < 0.0005). On the basis of the results of this study, we believe that the use of HRT may promote lesions that predispose to cancer. This suggests that patients treated with HRT require vigilant surveillance by way of examination and mammography.

Adult↗

Successful treatment of canine malignant histiocytosis with the human major histocompatibility complex nonrestricted cytotoxic T-cell line TALL-104.

The human MHC nonrestricted cytotoxic T-cell line TALL-104 exerts potent antitumor effects in animal models with both induced and spontaneous cancers. The present report documents the ability of systemically delivered TALL-104 cells to induce durable clinical remissions in four of four dogs with malignant histiocytosis (MH). The animals received multiple i.v. injections of lethally irradiated (40 Gy) TALL-104 cells at a dose of 10(8) cells/kg, with (two dogs) or without (two dogs) cyclosporin A, followed by monthly boosts. No significant clinical or laboratory toxicities developed during cell therapy; interestingly, a strong correlation was found between the dogs' clinical and immunological responses. One dog with advanced disease (intrathoracic involvement) refractory to chemotherapy achieved a complete remission (CR) within 2 months of the first TALL-104 cell infusion. This dog died 14 months later of unrelated causes: histological analysis of its organs postmortem revealed no evidence of neoplasia, thus confirming the achievement of CR also at the pathological level. The other three dogs with MH that at diagnosis had multiple s.c. and cutaneous lesions and lymphadenopathy, but no visceral involvement, were treated with TALL-104 cells as single agent (no chemotherapy was administered). Two of these dogs achieved a CR soon after cell therapy, and the third dog had two long-lasting partial responses; CR in this dog was later achieved by combined administration of chemotherapy and cell therapy. None of the three dogs that received cell therapy at diagnosis developed visceral disease in the approximately 9-22 months of follow-up. The clinical responses experienced by all four MH cases to TALL-104 cell therapy suggest the high responsiveness of this canine tumor to these xenogeneic effectors and their therapeutic potential even in the most aggressive forms of the disease.

Animals↗

Delayed maturation of CD4- CD8- Fc gamma RII/III+ T and natural killer cell precursors in Fc epsilon RI gamma transgenic mice.

Fc epsilon RI gamma (gamma) is a member of a group of related proteins (the zeta-family dimers) that function as signal-transducing components of both Fc receptors and the T cell antigen receptor (TCR). Analysis of gamma expression during fetal thymus ontogeny revealed that it is expressed in early thymocytes, before the initiation of clonotypic TCR-alpha and TCR-beta gene rearrangement but is down-regulated in most adult thymocytes. To explore a possible role for gamma in thymocyte development, we generated transgenic mice in which this protein was overexpressed at all stages of ontogeny. Overexpression of gamma inhibited the maturation of T cells as well as natural killer (NK) cells. The developmental effects were transgene dose related and correlated with markedly delayed maturation of fetal CD4-CD8- FcRII/III+ thymocytes, cells thought to include the progenitors of both T and NK cells. These results suggest that the zeta and gamma chains serve distinctive functions in thymocyte development and indicate that Fc receptor(s) may play an important role in regulating the differentiation of early progenitor cells within the thymus.

Animals↗

Evaluation of the importance of maternal history of diabetes and of mitochondrial variation in the development of NIDDM.

In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both parents living, parental diabetic status was established through previously diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no significant difference between diabetes prevalence in mothers and fathers (60 vs 53 (76% vs 67%), respectively, p = 0.22). 'Age at diabetes diagnosis' survival curves did differ according to parental gender (p = 0.02) but this may reflect gender differences in health provision rather than pathophysiology. No maternal excess effects of the magnitude evident in previous studies were detected, suggesting either ethnic differences or overestimation of the maternal effect when reported histories of parental diabetes have been used. The tRNA(Leu(UUR) gene region was studied for diabetes-associated variation given the role of mutations in this gene in some pedigrees displaying maternal transmission of NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS mutation at nt3243. However, sequencing identified two variants of potential importance: (a) at nt3290 in the tRNA(Leu(UUR) gene, seen in 7/142 diabetic and 1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85 subjects, respectively (p = 0.51)). Further studies are needed to determine the relevance of these variants to the development of NIDDM.

Adult↗

Evaluation of urethral strictures and associated abnormalities using high-resolution and color Doppler ultrasound.

OBJECTIVES: To study the role of urethral sonography and color Doppler imaging in the evaluation of patients with urethral strictures and associated abnormalities. METHODS: We reviewed our experience with 41 urethral sonographic studies in 35 patients and compared them to 33 retrograde urethrograms. For 6 recent cases, we also used color Doppler imaging to assess spongiosal tissue blood flow and the location of urethral arteries. RESULTS: Both retrograde urethrography and urethral sonography assessed the caliber and length of the strictures well. Urethral sonography provided additional information about stricture involvement of the spongiosum, location of urethral arteries, and associated abnormalities (that is, periurethral abscess and urethrocutaneous fistula). This information was useful for the clinical stratification of urethral stricture disease and the planning of treatment. CONCLUSIONS: With the advantages of avoiding radiation to testis, providing real-time evaluation of the distensibility of the urethra, and having the capacity of assessing spongiosum and periurethral tissue involvement and urethral artery location, urethral sonography appears to offer more than retrograde urethrography for the evaluation of anterior urethral stricture.

Adolescent↗

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

BRCA2 Protein↗

Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer.

The lifetime risk of breast cancer may approach 80-90% in women who have germline mutations of either of two genes, BRCA1 or BRCA2. A single BRCA1 mutation, 185delAG, has been noted in approximately 20% of Ashkenazi Jewish women with early onset breast cancer and in 0.9% of the Ashkenazi population. We recently detected a 6174delT frameshift mutation in BRCA2 in an hereditary breast cancer kindred of Ashkenazi Jewish ancestry. Here, we investigated the frequency of this mutation in 200 women with early-onset breast cancer. Six of 80 Ashkenazi Jewish women (8%) diagnosed with breast cancer before the age of 42, wer heterozygous for the 6174delT mutation, compared to none of 93 non-Jewish women diagnosed with breast cancer at the same age (P = .005). These cases were ascertained without regard to family history. Two of 27 (7%) additional Jewish families in which the proband was diagnosed with breast cancer at age 42 to 50 and had a family history of breast or ovarian cancer had germline 6174delT mutations. The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation BRCA2 together may account for over a quarter of all early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.

Adult↗

Dosimetry of an incident involving 14C.

High level contamination was observed on two workers during a routine hand check of personnel leaving a laboratory where barium carbonate labeled with 14C was handled. A third worker was found to have been exposed to airborne 14C (carbonate) aerosol during the investigation. Urinary excretion analysis and in vivo monitoring were carried out. This paper presents the results of more than one year of lung counting using phoswich detectors and gives some indication about the metabolism of the 14C over that period. Doses were difficult to estimate due to lack of information in the literature. Estimates were based on default parameters and information gathered in this study using ICRP 30 and the new ICRP lung models. These ranged from 0.3 mSv to 3 mSv depending on the assumptions and models.

Barium↗

Cytotoxic effects of TGF-alpha-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells.

The epidermal growth factor (EGF) receptor is overexpressed in human pancreatic cancers and cultured cell lines. TP40 is a chimeric protein composed of transforming growth factor-alpha (TGF-alpha) linked to a modified Pseudomonas exotoxin A (PE40) that exerts growth inhibitory effects on cells bearing a high number of EGF receptors. Therefore, we compared the effect of TP40 on the growth of Chinese hamster ovary (CHO), cells expressing varying levels of the EGF receptor and on the growth of two human pancreatic cancer cell lines. The growth of CHO cells devoid of endogenous EGF receptors was minimally altered by high concentrations of TP40, even following a 72-h incubation period. In contrast, in CHO cells expressing approximately 95,000 and 438,000 EGF receptors per cell, one-half maximal growth inhibition occurred at 5 and 3 ng/ml TP40, respectively. Following a 72-h incubation in T3M4 and COLO 357 human pancreatic cancer cells, one-half maximal growth inhibition occurred at 0.2 and 0.4 ng/ml TP40, respectively. This effect was significantly greater than that of native Pseudomonas exotoxin A. These findings indicate that human pancreatic cancer cells are markedly sensitive to the growth inhibitory effects of TP40 and raise the possibility that TP40 may have a therapeutic role in this disorder.

Animals↗

Effect of omeprazole on sodium and potassium output in pentagastrin-stimulated equine gastric contents.

OBJECTIVE: To better characterize the source of the large nonparietal secretory response to pentagastrin (PG) expressed in gastric contents of cannulated horses. ANIMALS: Adult cross-bred horses: 4 geldings and 1 mare. PROCEDURE: Horses were prepared by surgical insertion of a silastic gastric cannula from which gastric contents after feed was withheld could be continuously collected by gravity drainage. During experiments, the horses were lightly restrained in stocks, the gastric cannula was opened, and a catheter was inserted into a jugular vein. Over the next 5 hours, gastric contents were collected in 15-minute aliquots for which volume, pH, [Na+], and [K+] were measured. During the first hour, treatment was not administered. At the start of the second hour, either 0.5 mg of omeprazole (OME; dissolved in glycerol formal)/kg of body weight, or 0.9% NaCl (PSS) of comparable volume, was given IV at random as a bolus. At the start of the third hour, IV infusion of PG (6 micrograms/ kg/h) was started and continued for the next 2 hours. RESULTS: The response to PG in the PSS-treated horses was similar to that previously seen-significant decrease in pH and increase in volume of gastric contents, and no change in [K+] and [Na+], but a modest volume-related increase in their respective outputs. After OME treatment, pH of the contents increased sharply and remained between 5 and 6 throughout PG infusion. Sodium concentration significantly increased after OME and virtually paralleled the pH response throughout the rest of the experiment; volume of gastric contents significantly increased in response to PG infusion and resulted in a significant increase in Na output. There was no change in K output in OME-treated animals. CONCLUSIONS: PG induces a marked, nonparietal, secretory response into the gastric contents of cannulated horses. The volume and [Na+] of this response was maintained after pretreatment with OME, although the pH of the contents became basic, indicating that this nonparietal response is not mediated by an OME-sensitive proton pump.

Animals↗

Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor necrosis factor alpha, and nitric oxide in glial cultures derived from fetal, neonatal, and adult human brain.

Although microglia are the only cells found to be productively infected in the central nervous system of acquired immunodeficiency disease syndrome (AIDS) patients, there is extensive white and gray matter disease nonetheless. This neuropathogenesis is believed to be due to indirect mechanisms other than infection with human immunodeficiency virus 1 (HIV-1). Cytokines and toxic small molecules have been implicated in the clinical and histopathological findings in CNS AIDS. Previously, we have demonstrated in rodent glial cultures the presence of biologically active epitopes of gp120 and gp41 that are capable of inducing interleukin 1 and tumor necrosis factor alpha. In this study, we map the HIV-1 envelope epitopes that induce nitric oxide, inducible nitric oxide synthase, interleukin 1, and tumor necrosis factor alpha in human glial cultures. Epitopes in the carboxy terminus of gp120 and the amino terminus of gp41 induce these proinflammatory entities. In addition, we compare HIV-1 infection and pathology in glial cells derived from human brain taken at different states of maturation (fetal, neonatal, and adult brain) in an effort to address some of the clinical and histological differences seen in vivo. This study demonstrates that, in the absence of virus infection and even in the absence of distinct viral tropism, human glia respond like rodent glia to non-CD4-binding epitopes of gp120/gp41 with cytokine and nitric oxide production. Differences among fetal, neonatal, and adult glial cells' infectivity and cytokine production indicate that, in addition to functional differences of glia at different stages of development, cofactors in vitro and in vivo may also be critical in facilitating the biological responses of these cells to HIV-1.

Adolescent↗

Leukocyte activation in the peripheral blood of patients with cirrhosis of the liver and SIRS. Correlation with serum interleukin-6 levels and organ dysfunction.

OBJECTIVE: Leukocyte adhesion plays an important role in inflammation. Adhesion molecules such as CD11b on polymorphonuclear neutrophil leukocytes (PMNs) up-regulate in response to tumor necrosis factor-alpha, interleukin-8 (IL-8), and other mediators that are involved in systemic inflammatory response syndrome (SIRS). This study examined the behavior of CD11b and other membrane molecules in SIRS in relation to serum cytokines and the severity of illness. DESIGN: Survey study. SETTING: Liver transplantation intensive care unit at a tertiary care center. PATIENTS: A consecutive sample of 22 patients admitted to the liver transplantation intensive care unit for complications related to cirrhosis of the liver in the absence of other disease. Sixteen of the patients developed SIRS and multiple organ dysfunction syndrome with suspected bacterial infections. Seven control subjects were also studied. MAIN OUTCOME MEASURES: Modified Goris organ failure score and Acute Physiology and Chronic Health Evaluation II score. RESULTS: Mean serum IL-6 levels, but not IL-1 beta or tumor necrosis factor-alpha levels, correlated with organ failure (r = 0.79, P < .001). Leukocyte cell-surface markers fluctuated from day to day. The mean of several values was more stable. Mean CD11b and CD35 on PMNs correlated with serum IL-6 level (r = 0.75, P < .001, and r = 0.77, P < .005, respectively). Up-regulation of both CD11b and CD35 display on PMNs correlated with organ failure (r = 0.74, P < .001, and r = 0.71, P < .01, respectively). Polymorphonuclear neutrophil leukocyte L-selectin, CD31, and CD16 were simultaneously decreased, consistent with PMN activation. Monocytes appeared to be activated, but the pattern of surface molecule display was different. CONCLUSIONS: In human SIRS, the circulating monocyte and PMN pools undergo alterations suggestive of leukocyte activation, including up-regulation of PMN CD11b in correlation with the serum IL-6 level and severity of organ dysfunction.

Adult↗