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Biomedical subjects

T E Young

Publications and source records attributed to T E Young.

At least 19 recordsLinked to original sources
PubMed2001

Developmental and thermal regulation of the maize heat shock protein, HSP101.

The plant heat stress protein, Hsp101, and the yeast ortholog, Hsp104, are required to confer thermotolerance in plants and yeast (Saccharomyces cerevisiae), respectively. In addition to its function during stress, Hsp101 is developmentally regulated in plants although its function during development is not known. To determine how the expression of Hsp101 is regulated in cereals, we investigated the Hsp101 expression profile in developing maize (Zea mays). Hsp101 protein was most abundant in the developing tassel, ear, silks, endosperm, and embryo. It was less abundant in the vegetative and floral meristematic regions and was present at only a low level in the anthers and tassel at anthesis, mature pollen, roots, and leaves. As expected, heat treatment resulted in an increase in the level of Hsp101 protein in several organs. In expanding foliar leaves, husk leaves, the tassel at the premeiosis stage of development, or pre-anthesis anthers, however, the heat-mediated increase in protein was not accompanied by an equivalent increase in mRNA. In contrast, the level of Hsp101 transcript increased in the tassel at anthesis following a heat stress without an increase in Hsp101 protein. In other organs such as the vegetative and floral meristematic regions, fully expanded foliar leaves, the young ear, and roots, the heat-induced increase in Hsp101 protein was accompanied by a corresponding increase in Hsp101 transcript level. However, anthers at anthesis, mature pollen, developing endosperm, and embryos largely failed to mount a heat stress response at the level of Hsp101 protein or mRNA, indicating that Hsp101 expression is not heat inducible in these organs. In situ RNA localization analysis revealed that Hsp101 mRNA accumulated in the subaleurone and aleurone of developing kernels and was highest in the root cap meristem and quiescent center of heat-stressed roots. These data suggest an organ-specific control of Hsp101 expression during development and following a heat stress through mechanisms that may include posttranscriptional regulation.

Amino Acid Sequence↗
PubMed2000

Regulation of programmed cell death in maize endosperm by abscisic acid.

Cereal endosperm undergoes programmed cell death (PCD) during its development, a process that is controlled, in part, by ethylene. Whether other hormones influence endosperm PCD has not been investigated. Abscisic acid (ABA) plays an essential role during late seed development that enables an embryo to survive desiccation. To examine whether ABA is also involved in regulating the onset of PCD during endosperm development, we have used genetic and biochemical means to disrupt ABA biosynthesis or perception during maize kernel development. The onset and progression of cell death, as determined by viability staining and the appearance of internucleosomal DNA fragmentation, was accelerated in developing endosperm of ABA-insensitive vp1 and ABA-deficient vp9 mutants. Ethylene was synthesized in vp1 and vp9 mutant kernels at levels that were 2-4-fold higher than in wild-type kernels. Moreover, the increase and timing of ethylene production correlated with the premature onset and accelerated progression of internucleosomal fragmentation in these mutants. Treatment of developing wild-type endosperm with fluridone, an inhibitor of ABA biosynthesis, recapitulated the increase in ethylene production and accelerated execution of the PCD program that was observed in the ABA mutant kernels. These data suggest that a balance between ABA and ethylene establishes the appropriate onset and progression of programmed cell death during maize endosperm development.

Abscisic Acid↗
PubMed2000

Programmed cell death during endosperm development.

The endosperm of cereals functions as a storage tissue in which the majority of starch and seed storage proteins are synthesized. During its development, cereal endosperm initiates a cell death program that eventually affects the entire tissue with the exception of the outermost cells, which differentiate into the aleurone layer and remain living in the mature seed. To date, the cell death program has been described for maize and wheat endosperm, which exhibits common and unique elements for each species. The progression of endosperm programmed cell death (PCD) in both species is accompanied by an increase in nuclease activity and the internucleosomal degradation of nuclear DNA, hallmarks of apoptosis in animals. Moreover, ethylene and abscisic acid are key to mediating PCD in cereal endosperm. The progression of the cell death program in developing maize endosperm follows a highly organized pattern whereas in wheat endosperm, PCD initiates stochastically. Although the essential characteristics of cereal endosperm PCD are now known, the molecular mechanisms responsible for its execution remain to be identified.

Apoptosis↗
PubMed1999

Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.

BACKGROUND: Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo. OBJECTIVES: To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis. METHODS: Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia. RESULTS: No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group. CONCLUSIONS: This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.

Analgesia↗
PubMed1999

Analysis of programmed cell death in wheat endosperm reveals differences in endosperm development between cereals.

Although maize endosperm undergoes programmed cell death during its development, it is not known whether this developmental feature is common to cereals or whether it arose inadvertently from the selection process that resulted in the enlarged endosperm of modern maize. Examination of wheat endosperm during its development revealed that this tissue undergoes a programmed cell death that shares features with the maize program but differs in some aspects of its execution. Cell death initiated and progressed stochastically in wheat endosperm in contrast to maize where cell death initiates within the upper central endosperm and expands outward. After a peak of ethylene production during early development, wheat endosperm DNA underwent internucleosomal fragmentation that was detectable from mid to late development. The developmental onset and progression of DNA degradation was regulated by the level of ethylene production and perception. These observations suggest that programmed cell death of the endosperm and regulation of this program by ethylene is not unique to maize but that differences in the execution of the program appear to exist among cereals.

Apoptosis↗
PubMed1999

Population-based study of chronic lung disease in very low birth weight infants in North Carolina in 1994 with comparisons with 1984. The North Carolina Neonatologists Association.

OBJECTIVE: To assess the pulmonary outcomes of very low birth weight (VLBW) infants in North Carolina in 1994 and to compare rates of survival and chronic lung disease (CLD) between 1994 and 1984 (see reference 2). METHODS: Data were collected prospectively by collaborators from all 13 neonatal intensive care units in North Carolina to determine survival and pulmonary outcomes of infants with birth weights of 500 to 1500 g. State vital statistics data were used to confirm completeness of the sample. CLD was defined as oxygen or ventilator therapy at 36 weeks' postmenstrual age (PMA). For comparisons with the 1984 cohort, survival and pulmonary outcomes of infants defined to be at risk for CLD (ventilated >48 hours and survived 30 days) were recorded at 30 days, 3 months, and 6 months of postnatal age. RESULTS: Outcome data were available for 1413 (92%) of the in-state VLBW live births. Of VLBW infants, 224 (15%) died before 48 hours of age. The overall rate of CLD in 1994 at 36 weeks' PMA was 25%. Rates by birth weight group were 57% for 500 to 750 g birth weight (BW), 41% for 751 to 1000 g BW, 19% for 1001 to 1250 g BW, and 8% for 1251 to 1500 g BW. Infants who received ventilator therapy for >48 hours accounted for 89% of the CLD cases. The CLD rate at 36 weeks' PMA in infants weighing 751 to 1500 g was 37% for those ventilated >48 hours versus 5% for those ventilated <48 hours (OR: 7.1; 95% CI: 4.4-11.3). Overall survival in 1994 was significantly higher for infants than in 1984 (78% vs 74%), most notably in infants 500 to 750 g BW (37% vs 24%), and 751 to 1000 g BW (82% vs 65%). When compared with 1984, the CLD rates in those infants defined to be at risk were significantly higher in 1994 at 30 days (68% vs 54%) and at 3 months (24% vs 15%) of postnatal age. For at-risk infants in 1994, there were fewer infants on the ventilator, but more infants on oxygen alone at all measured time points compared with 1984. CONCLUSION: Survival of VLBW infants has improved since 1984. Ventilator therapy for >48 hours remains a significant risk factor for CLD. The incidence of CLD has increased from 1984 to 1994 but has shifted from ventilator to oxygen therapy. bronchopulmonary dysplasia, epidemiology, infant, low birth weight, intensive care units, neonatal statistics, infant mortality, prospective studies.

Chronic Disease↗
PubMed1999

Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association.

OBJECTIVE: To identify risk factors for chronic lung disease (CLD) in a population-based cohort of very low birth weight infants, born in an era of surfactant usage. We specifically investigated the effects of antenatal steroids, nosocomial infection, patent ductus arteriosus (PDA), fluid management, and ventilator support strategies. METHODS: Data were prospectively collected on 1244 infants born in North Carolina in 1994 with birth weights 500 to 1500 g, and treated at 1 of the 13 intensive care nurseries across the state. The outcome of interest was CLD, defined as dependency on supplemental oxygen at 36 weeks' postmenstrual age. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression models. RESULTS: Among 865 survivors to 36 weeks' postmenstrual age, 224 (26%) had CLD. Nosocomial infection (OR: 2.0; 95% CI: 1.4-3.3), fluid intake on day 2 (OR: 1.06 per 10 mL increase; 95% CI: 1.01-1.11), and the need for ventilation at 48 hours of life (OR: 2.2; 95% CI: 1.3-3.7) were associated with an increased risk of CLD. Among infants ventilated at 48 hours, nosocomial infection (OR: 1.64; 95% CI: 1.02-2.62) and PDA (OR: 1.9; 95% CI: 1.2-3.1) were associated with an increased risk. No association was found with antenatal steroid receipt or increased levels of ventilator support. CONCLUSION: This analysis suggests that with widespread use of surfactant, nosocomial infection, PDA, and water balance persist as risk factors for CLD.

Chronic Disease↗
PubMed1997

Postnatal steroid therapy in neonates.

Dexamethasone treatment of neonates to facilitate weaning from mechanical ventilation has become increasingly common. Despite thousands of infants being treated, most studies fail to demonstrate an improvement in long-term pulmonary and neurodevelopmental outcome. Much controversy remains regarding who should be treated, when treatment should begin, what the proper dose is, how long treatment should continue, and how adverse effects can be minimized. Early treatment prior to the onset of significant pulmonary inflammation may be an approach that improves outcomes and allows for shorter treatment courses. Risk assessment tools using ventilator requirements, adrenal function, or markers of pulmonary inflammation may allow for improved patient selection. Future studies will need to include a large number of subjects and will need to be continued beyond the neonatal period to assess long-term pulmonary and neurodevelopmental outcome.

Dexamethasone↗
PubMed1994

The regulation of gene expression in transformed maize aleurone and endosperm protoplasts. Analysis of promoter activity, intron enhancement, and mRNA untranslated regions on expression.

Gene expression in the aleurone and endosperm is highly regulated during both seed development and germination. Studies of alpha-amylase expression in the aleurone of barley (Hordeum vulgare) have generated the current paradigm for hormonal control of gene expression in germinating cereal grain. Gene expression studies in both the aleurone and endosperm tissues of maize (Zea mays) seed have been hampered because of a lack of an efficient transformation system. We report here the rapid isolation of protoplasts from maize aleurone and endosperm tissue, their transformation using polyethylene glycol or electroporation, and the regulation of gene expression in these cells. Adh1 promoter activity was reduced relative to the 35S promoter in aleurone and endosperm protoplasts compared to Black Mexican Sweet suspension cells in which it was nearly as strong as the 35S promoter. Intron-mediated stimulation of expression was substantially higher in transformed aleurone or endosperm protoplasts than in cell-suspension culture protoplasts, and the data suggest that the effect of an intron may be affected by cell type. To examine cytoplasmic regulation, the 5' and 3' untranslated regions from a barley alpha-amylase were fused to the firefly luciferase-coding region, and their effect on translation and mRNA stability was examined following the delivery of in vitro synthesized mRNA to aleurone and endosperm protoplasts. The alpha-amylase untranslated regions regulated translational efficiency in a tissue-specific manner, increasing translation in aleurone or endosperm protoplasts but not in maize or carrot cell-suspension protoplasts, in animal cells, or in in vitro translation lysates.

Animals↗
PubMed1990

Metastatic carcinoma in the cervical lymph nodes from an occult primary: a conservative approach to the role of radiotherapy.

This retrospective study examines the results of treatment for cervical lymph node metastases from an unknown primary epithelial cancer of squamous cell or anaplastic histology. The analysis covers a series of 87 consecutive unselected patients at the Middlesex Hospital, London, in the years between 1954 and 1986. Fifty-eight patients received radiation therapy with a view to cure, 25 patients were treated with radiotherapy to a palliative dose, 1 patient only had a radical neck dissection, and 3 patients received no treatment apart from excision biopsy. In contrast to common practice in the United States, only a single patient received prophylactic radiation to the nasopharynx as part of the initial therapy. Overall actuarial survival for all patients (87) at 2 years was 43% and at 5 years 33%, and in the radically treated group (58) it was 52% and 40%, respectively. Only 6 of the 87 patients (7%) subsequently revealed a primary tumor above the clavicles. Overall disease control above the clavicles was achieved in 53% (46/87), but was 64% (37/58) in the radically treated group. Guidelines for radiation therapy are discussed in view of these results.

Adolescent↗
PubMed1989

Metastatic adenocarcinoma in the cervical lymph nodes from an occult primary.

Cervical lymph node metastases as the only site of disease is a rare presentation of an adenocarcinoma of unknown primary origin. This retrospective analysis examines the records of ten consecutive patients at the Middlesex Hospital with this diagnosis between 1954 and 1986. The diagnostic protocol employed and the results of radical treatment are evaluated. Nine patients received radiation therapy with intent to cure, and one patient had a radical neck dissection. Overall actuarial survival for all patients (10) at 2 years was 23% and at 5 years 0%. Only two of the 10 patients subsequently revealed a primary tumour--both below the clavicles. Disease control above the clavicles was not achieved in a single patient despite radical treatment.

Adenocarcinoma↗
PubMed1986

Combination chemotherapy of squamous cell carcinoma of the bronchus with cisplatinum and bleomycin followed by radiotherapy: results of a pilot study.

Thirteen patients were entered into an uncontrolled pilot study to investigate the response to, and toxicity of, a combination of cisplatinum (20 mg/m2) and bleomycin (6 mg/m2) infused daily for 5 days and repeated every 21 days up to a maximum of 4 cycles, in the treatment of squamous cell carcinoma of the bronchus. This regimen was subsequently followed by a split course of local irradiation. All patients have been followed to death. Six patients showed a partial response to chemotherapy while 7 showed no response or progressive disease. The median survival was 5 months. The median survival of the responders was 15 months and that of the nonresponders 3 months. Two patients developed the syndrome of inappropriate antidiuretic hormone secretion from which one died. The longest survivor, who died 26 months after the commencement of chemotherapy, had severe mediastinal and pulmonary fibrosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Comparative effects of nifedipine, verapamil, and diltiazem on experimental pulmonary hypertension.

The role of calcium-channel blocking agents in the treatment of pulmonary hypertension is not well defined. Consequently, the effects of diltiazem, nifedipine, and verapamil were compared in 3 groups of anesthetized dogs (n = 6 for each group). In each group, normoxic hemodynamic variables were recorded before and after increasing doses of diltiazem, nifedipine, and verapamil (5 X 10(-8) M/kg, low; 10(-7) M/kg, medium; and 10(-6) M/kg, high dose; given intravenously over 2 minutes). In addition, the effect of these doses on the pulmonary pressor responses to hypoxia (fractional inspired oxygen concentration [FIO2] 12%) and prostaglandin F2 alpha (PGF2 alpha) (5 micrograms/kg/min, intravenously for 4 minutes) was measured. During normoxia, high-dose nifedipine and verapamil decreased mean aortic pressure and systemic vascular resistance while increasing cardiac output in all dogs in both groups (p less than 0.01). Pulmonary vascular resistance, however, remained unchanged. High-dose diltiazem did not significantly alter cardiac output or pulmonary vascular resistance. During acute hypoxic pulmonary hypertension, verapamil decreased cardiac output by 30% (p less than 0.01) without appreciably altering pulmonary arterial pressure; thus pulmonary vascular resistance increased slightly (4.9 +/- 0.6 to 6.4 +/- 1.0 mm Hg/liter/min, difference not significant [NS]). Nifedipine decreased hypoxic pulmonary vascular resistance to normoxic values (p less than 0.01). Cardiac output increased 71% while pulmonary arterial pressure remained unchanged. Diltiazem administration produced no change in hypoxic pulmonary hemodynamic variables. The responses to diltiazem, nifedipine, and verapamil during acute pulmonary vasoconstriction induced by PGF2 alpha were similar to those induced by hypoxia. After verapamil, pulmonary vascular resistance tended to increase (7.3 +/- 1.3 to 8.1 +/- 1.4 mm Hg/liter/min, NS). Nifedipine, however, completely blocked pulmonary vasoconstriction by decreasing pulmonary vascular resistance to pre-PGF2 alpha levels (p less than 0.01). This was accompanied by a 157% increase in cardiac output and only a small increase in pulmonary arterial pressure (7 mm Hg). Again, diltiazem produced no change in pulmonary hemodynamic variables. In these acute studies, nifedipine appeared to be a more effective pulmonary vasodilator than verapamil or diltiazem.

Animals↗