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Biomedical subjects

T Turner

Publications and source records attributed to T Turner.

At least 37 records · Page 2Linked to original sources

Release of the neuronal glycoprotein ICAM-5 in serum after hypoxic-ischemic injury.

Intercellular adhesion molecule (ICAM)-5 (telencephalin) is unique among the ICAMs, because it is only expressed in somatodendritic membranes of telencephalic neurons. To investigate the fate of ICAM-5 during focal brain injury, we induced hypoxia-ischemia (HI) damage in adult mice by right common carotid artery ligation followed by hypoxia. ICAM-5 was detectable in serum within a 48-hour window after HI injury. In HI brain, dendritic ICAM-5 immunore-activity was abolished, but it was present in the neuropil and soma of hippocampal pyramidal, dentate granule, and some cortical and striatal neurons. After HI injury, levels of ICAM-5 protein and messenger RNA initially increased, and ICAM-5 messenger RNA expression then decreased, although protein levels continued to increase. Because HI injury induces microglial activation with increases in CD11a/CD18 (lymphocyte function antigen [LFA]-1) counterreceptors to ICAM-5, we investigated whether modulation of interactions between LFA-1 receptors and brain ICAM-5 during HI injury are associated with changes in levels of serum ICAM-5. Intracerebroventricular administration of lipopolysaccharide to activate microglia before HI injury resulted in elevated serum ICAM-5 levels compared with those in mice with only HI injury. Pretreatment with anti-LFA-1 antibodies before HI injury or LFA-1 receptor knockout mice with HI injury had markedly reduced levels of serum ICAM-5. Lipopolysaccharide levels increased, whereas LFA-1 receptor blockade or LFA-1 knockout decreased HI injury in the first 12 hours. These data suggest that during the necrotic phase of HI injury, serum ICAM-5 may be a potential marker for somatodendritic neuronal damage.

Animals↗

Immune rejection of intracerebral gliomas using lymphocytes from glioma-bearing rats.

Naturally occurring malignancies do not induce immune responses against cancer antigens. Is the lack of an immune response caused by an antigen presentation defect or by induced antigen-specific immune suppression? The current study was performed to determine whether a progressing intracerebral malignancy affects production of peripheral autologous glioma antigen-specific immune responses. Peripheral immunization of both glioma-bearing and non-glioma-bearing animals with cancer cells and adjuvant generated similar levels of glioma antigen-specific cytotoxic T lymphocyte activity. However, immune cell populations from glioma bearers were significantly less efficient than immune cell populations from non-cancer bearers in their ability to reject progressing intracerebral tumors. A variety of manipulations designed to reduce nonspecific immune suppression in vivo and in vitro had no effect on the in vivo efficacy of the activated T-lymphocyte populations. The presence of progressing tumors appeared to augment rather than suppress cancer antigen-specific responses, leading to the speculation that reduced efficacy was caused not by generalized immune suppression but rather by a reduction in the number of immune effector cells by either clonal anergy or clonal deletion. Most importantly, the data demonstrated that, despite decreased in vivo efficacy, immune effector cells capable of rejecting an intracerebral malignancy could be generated from cancerous hosts.

Animals↗

Effectiveness of cognitive therapy for delusions in routine clinical practice.

BACKGROUND: Previous studies have suggested that cognitive therapy is effective in modifying delusions. AIMS: To assess the effectiveness of cognitive therapy on patients seen in routine clinical work. METHOD: Eighteen patients with chronic delusions were treated using cognitive therapy, after the method of Chadwick and Lowe. A single-case multiple-baseline experimental design was used, including a control treatment. Each subject was used as their own control. RESULTS: Six patients reduced conviction in their delusions during cognitive therapy and not during the control treatment. Seven patients' conviction ratings did not change. Five patients showed a variable response. Degree of conviction did not fall to zero in any patient. All patients reported that the therapy had been helpful; six spontaneously mentioned changes in psychotic thinking. CONCLUSIONS: One-third of patients with chronic delusions whom we treated responded to delusion modification with a reduction in degree of belief. Change within therapy sessions predicted outcome, as did variation in the conviction during baseline. Cognitive therapy with delusions should aim at reducing distress as well as conviction.

Case-Control Studies↗

EGF receptor signaling in prostate morphogenesis and tumorigenesis.

The growth and differentiation of the prostate gland are largely dependent on extracellular signaling factors. In addition to androgens, many polypeptide growth factors function through autocrine or paracrine networks. The paracrine interaction between stromal and epithelial cells is critical for androgen regulation, morphogenesis, epithelial cell proliferation, and secretory differentiation. Efforts to identify the essential growth factors and studies on their effects have been prompted by the fact that prostate cells in culture need substances other than androgens for proliferation. In this context, transforming growth factor-alpha and epidermal growth factor, among others, have been studied extensively. Recent advances have suggested that these EGF receptor (EGFR) ligands play roles not only during glandular development but also during neoplastic transformation and tumor progression. The cell responses most relevant to the role of this receptor signaling are both mitogenesis and cell motility. The aim of the review is to provide an overview of current knowledge about EGFR and its ligands in the organogenesis and tumorigenesis of the prostate gland.

Animals↗

Mapping of the ICAM-5 (telencephalin) gene, a neuronal member of the ICAM family, to a location between ICAM-1 and ICAM-3 on human chromosome 19p13.2.

Intercellular adhesion molecule 5 (ICAM-5, telencephalin) is a cell adhesion molecule expressed on neurons in the most rostral segment of the mammalian brain, the telencephalon. Antibody studies in rodents and rabbits have demonstrated expression of this molecule on the cell body and dendrites of these neurons. We have examined the expression pattern in human brain by Northern blot analysis of 16 human brain segments. This analysis has confirmed the unique expression pattern of this ICAM in human. In addition, we report the mapping of the human ICAM-5 gene to an 80-kb region on chromosome 19p13.2 that also contains ICAM-1 and ICAM-3.

Antigens, CD↗

Treatment of human prostate cancer cells with dolastatin 10, a peptide isolated from a marine shell-less mollusc.

BACKGROUND: Dolastatin 10 is an anticancer peptide isolated from the sea hare, Dolabela auricularia, which is currently in phase I trials. METHODS: The effects of dolastatin 10 on the DU-145 human prostate cancer cell line were studied both in tissue culture and in athymic nude mice. In tissue culture, after dolastatin 10 treatment, cell cycle kinetics were measured using propidum iodide, apoptosis was estimated using the TUNEL assay, and tubulin architecture studied by direct immunofluorescence. RESULTS: At concentrations of 1 nM (IC50 = 0.5 nM), dolastatin 10 completely inhibited the growth in tissue culture of human prostate cancer DU-145 cells. Growth inhibition was correlated with the arrest of these cells in G2/M and alpha-tubulin depolymerization. In athymic mice at a dose of 5 micrograms every 4 days i.p., dolastatin 10 blocked the diaphragmatic invasion of DU-145 tumor cells. CONCLUSIONS: Dolastatin 10 is a novel marine-derived compound with activity in the treatment of human prostate cancer in animals. The mechanism of action of this agent involves tubulin depolymerization but not the induction of apoptosis.

Animals↗

Regiospecific expression of cytochrome P4501A1 and 1B1 in human uterine tissue.

The goal of this study was to investigate the expression of these isoforms in different regions of the human uterus. Expression was determined in the endometrium (ENDO), endocervix (CERV) and squamous region (SR) from six non-smoking women by using RT-PCR. The transcripts encoding for CYP1A1 were significantly higher (P < 0.05) in the SR compared to the other areas. However, the expression of CYP1B1 was significantly higher (P < 0.05) in the ENDO. CYP1B1 expression appeared to be extremely low in a woman in the secretory stage of the menstrual phase, relative to the ENDO of the other patients who were all in the proliferative stage at hysterectomy. CYP1B1 mRNA was expressed in only two out of six patients in the SR and in three out of five patients in the CERV. CYP1A1 was also uniformly expressed in the ENDO of all except one patient, whereas expression was minimal in the other regions. It is likely that variability in the expression of these isoforms may be responsible for the differential susceptibility to cancer in women.

Adult↗

The effects of endurance exercise training on ambulatory blood pressure in normotensive older adults.

This study investigated the effects of 16-weeks of endurance exercise training (EET) on ambulatory blood pressure in older adults. Twenty-one men and women, 68.5 +/- 4.7 (mean +/- SD) years of age were randomly assigned to an exercise group (EG, n = 11) or to a control group (CG, n = 10). Subjects were normotensive (mean resting BP 132.0 +/- 8.6/80.1 +/- 6.6 mm Hg), free from overt cardiovascular or renal diseases, and were taking no vasoactive or diuretic medications. Maximal oxygen uptake (VO2max), body composition, resting BP, and 24-hr ambulatory systolic (ASBP) and diastolic (ADBP) blood pressures were measured in all subjects before and after the study period. The EG completed 16 weeks (3, 1-hour bouts/wk) of EET, progressing in intensity from 50% to 85% of maximal workload. The CG did not exercise. In the EG, although body composition and resting BP did not change (p > 0.05), VO2max increased by 14% (p = 0.001), mean 24-hr ASBP decreased 7.9 mm Hg (p = 0.0001), and mean 24-hr ADBP decreased 3.6 mm Hg (p = 0.002). In the CG, there were no significant changes in these variables (p > 0.05). These data suggest that EET can improve both aerobic fitness and "real-life" blood pressures in healthy older adults and may help inhibit increases in blood pressure associated with normal aging.

Aged↗

Intrauterine growth and ultrasound findings in fetuses with Beckwith-Wiedemann syndrome.

OBJECTIVE: To assess intrauterine growth in a series of nine fetuses diagnosed with Beckwith-Wiedemann syndrome. METHODS: Infants confirmed postnatally to have Beckwith-Wiedemann syndrome were identified from records maintained in the Division of Clinical Genetics. Antenatal ultrasound and birth records were evaluated. Head circumference (HC), abdominal circumference (AC), and estimated fetal weight (EFW) were assigned percentiles based on gestational age. Newborn HC and birth weight were also assigned percentiles. Polyhydramnios was diagnosed using either amniotic fluid index or documented subjective assessment. RESULTS: Nine infants with Beckwith-Wiedemann syndrome had antenatal ultrasound examinations. Seven of these had more than one examination. Two infants were suspected to have Beckwith-Wiedemann syndrome in utero. Important ultrasound findings included omphalocele (four), enlarged liver and kidneys (one), and enlarged liver (one). Fetal tongue protrusion on ultrasound was not identified in any fetus. Six of nine fetuses (66%) with ultrasound examinations after 25 weeks' gestation had polyhydramnios. Evaluation of the fetal HC, AC, and EFW percentiles demonstrated that fetuses with Beckwith-Wiedemann syndrome may exhibit accelerated growth as early as 25-30 weeks' gestation, but may exceed the 90th percentile only after 36 weeks' gestation. CONCLUSIONS: Fetuses with omphalocele, polyhydramnios, and an AC less than the 90th percentile may have Beckwith-Wiedemann syndrome. Polyhydramnios and accelerated growth beginning between 25 and 36 weeks' gestation, even without omphalocele, should alert the physician to the possibility of Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann Syndrome↗

Maternal, paternal, and marital functioning in families of preadolescents with spina bifida.

Based on a family systems/social-ecological perspective, mothers and fathers of 8- and 9-year-old children with spina bifida (n = 55; 28 male, 27 female) were examined in comparison to a matched group of parents with 8- and 9-year-old able-bodied children (n = 55; 29 male, 26 female) across several areas of functioning (individual, parental, and marital). Findings suggested that mothers and fathers in the spina bifida sample tended to report more psychosocial stress than their counterparts in the able-bodied sample. Specifically, mothers and fathers in the spina bifida group reported less parental satisfaction than parents in the able-bodied group. Mothers in the spina bifida group reported less perceived parental competence, more social isolation, and less adaptability to change; fathers in the spina bifida group reported more psychological symptoms. No differences between the spina bifida and able-bodied groups were found with respect to marital satisfaction. Coping predictors of adjustment tended to vary as a function of parent gender rather than group status.

Adaptation, Psychological↗

Sharing psychiatric care with primary care physicians: the Toronto Doctors Hospital experience (1991-1995).

OBJECTIVES: To investigate the shared mental health care experience of the psychiatry department of a small urban general hospital, which serves an ethnoculturally diverse population. METHODS: A chart survey was undertaken of all patients referred by community physicians to a new shared care program between January 1991 and December 1995. Selected demographic and diagnostic characteristics were collected and analyzed. RESULTS: Seven hundred and thirteen patients were assessed. They were principally female, ethnoculturally varied, and highly comorbid. The most striking association involved mood and substance-related disorders. CONCLUSION: The Doctors Hospital experience shows that the shared care approach can reach large numbers of patients through a multiplier effect. Additionally, this approach has the potential to enhance access for ethnoculturally varied and diagnostically complex groups.

Ambulatory Care↗