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[Role of the TRF test in the study of atrial dysrhythmia].

The aim of this retrospective study of 43 patients (32 females) aged 26 to 84 years old (mean 62 +/- 14,5) was to assess the value of the TRF test in cases with normal static endocrine levels and isolated arrhythmias: 25 atrial fibrillations, 3 atrial flutters, 10 sinus tachycardias, 2 junctional tachycardias, 2 focal atrial tachycardias and 1 atrial extrasystoles. There was underlying cardiac disease in 24 patients. Thyroid function was assessed by T4, T3 and the TRF test. There was no relationship between cardiac disease and arrhythmias with the levels of TSH 25 minutes after TRF. The reactivity to TRF was low: 5,8 +/- 5,6 microU/ml. Nineteen patients were hyperthyroid (TSH at O and 25 min: 1,7 +/- 0,5 and 2 +/- 1 microU/ml respectively), in the following three eventualities: - Clinical hyperthyroidism and raised hormonal levels, the TRF confirmed the diagnosis in 10 out of 11 cases; - Clinical hyperthyroidism and normal hormone levels: the TRF confirmed the diagnosis in 8 out of 14 cases; - Normal clinical examination and normal hormone levels: the TRF test showed a hyperthyroid reaction in 1 out of 18 cases. T3 and T4 measurements are often misleading. The TRF test with 2 blood samples would appear to be essential, especially in patients over 60 years of age. The hyperthyroid population was older (68,5 +/- 8 years) and the mean values of the thyroid investigations (T3, T4 and STH at 25 minutes) were significant. Underlying cardiac disease was detected in over half these cases. Atrial fibrillation was the commonest arrhythmia. Each case of arrhythmia, whether or not related to hyperthyroidism, justifies echocardiography.

Adult↗

Brain TRF immunoreactivity during various physiological and stress conditions in the rat.

Methanol extracts of several rat tissues (hypothalamus, amygdala, the rest of the forebrain, brain stem and pancreas) were partially purified in SP-cation exchange chromatography and measured in TRF radioimmunoassay. It was found that hypothalamic and amygdaloid TRF contents were highest during the light period of the day, but brain stem TRF had an opposite rhythm. Hypothalamic TRF content rose after 10 min by 14% (p less than 0.05) when the rats were exposed to transfer stress. During short-time immobilization stress tests, hypothalamic TRF rose by 41% (p less than 0.05) after a 10-sec immobilization. Cold exposure did not produce any changes in hypothalamic TRF contents within 45 min. Handling stress and time of day appear to be the most important factors influencing the hypothalamic TRF content and have to be taken into account when measuring TRF.

Animals↗

Synergistic effect of tocotrienol-rich fraction (TRF(25)) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans.

Tocotrienols exert hypocholesterolemic action in humans and animals. Lovastatin is widely used for that purpose. Both agents work by suppressing the activity of beta-hydroxy-beta-methylglutaryl coenzyme A reductase through different mechanisms, post-transcriptional vs competitive inhibition. A human study with 28 hypercholesterolemic subjects was carried out in 5 phases of 35 days each, to check the efficacy of tocotrienol-rich fraction (TRF(25)) of rice bran alone and in combination with lovastatin. After placing subjects on the American Heart Association (AHA) Step-1 diet (phase II), the subjects were divided into two groups, A and B. The AHA Step-1 diet was continued in combination with other treatments during phases III to V. Group A subjects were given 10 mg lovastatin, 10 mg lovastatin plus 50 mg TRF(25), 10 mg lovastatin plus 50 mg alpha-tocopherol per day, in the third, fourth, and fifth phases, respectively. Group B subjects were treated exactly to the same protocol except that in the third phase, they were given 50 mg TRF(25) instead of lovastatin.The TRF(25) or lovastatin plus AHA Step-1 diet effectively lower serum total cholesterol (14%, 13%) and LDL-cholesterol (18%, 15% P < 0.001), respectively, in hypercholesterolemic subjects. The combination of TRF(25) and lovastatin plus AHA Step-1 diet significantly reduces of these lipid parameters of 20% and 25% (P < 0.001) in these subjects. Substitution of TRF(25) with alpha-tocopherol produces insignificant changes when given with lovastatin. Especially significant is the increase in the HDL/LDL ratio to 46% in group (A) and 53% (P < 0.002) in group (B). These results are consistent with the synergistic effect of these two agents. None of the subjects reported any side-effects throughout the study of 25-weeks. In the present study, the increased effectiveness of low doses of tocotrienols (TRF(25)) as hypocholesterolemic agents might be due to a minimum conversion to alpha-tocopherol. The report also describes in vivo the conversion of gamma-[4-3H]-, and [14C]-desmethyl (d-P(21)-T3) tocotrienols to alpha-tocopherol.

Journal Article↗

Immunological and biological characteristics of a new TRF analogue, L-pyroglutamyl-L-histidyl-L-pipecolic acid amide.

The immunological and biological potencies of a new synthetic TRF analogue, L-pyroglutamyl-L-histidyl-L-pipecolic acid amide, were compared with those of TRF. In a radioimmunoassay system for TRF, parallel inhibition curves were obtained with TRF and the analogue, the immunological potency of the latter being approximately 50 per cent of the former. In vitro and in vivo TSH-releasing activities of the analogue were almost equal to those of TRF. As was observed with TRF, the in vitro TSH-releasing effect of the analogue was reduced in the presence of T4, and the analogue was inactivated by incubation with rat serum. The data suggest that the pyrrolidine ring of TRF can be replaced with piperidine ring without significant loss of the biological activity.

Animals↗

The requirement for esterase activation in T cell replacing factor (TRF)-induced IgG production in a human B blastoid cell line.

Involvement of stimulus-activatable serine esterase in the process of TRF-induced IgG production in a human B blastoid cell line (CESS) was demonstrated. Addition of DFP or PMSF (1 X 10(-3) M to 1 X 10(-5) M) showed a dose-dependent inhibitory effect on TRF-induced IgG induction in CESS cells. Other organophosphorous inhibitors, such as p-NPEPP and PEPP, were also effective, but a nonphosphorylating analogue of DFP, DMP, was not inhibitory. Simultaneous addition of DFP with TRF showed the inhibitory effect, and the inhibition was irreversible. However, pretreatment of the cells with DFP did not abrogate TRF-induced IgG production. In synchronized cells, signals provided by TRF could be transduced only when cells were in the G1-phase, and DFP showed an inhibitory effect only when it was added to cells in the G1-phase with TRF. One amino acid derivative (AAME) partially inhibited TRF-induced IgG production.

Adenosine Monophosphate↗

Comparison of TRF, propranolol-glucagon, insulin and glucose stimulation tests in acromegaly.

In 7 acromegalic patients growth hormone responses were studied following administration of synthetic TRF, propranolol-glucagon, insulin, and glucose p.o. Except for the glucose tolerance test, a good reproducibility of the STH response was observed. In 5 out of the 7 patients, there was a distinct rise in the plasma STH level after TRF. All patients with a positive insulin tolerance test responded to TRF, as did the two late responders to glucagon; the early responder to the latter test did not respond to TRF. It has been suggested (Liuzzi et al. 1974a) that TRF might be used as a screening test for detecting hypothalamic dependency of the acromegaly. This study suggests that further study is required before accepting this hypothesis and that a response to a combination of tests (TRF, glucagon, insulin) might be a better screening method.

Acromegaly↗

T cell replacing factor for steroids (TRF-S): a 40,000 dalton protein produced by a T4+ T cell.

The induction of polyclonal immunoglobulin (Ig) synthesis by glucocorticosteroids (GCS) in human peripheral blood lymphocytes is dependent on both T cells and monocytes. T cells can be replaced by a cytokine, T cell replacing factor for steroids (TRF-S), which promotes GCS-induced Ig production. T cells produce the cytokine when cultured with intact monocytes, with 24 hr monocyte supernatants, or with small quantities (0.1 U/ml or more) of highly purified interleukin 1 (IL 1). TRF-S was produced by isolated T4+ cells, whereas isolated T8+ cells were unable to help GCS-induced Ig synthesis. High pressure liquid chromatography with a gel permeation column revealed a single locus of activity that corresponded to an apparent m.w. of 40,000. At the dilutions utilized in culture, supernatants containing optimal TRF-S activity (3 U/ml final concentration in culture) were found to have less than 0.2 U/ml (final concentration) of interleukin 2 (IL 2) activity. Neither recombinant IL 2 nor recombinant interferon-gamma (IFN-gamma) over a broad range of concentrations was able to reproduce the capacity of TRF-S to induce the development of Ig-secreting cells with GCS. Thus, we report that TRF-S is synthesized primarily by T4+ T cells, and that its production is stimulated by small concentrations of IL 1. The apparent m.w. of TRF-S is 40,000, and its biological activity is distinct from that of IL 1, IL 2, and IFN-gamma.

Adult↗

Transcription properties of a cell type-specific TATA-binding protein, TRF.

Eukaryotic cells are thought to contain a single TATA-binding protein (TBP) that directs transcription by cellular RNA polymerases. Here we report a cell type-specific TBP-related factor (TRF) that can form a stable TRF/IIA/IIB TATA DNA complex and substitute for TBP in directing RNA polymerase II transcription in vitro. Transfection studies reveal that TRF can differentially mediate activation by some enhancer proteins but not others. Like TBP, TRF forms a stable complex containing multiple novel subunits, nTAFs. Antibody staining of embryos and polytene chromosomes reveals cell type-specific expression and gene-selective properties consistent with the shaker/male sterile phenotype of trf mutants. These findings suggest TRF is a homolog of TBP that functions to direct tissue- and gene-specific transcription.

Animals↗

Clinical significance of telomerase activation and telomeric restriction fragment (TRF) in cervical cancer.

Telomerase activation was examined in 50 cases of cervical cancer, 27 normal cervix and five cervical cancer cell lines using the sensitive polymerase chain reaction (PCR)-based TRAP (telomeric repeat amplification protocol) assay. Telomeric restriction fragment (TRF) length of these specimens was measured by Southern hybridisation. Telomerase activation was common in cervical cancers and was detected in 46/50 cases (92%). Telomerase activity was weak in normal cervix and was detected only in 2/27 cases (7.4%). Telomerase activity was detected in all stages of cervical cancer suggesting that it is an early event in cancer progression. The clinical significance of telomerase activation was analysed in 47 squamous cell carcinoma of the cervix. High telomerase activity was more frequently detected in advanced diseases (100% in stage III and stage IV cervical cancers combined) compared with early diseases (68.6% in stage I and stage II cancers combined). The difference was statistically significant (P < 0.02). Telomerase activity was not statistically correlated with other clinical parameters examined. This is the first report of telomeric length in human cervical cancer. Both shortening and elongation of TRF length in cervical cancers was observed. Advanced cervical cancers tended to have a wider range of variation of TRF length compared with early disease and normal cervix. There was no obvious relationship between TRF length and the clinical parameters examined including clinical staging, differentiation status of tumour, human papilloma virus (HPV) infection, recurrence rate, tumour size and invasion depth. The clinical significance of TRF length appears to be limited in cervical cancers. Our results indicate that telomerase activity is closely associated with tumour cells and may be useful as a marker for detection of tumour cells in cervical biopsies.

Adenocarcinoma↗

[Emotional and behavioral disorders at preschool age--results of a study in kindergarten children in Dortmund using the Caregiver-Teacher Report Form C-TRF/1 1/2-5].

OBJECTIVES: Currently there is a lack of screening instruments suitable for use by preschool and kindergarten teaches to assess behavioural and emotional problems in preschool children. The C-TRF/1 1/2-5 (Caregiver-Teacher Report Form for the ages 1 1/2-5) is a screening instrument designed by Achenbach to assess behavioural and emotional problems in this age group. In a joint project of the Fachhochschule Dortmund and the Department of Child and Adolescent Psychiatry, University of Ulm, in cooperation with the Youth Welfare Office Dortmund, the C-TRF/1 1/2-5 was used to assess the prevalence of psychological disturbance among kindergarten children. METHODS: 1,050 children aged 3-6 years from 46 kindergartens from the greater Dortmund urban area were rated by their caregivers on the basis of the German version of the C-TRF/1 1/2-5. RESULTS: The reliability of C-TRF/1 1/2-5 proved to be good-to-sufficient, with internal consistencies ranging from .94 to .58. The number of behavioural and emotional problems, which is very close to that found among American preschool children, decreases with age and more strongly so among girls. The externalizing problems among boys do not decrease much, but remain quite stable from age 3 to age 6. The prevalence of internalizing problems among preschool boys and girls does not differ. CONCLUSIONS: The German version of the C-TRF/1 1/2-5 proved to be an instrument sufficiently reliable for screening behavioural and emotional problems in preschool children. The prevalence of these psychological problems among German and American children is very similar.

Affective Symptoms↗

Test-retest reliability and criterion validity of the Chinese version of CBCL, TRF, and YSR.

BACKGROUND: Psychometric properties of the Chinese version of CBCL, TRF, and YSR were understudied. This study aimed at examining their test-retest reliability and criterion validity. METHODS: Three Chinese community and clinic samples were recruited in Hong Kong. The parents, teachers, and youths respectively completed the CBCL, TRF, and YSR. RESULTS: The Chinese CBCL, TRF, and YSR were test-retest reliable and valid. However, there was score/case attenuation at retest. CBCL and TRF appeared to screen externalizing and ADHD problems better, while YSR screened internalizing problems better. CONCLUSIONS: Clinicians should be cautious about score/case attenuation at retest while using CBCL, TRF, and YSR to chart patients' progress. They should also recognize their different strengths in screening various disorders.

Adolescent↗

Degradation of TRF immunoreactivity in rat hypothalamus, extrahypothalamic brain and pancreas.

The endogenous TRF as measured in radioimmunoassays of chromatographically purified extracts of excised hypothalami, extrahypothalamic brains and pancreas was shown to be stable in intact organs and homogenates. However, synthetic TRF added to tissue homogenates was degraded. Sonication of the homogenates liberated endogenous TRF for degradation. Chromatographically purified tissue extracts of hypothalamus, extrahypothalamic brain and pancreas were degraded similarly by rat serum. These results suggest that the major portion of endogenous TRF occurs in a protected form in tissues and hence the physiologically effective amount of TRF must be very low when compared to its total content in tissues.

Animals↗

Soluble factors involved in B cell differentiation: identification of two distinct T cell-replacing factors (TRF).

Highly purified B lymphocytes cultured with affinity-purified goat anti-mouse IgM antibodies and B cell growth factor (BCGF) proliferate but fail to differentiate into immunoglobulin-synthesizing cells during 4-day cultures. Induction of immunoglobulin (Ig) synthesis depends on the presence of two additional T cell-derived factors (T cell-replacing factors [TRF]). One TRF, designated B15 1K 12-TRF, is found in the supernatant of B15 1K 12 T hybridoma cells. It is required relatively early in these cultures and appears to cause an increase in cell yield as well as Ig synthesis. The second factor, designated EL-TRF, is found in PMA-induced EL-4 supernatant. It appears to be different from both BCGF and IL 2 in that it can be separated from the former by isoelectric focusing and from the latter by phenyl-Sepharose chromatography. EL-TRF is still active if added on the last day of a 4-day culture. A model for the action of anti-IgM and these three T cell-derived factors in B cell activation and differentiation is proposed.

Animals↗

Prepubertal and young adolescent bipolarity versus ADHD: assessment and validity using the WASH-U-KSADS, CBCL and TRF.

BACKGROUND: This addendum to 'Prepubertal and early adolescent bipolarity differentiate from ADHD by mania criteria; grandiose delusions; ultra-rapid or ultradian cycling' (in this volume) provides (1) a description of Washington University at St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with sample sections (hypersexuality, rapid cycling); (2) a comparison of WASH-U-KSADS to KSADS-P/L and KSADS-1986 and (3) a comparison of WASH-U-KSADS to Child Behavior Checklist (CBCL) and Teachers Report Form (TRF) data. METHODS: Data were from the first 60 bipolar (BP) and first 60 ADHD subjects of 270 consecutively ascertained cases (90 BP, 90 ADHD and 90 community controls) in the NIMH funded 'Phenomenology and Course of Pediatric Bipolarity' study. Comprehensive assessments included the WASH-U-KSADS (administered blindly to mothers and separately to children), CBCL and TRF. RESULTS: As reported elsewhere in this volume, WASH-U-KSADS data significantly differentiated BP and ADHD groups. Significant differences were also found with the parent-rated CBCL and the teacher-rated TRF, thereby providing cross-modality and cross-informant validation of the WASH-U-KSADS. Because of the close agreement with published CBCL data from another investigator, cross-site validation also occurred. LIMITATIONS: Venues for consecutive ascertainment from the lowest socioeconomic status classes were unavailable due to current health care policies. CLINICAL RELEVANCE: CBCL and TRF data separated BP from ADHD groups, largely by non-specific externalizing dimensions (e.g., hyperactivity, aggressivity). Clinically relevant differentiation by categorical mania-specific criteria (e.g., elated mood, grandiosity, racing thoughts) occurred with WASH-U-KSADS data. Both types of data are crucial for genetic and neurobiological studies.

Adolescent↗

The number of the Trf receptors on human hematopoietic cell lines is influenced by membrane phospholipids.

The effect of phospholipases and of inhibitors of phospholipases on the binding of 125I-Trf to human hematopoietic cell lines was investigated. The results showed that incubation of the cells with phospholipases or inhibitors of phospholipases elicited a significant reduction of the Trf binding. This phenomenon was related to a reduction of Trf binding sites without affecting the affinity of the receptors for Trf. These results suggest that the phospholipids of the cell membrane may modulate the binding of transferrin to its receptor.

Acetophenones↗

Selective elimination of a B cell subset having acceptor site(s) for T cell-replacing factor (TRF) with biotinylated antibody to the acceptor site(s) and avidin-ricin A-chain conjugate.

A covalent conjugate of avidin with ricin subunit A-chain (avidin-RA) was prepared by using N-succinimidyl 3-(2-pyridyldithio)propionate as a coupling agent. Selective cytotoxic activity after the combined treatment of spleen cells with biotinylated antibody and avidin-RA was demonstrated by the fact that the responsiveness to LPS was selectively abrogated by pretreatment of the cells with biotinylated rabbit anti-mouse immunoglobulin (MIg) antibody, but not with biotinylated anti-Thy-1.2 antibody. Neither the biotinylated antibody alone nor avidin-RA alone was effective in decreasing the responses to mitogens. Moreover, a high anti-DNP PFC response elicited by DNP-KLH-primed BALB/c mouse spleen cells stimulated in vitro with DNP-KLH was mostly abrogated by the pretreatment of the cells with biotinylated anti-MIg antibody and avidin-RA. Again, neither the biotinylated antibody alone nor avidin-RA alone was effective in decreasing the anti-DNP PFC response. This cell-killing method with the use of biotinylated antibody and avidin-RA was applied and evaluated in experimental systems in which the helper action of T cells on B cells was mediated by T cell-replacing factor (TRF) or was performed by the direct interaction of T cells with B cells (cognate interaction). When DNP-KLH-primed splenic B cells, pretreated with biotinylated F(ab')2 fragment of DCF1 male anti-BALB/c-B IgG antibody against acceptor site(s) for TRF followed by treatment with avidin-RA, were stimulated with DNP-OVA in the presence of monoclonal TRF, the anti-DNP PFC response was significantly decreased, whereas the same treated B cells responded well to stimulation with DNP-PPD in the presence of Tbc-primed T cells (cognate interaction). These results indicate that B cells responsible for the cognate interaction and those having TRF acceptor site(s) belong to a distinct subpopulation of B cells, and that the cytocidal action of the noncovalent conjugate of the antibody and RA formed from the biotinylated antibody and avidin-RA via an avidin-biotin complex has immunologic selectivity, eliminating only the latter subset of B cells recognized by the antibody.

Animals↗

T cells produce TRF in response to Con A and factors in T cell hybridoma supernatants.

In recent experiments, a soluble factor (TRF) that mediates the differentiation of anti-immunoglobulin (Ig)-activated B cells to Ig-secreting cells has been identified. TRF works in concert with a growth factor, probably IL 2, in the induction of activated B cells. In previous studies, TRF was identified in culture supernatants of activated T cells and accessory cells, and thus the cellular source (T cell or accessory cell) of the factor was not determined. In the present studies, we succeeded in inducing the production of TRF by T cell populations from which accessory cells had been vigorously depleted. Lymph node cells were depleted of accessory cells by nylon wool adherence and anti-Ia and complement treatment; these cells were activated with Con A and a T cell hybridoma supernatant that contains IL 2. Supernatants from these activated T cell cultures supported the differentiation of anti-Ig-activated B cells to Ig secreting cells. These results show that T cells produce the differentiation factor, and further that they do so in response to ligand (Con A) plus a T cell-derived factor.

Animals↗

Preliminary chemical and biologic characterization of (Fc)TRF: an Fc fragment-induced T cell-replacing factor.

Fc fragment stimulation of Lyt-1+2- T lymphocytes triggers release of a T cell-replacing factor, here called (Fc)TRF. Chemical and biologic characterization of (Fc)TRF has been undertaken to provide information for its comparison with other T cell factors. Preliminary chemical characterization by column chromatography and isoelectric focusing suggest (Fc)TRF activity resides in a class of acidic molecules that fall into two size classes of 58-60,000 daltons and 35-40,000 daltons. This factor is distinct from Interleukin 2 (IL 2) as it has no T cell growth-promoting or costimulator activity, although it can also be generated by Con A activation of murine spleen cells. By these results (Fc)TRF has been defined as a unique T cell-replacing activity that promotes differentiation of B lymphocytes to antibody-secreting cells.

Animals↗