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PubMed2006

Postprandial metabolic fate of tocotrienol-rich vitamin E differs significantly from that of alpha-tocopherol.

BACKGROUND: The detection of tocotrienols in human plasma has proven elusive, and it is hypothesized that they are rapidly assimilated and redistributed in various mammalian tissues. OBJECTIVE: The primary study objective was to evaluate the postprandial fate of tocotrienols and alpha-tocopherol in human plasma and lipoproteins. DESIGN: Seven healthy volunteers (4 males, 3 females) were administered a single dose of vitamin E [1011 mg palm tocotrienol-rich fraction (TRF) or 1074 mg alpha-tocopherol] after a 7-d conditioning period with a tocotrienol-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of tocopherol and tocotrienol isomers in plasma, triacylglycerol-rich particles (TRPs), LDLs, and HDLs were measured at each interval. RESULTS: After intervention with TRF, plasma tocotrienols peaked at 4 h (4.79 +/- 1.2 microg/mL), whereas alpha-tocopherol peaked at 6 h (13.46 +/- 1.68 microg/mL). Although tocotrienols were similarly detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly lower than alpha-tocopherol concentrations. In comparison, plasma alpha-tocopherol peaked at 8 h (24.3 +/- 5.22 microg/mL) during the alpha-tocopherol treatment and emerged as the major vitamin E isomer detected in plasma and lipoproteins during both the TRF and the alpha-tocopherol treatments. CONCLUSIONS: Tocotrienols are detected in postprandial plasma, albeit in significantly lower concentrations than is alpha-tocopherol. This finding confirms previous observations that, in the fasted state, tocotrienols are not detected in plasma. Tocotrienol transport in lipoproteins appears to follow complex biochemically mediated pathways within the lipoprotein cascade.

Adult↗
PubMed1984

Ultrastructural markers of lymph nodes in patients with acquired immune deficiency syndrome and in homosexual males with unexplained persistent lymphadenopathy. A quantitative study.

To determine if vesicular rosettes (VR), tubuloreticular structures (TRS), and "test-tube and ring-shaped forms" (TRF) are characteristic ultrastructural features of the syndromes of acquired immune deficiency (AIDS) or of unexplained persistent lymphadenopathy (PLS), the authors studied lymph nodes from nine patients with PLS, two patients with AIDS, and seven controls by electron microscopy. An average of 122 lymphocytes per case were photographed. VR were present in only 0.37% of lymphocytes in 4 of 11 index cases and were mimicked by grouped vesicles and degenerating multivesicular bodies (MVB). TRS were found in 10 of 11 index cases, compared with only one of seven controls (P less than 0.01). In the index cases, they were more frequent in AIDS (mean 21%) than in PLS lymphocytes (mean 4%) (P less than 0.05). MVB were found in all index cases and five of seven controls and were more frequent in index lymphocytes (mean 19%) than in controls (mean 5%) (P less than 0.01). TRF were found in one Haitian male with AIDS, where they were present in 4% of lymphocytes. VR are infrequent and indistinct. MVB probably reflect the reactivity of the lymphocytes. TRF is not a feature of PLS. The authors conclude that there are no pathognomonic ultrastructural markers of AIDS or PLS but that TRS are characteristic of both syndromes and occur frequently enough to be supportive to the diagnosis of AIDS and PLS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I.

Despite evidence that DNA topoisomerase I is required to relieve torsional stress during DNA replication and transcription, yeast strains with a top1 null mutation are viable and display no gross defects in DNA or RNA synthesis, possibly because other proteins provide overlapping functions. We isolated mutants whose inviablility or growth defect is relieved when TOP1 is expressed [trf mutants (topoisomerase one-requiring function)]. The TRF genes define at least four complementation groups. TRF3 is allelic to TOP2. TRF1 is allelic to HPR1, previously shown to be homologous to TOP1 over two short regions. TRF4 encodes a novel 584-amino acid protein with homology to the N-terminus of Saccharomyces cerevisiae topo I. Like top1 mutants, trf4 mutants have elevated rDNA recombination and fail to shut off RNA polymerase II transcription in stationary phase. trf4 null mutants are cs for viability, display reduced expression of GAL1 and Cell Cycle Box UAS::LacZ fusions, and are inviable in combination with trfI null mutants, indicating that both proteins may share a common function with DNA topoisomerase I. The existence of multiple TRF complementation groups suggests that not all biological functions of topo I can be carried out by topo II.

Alleles↗
PubMed2001

Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6 ApoE-deficient mice.

We are studying novel tocotrienols, which have a number of activities that might interfere with the formation of atherosclerotic plaques, including hypocholesterolemic, antioxidant, anti-inflammatory and antiproliferation effects. This study compared the effects of alpha-tocopherol, the tocotrienol-rich fraction (TRF(25)) and didesmethyl tocotrienol (d-P(25)-T3) of rice bran on the pathogenesis of atherosclerotic lesions in C57BL/6 apolipoprotein (apo)E-deficient (-/-) mice. These mice are an excellent model because they become hyperlipidemic even when they consume a low fat diet and they develop complex atherosclerotic lesions similar to those of humans. These compounds were also tested in wild-type C57BL/6 apoE (+/+) and (+/-) mice fed low or high fat diets. When a high fat diet was supplemented with alpha-tocopherol, TRF(25) or d-P(25)-T3 and fed to mice (+/+) for 24 wk, atherosclerotic lesion size was reduced 23% (P = 0.33), 36% (P = 0.14) and 57% (P < 0.02), respectively, and in mice (+/-) fed for 18 wk, lesions were reduced by 19% (P = 0.15), 28% (P < 0.01) and 33% (P < 0.005), respectively, compared with mice fed a control diet. A low fat diet did not cause atherosclerotic lesions in these mice. The low fat diet supplemented with TRF(25) or d-P(25)-T3 fed to apoE-deficient (-/-) mice for 14 wk decreased atherosclerotic lesion size by 42% (P < 0.04) and 47% (P < 0.01), respectively, whereas alpha-tocopherol supplementation resulted in only an 11% (P = 0.62) reduction. These results demonstrate the superior efficacy of tocotrienols compared with alpha-tocopherol. Although tocotrienols decreased serum triglycerides, total and LDL cholesterol levels, the decreases in atherosclerotic lesions seem to be due to the other activities. Serum tocol concentrations in various groups are also described. This is the first report of a significant reduction in the atherosclerotic lesion size in all three genotypes of apoE mice fed a novel tocotrienol (d-P(25)-T3) of rice bran. Dietary tocotrienol supplements may provide a unique approach to promoting cardiovascular health.

Analysis of Variance↗
PubMed2001

Clinical impact of differential renal function to indicate and assess pyeloplasty and the significance of coexisting vesicoureteral reflux.

PURPOSE: In patients with ureteropelvic junction obstruction (JPJO) who are conservatively treated, 5% to 10% of them show a deterioration of renal function without recovery after delayed pyeloplasty. Should surgery be indicated based on observed deterioration of differential renal function (DRF)? Can we expect improvement of the DRF after pyeloplasty? What other influencing parameters may affect DRF? MATERIALS AND METHODS: In this study, the authors examined 85 ureterorenal junctions that had undergone the Anderson-Hynes technique for surgical correction of UPJO. Based on the values obtained from the preoperative DRF (Tc-99m mercaptoacetyltriglycine), the cases were separated into three categories: group I had poor DRF (less than 11% of total renal function [TRF]), group II had moderate DRF (11% to 33% of TRF), and group III had adequate DRF (more than 33% of TRF). Twelve months after surgery, renal function was reassessed. The results were correlated with age at surgery, symptoms, coexisting vesicoureteral reflux, and drainage. RESULTS: Seven ureterorenal junctions (8%) comprised group I, 15 (18%) comprised group II, and 63 (74%) comprised group III. After UPJO repair, 13% showed marked improvement in DRF, 86% remained stable, and 1% exhibited diminished function. In 50% of the renal cases with preoperative DRF less than 33%, postoperative improvement was seen. In follow-up renal scans, 30 cases (35%) revealed nonobstructive drainage, whereas the remaining 53 junctions (62%) showed moderate delayed drainage. Both the moderate delayed group (57%) and the nonobstructive group (50%) showed similar DRF improvement. Sixty-six percent of the patients with impaired DRF improved after pyeloplasty performed within the first 3 months of life, compared with 42.8% of patients in whom surgery was performed after 5 years of age. Vesicoureteral reflux was evident in 27.2% of the patients with preoperative impaired DRF compared with 11% with normal DRF. Forty-five percent of the patients with impaired DRF and no improvement after surgery had coexisting vesicoureteral reflux, compared with 9% of those with postoperative improvement. CONCLUSIONS: Sustained renal impairment after pyeloplasty is likely as a result of preexisting renal dysplasia with vesicoureteral reflux. Moderate delayed drainage after surgery does not affect DRF. Surgery for UPJO should be indicated independent of a DRF follow-up (except very low DRF) or the age at the time of diagnosis.

Child↗
PubMed1995

Psychological effects of Hurricane Andrew on an elementary school population.

OBJECTIVE: To explore the prevalence and progression of posttraumatic symptomatology (PTS), using emotional and behavioral indices of psychopathology in school-age children in the pathway of Hurricane Andrew (HI-IMPACT) and in a comparison group north of Miami (LO-IMPACT). METHOD: Pynoos' Posttraumatic Stress Disorder Reaction Index and Achenbach's Teacher's Report Form (TRF) were administered 8 weeks and 32 weeks after the hurricane. In addition, 21 measures of disruptive behavior cataloged by Dade County Public Schools were aggregated and compared by grading period between pre- and posthurricane school years. RESULTS: There were no statistically significant differences between the two schools in PTS at 8 weeks after the hurricane, although the children in the HI-IMPACT school were more likely to have severe PTS. TRF findings at 8 weeks revealed that children in the HI-IMPACT school evidenced lower means on the eight TRF scales and on the broader Internalizing and Externalizing measures. Analysis of the disruptive behavior revealed a drop in the marking period immediately after the hurricane in the HI-IMPACT area, but an opposite effect was observed in the LO-IMPACT area. CONCLUSIONS: After the hurricane there was an initial increase in PTS and a concomitant decrease in other measures of behavior and psychopathology. PTS remained relatively high throughout the school year, but there was a rebound and subsequent normalization of the measures of disruptive behavior.

Child↗
PubMed2001

Behavioral and emotional problems in Chinese adolescents: parent and teacher reports.

OBJECTIVE: This study examined behavioral and emotional problems in Chinese adolescents. METHOD: A sample of 1,694 adolescents aged 12 to 16 years participated in this study in 1997. Parents completed the Child Behavior Checklist (CBCL), and teachers completed the Teacher's Report Form (TRF). RESULTS: For both parent and teacher reports, internalizing syndromes were scored higher in girls and externalizing syndromes were scored higher in boys. Scores on most of the CBCL and TRF subscales were higher for the older adolescents. The overall prevalence rates of parent- and teacher-reported behavioral problems were 23.1% and 19.2%, respectively. The eight cross-informant syndromes were highly comorbid, with a significant association across syndromes (mean odds ratio = 16.1 for CBCL and 22.5 for TRF). Correlations between parent and teacher reports were 0.51 for eight subscales and 0.68 for Total Problems. CONCLUSIONS: These findings demonstrate that behavioral and emotional problems tend to increase with age and cluster in the same individuals. The prevalence rates of behavioral problems in Chinese adolescents are comparable to those reported in Western countries. In contrast to findings for Western samples, parent reports of behavioral problems were highly correlated with teacher reports.

Adolescent↗
PubMed2001

Prevalence of psychopathology in children of a bipolar parent.

OBJECTIVE: To determine psychopathology in adolescent children of a bipolar parent living in the Netherlands, using multiple sources of information (self-, parent, and teacher reports). METHOD: Problem behavior in 140 offspring (aged 12-21 years) of 86 bipolar parents was assessed with the Child Behavior Checklist (CBCL), the Teacher's Report Form (TRF), and the Youth Self-Report (YSR) between 1997 and 1999. All adolescents, bipolar parents, and their available spouses were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). RESULTS: Higher problem scores were found for 8 of the 11 CBCL scales for girls and 4 of the 11 CBCL scales for boys, compared with a Dutch normative sample, and 1 Young Adult Self-Report (YASR) scale for girls compared with an American normative sample. Lower problem scores were found on 4 YSR and 4 YASR scales for boys, 1 TRF scale for girls, and 1 TRF scale for boys. The prevalence of current DSM-IV diagnoses in the offspring was 29% and of life-time DSM-IV diagnoses, 44%. CONCLUSIONS: The prevalence of problem behavior and DSM-IV diagnoses found in our sample did not support the notion that the level of psychopathology in children aged 12 to 21 years of bipolar parents is highly elevated. This study, similar to prior studies, suffers from lack of information on the representativeness of the sample and a rather low response rate.

Adolescent↗
PubMed1999

Comparison of internalizing and externalizing symptoms in children with attention-deficit hyperactivity disorder with and without comorbid tic disorder.

This study examined the relation between internalizing and externalizing symptoms in two groups of prepubertal boys (with and without multiple chronic tic disorder) with diagnosed attention-deficit hyperactivity disorder (ADHD). Parents and teachers completed the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF), respectively. Children were carefully evaluated for the absence of a chronic tic disorder. Boys with ADHD and chronic multiple tic disorder (ADHD/+tics) received significantly higher (p = .0032, Bonferroni correction) scores for the Anxious/Depressed, Thought Problems, and Attention Problem scales of the CBCL and the Delinquent Behavior, Thought Problems, and Somatic Complaints scales of the TRF than did boys without chronic tic disorder (ADHD/-tics). Although many of the individual items that differentiated (p < .05) the two groups of boys pertained to behaviors that characterize motor tics, obsessions, or compulsions, the ADHD/+tics group exhibited higher rates of anxious behavior (CBCL) and obscene language (TRF) than did the ADHD/-tics group. Anxiety/depressive symptoms were associated with aggressive/oppositional behavior in both samples. Children with mild tic disorder were more similar (CBCL) to ADHD/-tics boys than they were to children with more severe tic disorder. The relatively higher rate of comorbidity in the ADHD/+tics group suggests that tics may be a marker for more severe symptomatology in clinic-referred samples of children with ADHD. Furthermore, these data suggest that it is not the presence, per se, but rather the severity of tic disorder that is associated with higher rates of emotional and behavioral disturbances.

Anxiety Disorders↗
PubMed1994

Telomere reduction of specific chromosome translocation in acute myelocytic leukemia.

The length of telomere restriction fragments (TRF) was studied by Southern blotting in 42 patients with acute myelocytic leukemia (AML) including 15 patients with 8;21 translocation, 8 with 15;17 translocation and 19 with a normal karyotype. The TRF length of leukemic cells with a normal karyotype and with 8;21 or 15;17 translocation showed significant reduction compared to that of lymphocytes from normal individuals (P < 0.05). In addition, there was a statistically significant difference in TRF length between leukemic cells with a normal karyotype and 8;21 translocation (P < 0.05). Therefore, the significant difference of telomere reduction in 8;21 translocation may be an important factor in the leukemogenic process.

Adolescent↗
PubMed2005

Psychiatric symptoms of children and adolescents with juvenile neuronal ceroid lipofuscinosis.

BACKGROUND: Juvenile neuronal ceroid lipofuscinosis (JNCL) is one of the most common neurodegenerative disorders in childhood and adolescence. The clinical picture includes diverse and complex psychiatric symptoms that are difficult to treat. Only symptomatic treatment is available. To improve symptomatic therapy, it is important to recognize the symptoms. The purpose of this study was to identify predominant psychiatric symptoms in patients with JNCL. METHODS: The study included 27 patients with JNCL with and without psychotropic treatment. The mean age was 15.2 (range 9-21) years. Characteristic psychiatric symptoms in this patient group were clarified by using the following standardized questionnaires filled in by parents, teachers and the patients themselves: Child Behavior Checklist (CBCL), Teacher Report Form (TRF) and Children's Depression Inventory (CDI). The symptoms were recorded for the entire study group and compared between patients with and without psychotropic treatment and between genders. RESULTS: The patients had a large number of psychiatric symptoms according to the CBCL and TRF. The most commonly reported symptoms were social, thought, attention problems, somatic complaints and aggressive behaviour. Patients receiving psychotropic medication had more psychiatric symptoms according to the CBCL and TRF. Moreover, female patients had more problems than male patients according to the CBCL. The total psychiatric symptom score was at clinical or borderline range for psychiatric disturbance in 74% of patients. The number of depressive symptoms reported by the patients themselves was low. CONCLUSIONS: JNCL patients suffer from a multitude of psychiatric symptoms. To improve drug choice and dosage, a thorough evaluation of these symptoms by standardized methods is needed before initiating treatment. Progress and possible adverse effects of treatment should be monitored on a regular basis.

Adolescent↗
PubMed2005

Telomere shortening occurs in Asian Indian Type 2 diabetic patients.

AIM: Telomere shortening has been reported in several diseases including atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection for Type 2 diabetes and premature coronary artery disease. The aim of this study was to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic patients. METHODS: Using Southern-blot analysis we determined mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leucocyte DNA. Type 2 diabetic patients without any diabetes-related complications (n = 40) and age- and sex-matched control non-diabetic subjects (n = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence method. RESULTS: Mean (+/- SE) TRF lengths of the Type 2 diabetic patients (6.01 +/- 0.2 kb) were significantly shorter than those of the control subjects (9.11 +/- 0.6 kb) (P = 0.0001). Among the biochemical parameters, only levels of TBARS showed a negative correlation with shortened telomeres in the diabetic subjects (r = -0.36; P = 0.02). However, telomere lengths were negatively correlated with insulin resistance (HOMA-IR) (r = -0.4; P = 0.01) and age (r = -0.3; P = 0.058) and positively correlated with HDL levels (r = 0.4; P = 0.01) in the control subjects. Multiple linear regression (MLR) analysis revealed diabetes to be significantly (P < 0.0001) associated with shortening of TRF lengths. CONCLUSIONS: Telomere shortening occurs in Asian Indian Type 2 diabetic patients.

Aging↗
PubMed1985

Mental health in Dutch children: (II). The prevalence of psychiatric disorder and relationship between measures.

This study concerns the second, more clinically oriented, part of our epidemiological project. The prevalence of child psychiatric disorders in random samples of 8- and 11-year-old children is assessed by using standardized parent- and child-interviews. The relationships between different measures of child psychopathology are determined. Furthermore, additional validity measures of the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) developed by Achenbach, are provided. Of the 153 8- and 11-year-old children selected through a two-stage sampling procedure, 116 (76%) children and their parents were intensively clinically assessed. The correlation between CBCL and direct child assessment is .42, whereas the correlation between the TRF and direct child assessment is .28. The correlation between TRF and CBCL is .26. The implications of the low correlation between raters who saw children is different situations are emphasized. The weight given to reports from different sources varies with the kind of problem the child exhibits. It is concluded that more research is needed to investigate the relative value of different types of data for different conditions. Seven percent of the 8- and 11-year-olds were judged severely disordered, whereas for 26% the clinicians judged the child to be moderately or severely disordered. The high prevalence rates found in our study compared with others is partly attributed to the arbitrary nature of clinical judgement. ANOVAs and discriminant function analysis were performed to obtain those CBCL items that showed the best discrimination between children who were clinically judged disordered and children from the normative comparison group. Many items found to be good discriminators of clinical status in this study were among the best discriminators of referral status in the earlier reported part of the study. A number of family and social factors were found to be associated with psychiatric disorder. These findings support those in other studies.

Adaptation, Psychological↗
PubMed1986

Mental health in Dutch children: (III). Behavioral-emotional problems reported by teachers of children aged 4-12.

Standardized teacher reports on children's behavioral-emotional problems can provide information on areas of children's functioning not readily accessible to other informants such as parents or clinicians. Once we accept the generally low agreement between different informants as inevitable, we may make use of the different types of information available from different sources. To do so we need base-line data from different informants that take account of key demographic variables such as gender, age and socio-economic status. In a previous report we provided such data for parent reported behavioral-emotional problems in children aged 4 through 16. In the present study we reported on the prevalence of a wide range of specific behavioral-emotional problems reported by teachers in a representative sample of 1,162 Dutch children aged 4 through 12; identified differences related to demographic variables and compared our data with those from other population based surveys. We used the Achenbach Teacher's Report Form (TRF) to collect our data because a comparison between different standardized teacher assessment instruments showed the TRF to be the most promising due to its solid psychometric background and its ready applicability. Our data supported the TRF's reliability and validity. For each of the 118 behavioral-emotional problems, the prevalence rates were presented graphically for both genders in two-year age groups. ANCOVAs were performed to assess the main effects and interaction of age and gender with SES as covariate for each problem item and total problem score. Of the demographic variables gender showed most numerous effects on problem items and showed the largest effect on total problem score. The main findings were: Boys obtained higher scores than girls. Many items on which boys scored higher are related to socially disapproved behavior. Boys obtained higher scores on concentration, attention and hyperactivity problems. Boys (especially the younger ones) scored higher on problems related to academic functioning. Teacher reports revealed larger gender differences than parent reports. Both parents and teachers scored boys higher on items predominantly associated with the externalizing syndrome. More boys than girls were attending education in special schools. Age showed no significant effect on total problem score, although older children were scored higher on a number of items associated with academic, somatic and social functioning and with emotions related to inner feelings.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1996

Telomere length in human liver diseases.

To determine the role of telomere-mediated gene stability in hepatocarcinogenesis, we examined the telomere length of human liver with or without chronic liver diseases and hepatocellular carcinomas (HCC). The mean telomere restriction fragment (TRF) length of normal liver (n = 13), chronic hepatitis (n = 11), liver cirrhosis (n = 24) and HCC (n = 24) was 7.8 +/- 0.2, 7.1 +/- 0.3, 6.4 +/- 0.2 and 5.2 +/- 0.2 kb, respectively (mean +/- standard error). TRF length decreased with a progression of chronic liver diseases and that in HCC was significantly shorter than that in other chronic liver diseases (p < 0.05). The ratios of TRF length of HCC to that of corresponding surrounding liver of well differentiated (n = 7), moderately differentiated (n = 10) and poorly differentiated (n = 4) HCCs were 0.83 +/- 0.06, 0.75 +/- 0.05 and 0.98 +/- 0.09, respectively. The ratio of poorly differentiated HCC was significantly higher than that of moderately differentiated HCC (p < 0.05). A comparison between the size and telomere length ratio of moderately differentiated HCCs revealed a decrease of the ratio with size until it reached 50 mm in diameter. In contrast, the ratio increased as the size enlarged over 50 mm. These findings suggest that the gene stability of the liver cells mediated by the telomere is reduced as chronic liver disease progresses and that telomerase is activated in poorly differentiated HCC and moderately differentiated HCC over 50 mm in diameter.

Adolescent↗
PubMed1999

Telomere dynamics in monkeys: increased cell turnover in macaques infected with chimeric simian-human immunodeficiency viruses.

To address the question of how cell turnover is affected by retroviral infections, we used the telomeric terminal restriction fragments (TRFs) as markers of cell replicative history and measured their length in macaques infected with chimeric simian-human immunodeficiency viruses (SHIVs). The TRF lengths of mononuclear cells in 104 samples, including longitudinal samples from nine cynomolgus and ten pig-tailed macaques infected with SHIV, and in samples from 26 uninfected macaques, were quantitated by an improved method, based on two-dimensional calibration of DNA sizes, pulsed field electrophoresis, and high-resolution Southern blot images. The average TRF lengths of peripheral blood mononuclear cells (PBMCs) from uninfected pig-tailed (14.9+/-1.6 kbp) and cynomolgus (14.1+/-1.8 kbp) macaques were about 3 and 5 kbp longer than those of human infants and 30-year-old adults, respectively. The rate of TRF length shortening in infected pig-tailed macaques was significantly (P = 0.035) higher (2.2-fold) than in uninfected monkeys. The TRFs in SHIV-infected cynomolgus monkeys, which, in general, had lower viral loads than pig-tailed macaques, shortened on average more rapidly (1.6-fold) than in uninfected animals, but the difference was not statistically significant. The TRFs of mononuclear cells from the lymph nodes of two rapidly progressing SHIV-infected macaques that developed AIDS and died also shortened in parallel but somewhat more rapidly than in the PBMCs. These results suggest that the rate of PBMC turnover in macaques could be increased several-fold during infections by immunodeficiency viruses, likely due to immune activation by SHIV antigens.

Animals↗
PubMed1995

A human telomeric protein.

Telomeres are multifunctional elements that shield chromosome ends from degradation and end-to-end fusions, prevent activation of DNA damage checkpoints, and modulate the maintenance of telomeric DNA by telomerase. A major protein component of human telomeres has been identified and cloned. This factor, TRF, contains one Myb-type DNA-binding repeat and an amino-terminal acidic domain. Immunofluorescent labeling shows that TRF specifically colocalizes with telomeric DNA in human interphase cells and is located at chromosome ends during metaphase. The presence of TRF along the telomeric TTAGGG repeat array demonstrates that human telomeres form a specialized nucleoprotein complex.

Amino Acid Sequence↗
PubMed1996

T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover.

Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that CD8(+) T cell TRF length decreased but CD4(+) T cell TRF length was stable during the course of human immunodeficiency virus type-1 (HIV-1) infection, which was not explained by differential telomerase activity. This observation provides evidence that turnover in the course of HIV-1 infection can be increased considerably in CD8(+) T cells, but not in CD4(+) T cells. These results are compatible with CD4(+) T cell decline in HIV-1 infection caused by interference with cell renewal.

Acquired Immunodeficiency Syndrome↗