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J Roberts

Publications and source records attributed to J Roberts.

At least 73 records · Page 4Linked to original sources
PubMed2000

Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events.

The c-myc gene has been implicated in three distinct genetic programs regulating cell proliferation: control of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth. We have now used p27(-/-) fibroblasts to dissect these downstream signalling pathways. In these cells, activation of Myc stimulates transcription of E2F target genes, S-phase entry and cell growth without affecting cyclin E-cdk2 kinase activity. Both cyclin D2 and E2F2, potential direct target genes of Myc, are induced in p27(-/-) MycER cells. Ectopic expression of E2F2, but not of cyclin D2, induces S-phase entry, but, in contrast to Myc, does not stimulate cell growth. Our results show that stimulation of cyclin E-cdk2 kinase, of E2F-dependent transcription and of cell growth by Myc can be genetically separated from each other.

3T3 Cells↗
PubMed2000

T-cell lymphoproliferative disorder in an aged rhesus macaque.

A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although leukemia and lymphoma in nonhuman primates are commonly associated with simian T-lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types C, D, and E retroviruses, this monkey was not infected with any of these viruses. However, the monkey did have antibodies against herpesvirus saimiri. This likely represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that were identified as having antibodies against herpesvirus saimiri. Rhesus rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to lymphoproliferative disorders in primates and humans, respectively. Moreover, an oncogene has been recently identified in the RRV genome that is equivalent in position to the herpesvirus saimiri and KSHV oncogenes. Presently, the association of RRV infection with disease in nonhuman primates is unknown.

Age Factors↗
PubMed2000

Decreased nuclear factor-kappaB DNA binding activity following permanent focal cerebral ischaemia in the rat.

Many factors implicated in the pathogenesis of cerebral ischaemia such as glutamate, tumour necrosis factor and interleukin-1 have also been shown to activate nuclear factor-kappaB (NF-kappaB). In the present study we have investigated NF-kappaB activity at various times following permanent focal cerebral ischaemia in rats using immunohistochemistry, western blotting and electrophoretic mobility shift assay (EMSA). Three hours following middle cerebral artery occlusion nuclear translocation of NF-kappaB was detected using immunohistochemical and western blotting techniques. This was reflected in a trend towards increased NF-kappaB binding activity (EMSA) in the ischaemic cortex compared to histologically normal tissue. In contrast however, from 6 to 48 h post-occlusion nuclear translocation and NF-kappaB binding activity was decreased in the ischaemic cortex. Decreased NF-kappaB binding activity detected in degenerating neurones, suggests that decreased NF-kappaB activity may exacerbate ischaemia induced neuronal cell death.

Animals↗
PubMed2000

Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.

Cat's claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat's claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat's claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat's claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat's claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis.

Animals↗
PubMed2000

Extractionless determination of 6-methoxy-2-naphthylacetic acid, a major metabolite of nabumetone, in human plasma by high-performance liquid chromatography.

Following oral administration of the prodrug nabumetone, the major metabolite 6-methoxy-2-naphthylacetic acid (6-MNA) was determined in human plasma. Minimal sample preparation was followed by reversed-phase liquid chromatography and UV detection, affording high sample throughput. The lower limit of quantification (LLOQ) was 70 ng/ml, at a signal-to-noise ratio of 8:1. The assay method displayed good correlation (r=0.997), and can be readily employed in pharmacokinetic and bioequivalence studies.

Adult↗
PubMed2000

Risks of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes mellitus. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVES: This study was undertaken to determine the frequencies of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes. STUDY DESIGN: This was a prospective observation of pregnancy outcomes among 462 women with pregestational diabetes mellitus (White classes B-F) and singleton pregnancies who were enrolled in a multicenter trial to compare low-dose aspirin with placebo for preeclampsia prevention. The main outcome measures were preeclampsia and neonatal outcomes. RESULTS: Among 462 women with pregestational diabetes, 92 (20%) had preeclampsia. Preeclampsia frequency rose significantly with increasing severity of diabetes according to White classification (class B, 11%; class C, 22%; class D, 21%; class R plus class F, 36%; P <.0001). Preeclampsia was also more common among women who had proteinuria at baseline (28% vs 18%; odds ratio, 1.75; 95% confidence interval, 1.02-3.01). Frequency of preterm delivery at <35 weeks' gestation rose greatly with increasing severity of diabetes (P =.0002). Women with proteinuria at baseline were significantly more likely to be delivered at <35 weeks' gestation (29% vs 13%; odds ratio, 2.6; 95% confidence interval, 1.5-4.6) and to have small-for-gestational-age infants (14% vs 3%; odds ratio, 5. 4; 95% confidence interval, 2.7-17.7), and they were less likely to have large-for-gestational-age infants (14% vs 40%; odds ratio, 0.2; 95% confidence interval, 0.1-0.5). CONCLUSION: Among women with pregestational diabetes mellitus, the frequency of preeclampsia rose with increasing severity of diabetes. Proteinuria early in pregnancy was associated with marked increases in adverse neonatal outcomes independent of preeclampsia development.

Aspirin↗
PubMed2000

Hypertensive disorders in twin versus singleton gestations. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: This study was undertaken to compare rates and severity of gestational hypertension and preeclampsia, as well as perinatal outcomes when these complications develop, between women with twin gestations and those with singleton gestations. STUDY DESIGN: This was a secondary analysis of prospective data from women with twin (n = 684) and singleton (n = 2946) gestations enrolled in two separate multicenter trials of low-dose aspirin for prevention of preeclampsia. End points were rates of gestational hypertension, rates of preeclampsia, and perinatal outcomes among women with hypertensive disorders. RESULTS: Women with twin gestations had higher rates of gestational hypertension (relative risk, 2.04; 95% confidence interval, 1.60-2.59) and preeclampsia (relative risk, 2. 62; 95% confidence interval, 2.03-3.38). In addition, women with gestational hypertension during twin gestations had higher rates of preterm delivery at both <37 weeks' gestation (51.1% vs 5.9%; P <. 0001) and <35 weeks' gestation (18.2% vs 1.6%; P <.0001) and also had higher rates of small-for-gestational-age infants (14.8% vs 7. 0%; P =.04). Moreover, when outcomes associated with preeclampsia were compared, women with twin gestations had significantly higher rates of preterm delivery at <37 weeks' gestation (66.7% vs 19.6%; P <.0001), preterm delivery at <35 weeks' gestation (34.5% vs 6.3%; P <.0001), and abruptio placentae (4.7% vs 0.7%; P =.07). In contrast, among women with twin pregnancies, those who remained normotensive had more adverse neonatal outcomes than did those in whom hypertensive complications developed. CONCLUSIONS: Rates for both gestational hypertension and preeclampsia are significantly higher among women with twin gestations than among those with singleton gestations. Moreover, women with twin pregnancies and hypertensive complications have higher rates of adverse neonatal outcomes than do those with singleton pregnancies.

Abruptio Placentae↗
PubMed2000

Evidence of a T(H) 1 type response associated with recurrent miscarriage.

OBJECTIVE: To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic setting. PATIENT(S): Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Serum levels of IL-10 and IFN-gamma. RESULT(S): Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. CONCLUSION(S): These results support the view that miscarriage is associated with a T(H) 1 type response.

Abortion, Habitual↗
PubMed2000

Classical anomia: a neuropsychological perspective on speech production.

We present data collected from two anomic aphasics. Thorough assessment of comprehension, oral reading and repetition revealed no underlying impairments suggesting that both patients were examples of classical anomia--word-finding difficulties without impaired semantics or phonology. We describe a series of experiments in which the degree of anomia was both increased and decreased, by cueing or priming with either a semantically related word or the target item. One of the patients also presented with an 'acquired' tip-of-the-tongue phenomenon. He was able to indicate with a high-degree of accuracy the syllable length of the target, and whether or not it was a compound word. Neither patient could provide the first sound/letter. The data are discussed in terms of discrete two-stage models of speech production, an interactive-activation theory and a distributed model in which the positive and negative computational consequences of the arbitrary relationship between sound and meaning are emphasised.

Adult↗
PubMed2000

TR3 death receptor expression in the normal and ischaemic brain.

Members of the death receptor family may play a prominent role in developmental and pathological neuronal cell death. We report the expression of the TR3 and TR7 death receptors in the adult human and rat central nervous system. Whereas expression of TR3 appears to be high in the human cerebellum, with lower levels in other brain regions, robust expression is observed in many regions of the rat brain. We also analyzed modulation of death receptor expression in an in vivo rat model of acute stroke. In contrast to tumor necrosis factor receptor 1, Fas and p75(NGFR), which all show up-regulation specifically in lesioned cortex of the permanent middle cerebral artery occlusion model of stroke. TR3 shows a rapid global increase in both lesioned and unlesioned brain. In comparison, the recently described death receptor TR7 shows no change in this model. These data indicate that the death receptors show clear differences in patterns of expression in response to ischemic injury. ¿ 2000 IBRO. Published by Elsevier Science Ltd.

Amino Acid Sequence↗
PubMed2000

Recurrent detoxification may elevate alcohol craving as measured by the Obsessive Compulsive Drinking scale.

Research has demonstrated a relationship between the number of previous alcohol detoxifications and increased severity of the alcohol withdrawal syndrome (AWS) that is hypothesized to be similar to an electrophysiologic "kindling process." Application of a "kindling" model to AWS suggests that neuroadaptation of the central nervous system to repeated detoxifications may also cause neurobehavioral alterations that may affect "craving." This study examined craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS) in 67 adult outpatients meeting DSM-IV criteria (American Psychiatric Association, 1994) for alcohol dependence and AWS having either < 2 and > or = 2 previous detoxifications. Results of ANCOVA revealed that patients with > or = 2 previous detoxifications had higher scores on a scale that measures obsessive thoughts about alcohol, drinking urges and behaviors, and a composite of these scores after controlling for alcohol dependence severity, depressive symptoms and number of drinks 2 weeks prior to the study. Findings emphasize the need to address craving and other psychological variables with respect to treatment of AWS.

Adult↗
PubMed2000

Health care service use and sexual communication: past experience and future intention of high-risk male adolescents.

High-risk male adolescents were surveyed to collect data to be used to develop strategies to enhance communication with their partners about sexually transmitted diseases (STDs). Participants were concerned about acquiring an STD from their partner, and reported an increased likelihood of communicating about STD-related issues when confidential health care was available.

Adolescent↗
PubMed2000

Late-talking toddlers: MLU and IPSyn outcomes at 3;0 and 4;0.

Expressive language outcomes measured by MLU and the Index of Productive Syntax (IPSyn) at ages 3;0 and 4;0 were investigated in 34 late talkers with normal receptive language identified between 2;0 to 2;7 and 16 typically developing comparison children matched on age, SES, and nonverbal ability. Late talkers made greater gains than comparison children between 3;0 and 4;0 in both MLU and IPSyn raw score. However, when age-standardized z-scores were analysed, the late talkers were about 2.5 standard deviations below comparison children on both measures at both ages. At 3;0, 41% of the late talkers had MLUs above the 10th percentile based on Scarborough's (1990) benchmark sample; by 4;0, 71% did so. Using the IPSyn, a more stringent measure, 34% scored above the 10th percentile at 3;0 and only 29% did so at 4;0. MLU was significantly correlated with the IPSyn at both ages for the late talkers, but only at 3;0 for the comparison children. A converging set of regression analyses indicated no group differences in the predictive relationship between MLU and IPSyn, suggesting that the late talkers were delayed on both measures but not deviant in their development.

Child Language↗
PubMed2000

Finasteride increases anagen hair in men with androgenetic alopecia.

BACKGROUND: The growth of scalp hair is a cyclical process of successive phases of growth (anagen) and rest (telogen). In previous clinical trials in men with androgenetic alopecia, treatment with finasteride increased scalp hair counts in a defined area (i.e. increased hair density). OBJECTIVES: The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle. PATIENTS/METHODS: Two hundred and twelve men, age 18-40 years, with androgenetic alopecia were randomized to receive finasteride 1 mg daily or placebo for 48 weeks. At baseline and at 24 and 48 weeks, macrophotographs were taken to measure total and anagen hair count in a 1-cm(2) target area of the scalp. RESULTS: At baseline, mean total and anagen hair counts in the finasteride group were 200 and 124 hairs, respectively (% anagen = 62%) and the anagen to telogen ratio was 1.74 (geometric mean). In the placebo group, the respective values were 196 and 119 hairs (% anagen = 60%) and 1.57. At week 48, the finasteride group had a net improvement (mean +/- SE) compared with placebo in total and anagen hair counts of 17.3 +/- 2.5 hairs (8.3% +/- 1.4%) and 27.0 +/- 2.9 hairs (26% +/- 3.1%), respectively (P < 0.001). Furthermore, treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47% (P < 0.001). In this study, treatment with finasteride 1 mg day(-1) for 48 weeks increased both total and anagen hair counts, and improved the anagen to telogen ratio. CONCLUSIONS: These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients.

Adolescent↗
PubMed2000

Development of a health-related quality of life questionnaire for women with androgenetic alopecia.

Despite the negative effects of androgenetic alopecia (AGA), no standardized health-related quality of life (HRQOL) questionnaire which is both specific to women and suitable for use in clinical trials currently exists. A questionnaire to assess HRQOL in women with AGA, the Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QOL), was recently developed. Aspects of life affected by AGA were generated from literature review, discussion with experts, and a focus group. The number of issues identified was reduced based on importance and relevance to women with AGA. A questionnaire was then constructed and pilot-tested for comprehension. The resulting 25-item instrument was later included in a double-blind, placebo-controlled clinical trial of finasteride 1 mg for the treatment of hair thinning in postmenopausal women (n = 137). Based on test characteristics, several questions were eliminated, resulting in a 16-item questionnaire. The WAA-QOL exhibited excellent test-retest reliability overall (intraclass correlation coefficient = 0.89), and for individual items (kappa = 0.66-0.85), as well as high internal consistency (Crohnbach's alpha = 0.98). Responsiveness of the questionnaire could not be assessed. The WAA-QOL is self-completed in about 10 min, exhibits good content validity, internal consistency, and test-retest reliability, and may be useful in assessing the impact of female AGA on HRQOL or in evaluating therapeutic effects in clinical trials.

Adult↗
PubMed2000

The Preterm Prediction Study: association of second-trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth.

OBJECTIVE: This study was undertaken to determine the association between genitourinary tract infection with Chlamydia trachomatis and spontaneous preterm birth. STUDY DESIGN: Genitourinary tract infection with C trachomatis was determined with a ligase chain reaction assay of voided urine samples collected at 24 weeks' gestation (22 weeks' to 24 weeks 6 days' gestation) and 28 weeks' gestation (27 weeks' to 28 weeks 6 days' gestation). Case patients (spontaneous preterm birth at <37 weeks' gestation; n = 190) and control subjects (delivery at >/=37 weeks' gestation, matched for race, parity, and center; n = 190) were selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. RESULTS: Genitourinary C trachomatis infection (11% overall) was significantly more common among the case patients than among the control subjects at 24 weeks' gestation (15.8% vs 6.3%; P =.003) but not at 28 weeks' gestation (12.6% vs 10.9%; P =.61). Women with chlamydia infection were more likely to have bacterial vaginosis (57.1% vs 32.9%; P =.002) and a short cervical length (</=25 mm; 33.0% vs 17.9%; P =.02) but not a body mass index <19.8 kg/m(2) (35.0% vs 23.9%; P =.17) or a positive fetal fibronectin test result (7.1% vs 9.5%; P =.62). After adjustment for risk factors for spontaneous preterm birth, women with C trachomatis infection at 24 weeks' gestation were 2 times as likely as uninfected women to have a spontaneous preterm birth at <37 weeks' gestation (odds ratio, 2.2; 95% confidence interval, 1.03-4.78) and 3 times as likely to have a spontaneous preterm birth at <35 weeks' gestation (odds ratio, 3.2; 95% confidence interval, 1.08-9.57). CONCLUSION: Genitourinary C trachomatis infection at 24 weeks' gestation was associated with a 2-fold to 3-fold increased risk of subsequent spontaneous preterm birth.

Adolescent↗