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Biomedical subjects

J M Roberts

Publications and source records attributed to J M Roberts.

At least 91 records · Page 5Linked to original sources
PubMed1999

High-resolution ultrasound to diagnose melanoma metastases in patients with clinically palpable lymph nodes.

High-resolution ultrasound was used to determine if it could predict the presence of metastatic disease in 52 patients with melanoma who had developed newly palpable lymph nodes during clinical follow-up. Ultrasound proved accurate in diagnosing the presence of nodal metastases; it had a sensitivity of 94%, a specificity of 87% and an accuracy of 89%. The ultrasound features which together were diagnostic of the presence of nodal metastases were a node thickness greater than two-thirds of the node length and the presence of low-level echoes in the node. When these two features were both present on ultrasound, node metastases were present in every case. Ultrasound can be used to evaluate newly palpable lymph nodes in patients with melanoma. A normal ultrasound finding does not exclude micrometastases, but a lymph node showing the two key ultrasound features aforementioned is highly likely to contain metastatic disease and should be treated accordingly.

Diagnosis, Differential↗
PubMed1999

Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy.

Nitric oxide (NO) synthase (NOS) is active in the gravid uterus, and its activity decreases prior to the onset of parturition. We tested the hypothesis that NO helps maintain uterine quiescence by suppressing the expression of genes necessary for parturition. Pregnant rats (18 days gestation) were treated with inducible NOS (iNOS) inhibitor N-iminoethyl-L-lysine (NIL) or endothelial NOS inhibitor nitro-L-arginine methyl ester (L-NAME); 24 h later, uteri were analyzed for myometrial connexin 43 (Cx43) protein by immunoblotting and mRNA by Northern analysis. Myometrial oxytocin receptors (OTR) were measured by radioligand binding, and decidual prostaglandin H synthase (PGHS) protein by immunoblotting. Uterine NOS blockade was verified by NOS activity assay. We found that NIL, but not L-NAME, significantly increased myometrial Cx43 protein to parturitional levels with treatment at 19 but not 17 days gestation. Steady state mRNA concentrations were not changed at 24 h. NOS inhibition did not increase the concentrations of OTR, or PGHS protein, nor did it decrease maternal serum progesterone. We conclude that endogenous uterine NO from iNOS suppresses myometrial Cx43 gap junction protein expression during rat pregnancy. Although the exact mechanism is unknown, an increase of uterine wall stretch due to inhibition of relaxation could account for increased Cx43 gene transcription.

Animals↗
PubMed1999

Detection by enzyme immunoassay of serum immunoglobulin G antibodies that recognize specific Cryptosporidium parvum antigens.

Human infection with Cryptosporidium parvum usually elicits characteristic immunoglobulin G (IgG), IgA, and IgM antibody responses against two sporozoite surface antigens with apparent molecular masses of approximately 27 and 17 kDa. We have determined that these two antigens are actually complex families of related antigens. We have developed two new enzyme-linked immunosorbent assays (ELISAs) for the detection and quantitation of serum IgG antibodies against both antigens. The assays utilize a recombinant form of the 27-kDa antigen and a partially purified native fraction isolated from sonicated whole oocysts that contains 17-kDa antigen. An immunoblot assay previously developed in our laboratory served as the reference, or "gold standard," seroassay for the assessment of the new ELISAs. Positive responses with the recombinant-27-kDa-antigen ELISA were correlated with the immunoblot results for the 27-kDa antigen, with a sensitivity and specificity of 90 and 92%, respectively. Similarly, positive responses with the partially purified native-17-kDa-antigen ELISA correlated with the immunoblot results for the 17-kDa antigen, with a sensitivity and specificity of 90 and 94%, respectively. For both ELISAs the median IgG antibody levels for serum sets collected during outbreaks of waterborne C. parvum infection were at least 2.5-fold higher than the levels determined for a nonoutbreak set. Using the immunoblot as the "gold standard," the new ELISAs were more specific and, in the case of the 27-kDa-antigen ELISA, more sensitive than the crude oocyst antigen ELISA currently in use. These assays will be useful in future epidemiologic studies.

Animals↗
PubMed1999

Effect of stretching duration on active and passive range of motion in the lower extremity.

OBJECTIVES: To investigate the effect of different durations of stretching (five or 15 seconds) on active and passive range of motion (ROM) in the lower extremity during a five week flexibility training programme. METHOD: Twenty four university sport club members (19 men, five women), with a mean (SD) age of 20.5 (1.35) years, were randomly assigned to one of three groups (two treatment and one control). The two treatment groups participated in a static active stretching programme three times a week for a five week period, holding each stretch for a duration of either five or 15 seconds. The total amount of time spent in a stretched position was controlled. The five second group performed each stretch nine times and the 15 second group three times resulting in a total stretching time of 45 seconds for both groups for each exercise. The control group did not stretch. Active and passive ROM were determined during left hip flexion, left knee flexion, and left knee extension before and after the training programme using an inclinometer. RESULTS: Two factor within subject analysis of variance indicated no significant difference in ROM before and after the training programme for the control group. However, significant improvements in active and passive ROM (p < 0.05) were shown in both treatment groups after the five week training programme. Two factor analysis of variance with repeated measures and post hoc analysis showed significant differences between the treatment groups and the control group for the improvements observed in active (p < 0.05) and passive (p < 0.05) ROM. The five and 15 second treatment groups did not differ from one another when ROM was assessed passively, but significant differences were apparent for active ROM, with the 15 second group showing significantly greater improvements (p < 0.05) than the five second group. CONCLUSION: These findings suggest that holding stretches for 15 seconds, as opposed to five seconds, may result in greater improvements in active ROM. However, sustaining a stretch may not significantly affect the improvements gained in passive ROM.

Adult↗
PubMed1999

Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1).

Proliferation and apoptosis are increased in many types of inflammatory diseases. A role for the cyclin kinase inhibitor p27(Kip1) (p27) in limiting proliferation has been shown. In this study, we show that p27(-/-) mesangial cells and fibroblasts have strikingly elevated rates of apoptosis, not proliferation, when deprived of growth factors. Apoptosis was rescued by restoration of p27 expression. Cyclin A-cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E-CDK2 activity, was increased in serum-starved p27(-/-) cells, and decreasing CDK2 activity, either pharmacologically (Roscovitine) or by a dominant-negative mutant, inhibited apoptosis. Our results show that a new biological function for the CDK inhibitor p27 is protection of cells from apoptosis by constraining CDK2 activity. These results suggest that CDK inhibitors are necessary for coordinating the cell cycle and cell-death programs so that cell viability is maintained during exit from the cell cycle.

Animals↗
PubMed1999

Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren.

This randomized, placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths (albendazole) and lymphatic filariasis (ivermectin). Children were infected with Ascaris (29.2%), Trichuris (42.2%), and hookworm (6.9%), with 54.7% of children having one or more of these parasites. Wuchereria bancrofti microfilaria were found in 13.3% of the children. Children were randomly assigned to treatment with placebo, albendazole, ivermectin, or combined therapy. Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone. Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone. Only combination therapy resulted in significantly greater gains in height (hookworm-infected children) or weight (Trichuris-infected children) compared with the placebo group. Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and resulted in nutritional benefits not found with either drug alone.

Albendazole↗
PubMed1999

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative. Parasite prevalence (all species) decreased with age (from a high of 83% among children 1-4 years old to 60% among children 10-14 years old). Even more dramatic decreases were noted in the prevalence of high density falciparum infection (from 37% among children 12-23 months old to < 1% among 10-14-year-old children) and in clinical malaria (20% to 0.3% in the same age groups). Children < 1 year of age accounted for 55% of all cases of anemia detected. Anemia was consistently associated with high density infection in children < 10 years of age (20% to 210% increased risk relative to aparasitemic children). These results demonstrate the relationship between high-density malaria infection and two clinical manifestations of malarial illness.

Adolescent↗
PubMed1998

The murine gene p27Kip1 is haplo-insufficient for tumour suppression.

p27Kip is a candidate human tumour-suppressor protein, because it is able to inhibit cyclin-dependent kinases and block cell proliferation. Abnormally low levels of the p27 protein are frequently found in human carcinomas, and these low levels correlate directly with both histological aggressiveness and patient mortality. However, it has not been possible to establish a causal link between p27 and tumour suppression, because only rare instances of homozygous inactivating mutations of the p27 gene have been found in human tumours. Thus, p27Kip1 does not fulfil Knudson's 'two-mutation' criterion for a tumour-suppressor gene. Here we show that both p27 nullizygous and p27 heterozygous mice are predisposed to tumours in multiple tissues when challenged with gamma-irradiation or a chemical carcinogen. Therefore p27 is a multiple-tissue tumour suppressor in mice. Molecular analyses of tumours in p27 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Hence, p27 is haplo-insufficient for tumour suppression. The assumption that null mutations in tumour-suppressor genes are recessive excludes those genes that exhibit haplo-insufficiency.

Animals↗
PubMed1998

p27Kip1 alters the response of cells to mitogen and is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation.

BACKGROUND: In many vertebrate cell lineages, precursor cells divide a limited number of times before they arrest and terminally differentiate into postmitotic cells. It is not known what causes them to stop dividing. We have been studying the 'stopping' mechanism in the proliferating precursor cells that give rise to oligodendrocytes, the cells that make myelin in the central nervous system. We showed previously that the cyclin-dependent kinase inhibitor p27Kip1 (p27) progressively accumulates in cultured precursor cells as they proliferate and that the time course of the increase is consistent with the possibility that p27 accumulation is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation at the appropriate time. RESULTS: We now provide direct evidence that p27 is part of the intrinsic timer. We show that although p27-/- precursor cells stop dividing and differentiate almost as fast as wild-type cells when deprived of mitogen, when stimulated by saturating amounts of mitogen they have a normal cell-cycle time but tend to go through one or two more divisions than wild-type cells before they stop and differentiate. Cells that are p27+/- behave in an intermediate way, going through at most one extra division, indicating that the levels of p27 matter in the way the timer works. We also show that p27-/- precursor cells are more sensitive than wild-type cells to the mitogenic effect of platelet-derived growth factor. CONCLUSIONS: These findings demonstrate that p27 is part of the normal timer that determines when oligodendrocyte precursor cells stop dividing and differentiate, at least in vitro. It seems likely that p27 plays a similar role in many other cell lineages, which could explain the phenotypes of the p27-/- and p27+/- mice.

Animals↗
PubMed1998

Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein.

Considerable advances have been made in characterizing the cyclins and cyclin-dependent kinases (CDKs) that are necessary for progression through the cell cycle, but there has been relatively lesser success in identifying the specific biochemical pathways and cell cycle events that are directly under CDK control. To identify physiologically significant CDK substrates we generated mutations in cyclin E that altered the ability of the cyclin to direct the cyclin-CDK holoenzyme to specific in vivo substrates. We show that one of these mutations defines a domain in cyclin E necessary for phosphorylation of the retinoblastoma protein (Rb). These observations confirm the idea that cyclins contribute to substrate recognition by cyclin-CDK complexes, demonstrate the utility of targeting mutants in the identification of essential cyclin-CDK substrates, and put cyclin E squarely into the family of proteins designed to regulate Rb.

3T3 Cells↗
PubMed1998

Plasma ferritin, premature rupture of membranes, and pregnancy outcome.

OBJECTIVE: The objective of this study was to determine whether plasma ferritin levels predict maternal or neonatal outcomes in women with preterm rupture of membranes at <32 weeks' gestation. METHODS: Plasma from 223 women with premature rupture of membranes at <32 weeks' gestation who had participated in a randomized antibiotic trial were analyzed for ferritin at random assignment and at delivery, and the results were compared with the development of clinical chorioamnionitis, latency until delivery, neonatal sepsis, and a composite adverse neonatal outcome variable. RESULTS: The mean plasma ferritin level rose from 19.2 +/- 29.1 microgram/L on admission to 38.3 +/- 54.3 microgram/L at delivery, with a mean latency of 9.3 +/- 14.6 days. Plasma ferritin levels were significantly higher at both times in mothers whose infants acquired sepsis than in those whose infants did not, especially at delivery (68.5 +/- 96.3 microgram/L vs 32.5 +/- 40.5 microgram/L, P =.01), and neonatal sepsis was 2 to 3 times more common among women with plasma ferritin levels above the median than among those with levels below the median. CONCLUSIONS: Among women with premature rupture of membranes at <32 weeks' gestation, plasma ferritin levels were significantly associated with neonatal sepsis. These data suggest that higher plasma ferritin levels may serve as a marker of infection among women with premature rupture of membranes; however, the clinical utility of plasma ferritin levels in predicting neonatal outcome appears limited.

Adult↗
PubMed1998

Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation.

OBJECTIVE: We tested the hypothesis that the independent risk factor for atherosclerosis of increased plasma homocysteine concentration is associated with the pregnancy syndrome of preeclampsia. We further hypothesized that increased plasma homocysteine concentration during pregnancy may advance endothelial dysfunction in preeclampsia by promoting oxidative stress. STUDY DESIGN: Antepartum blood samples were collected >/=6 hours after the last meal from 33 women with normal, uncomplicated pregnancies and from 21 women with preeclampsia. These plasma samples were analyzed for concentrations of total homocysteine; folate; triglycerides; creatinine; a marker of endothelial activation, cellular fibronectin; and a marker of oxidative stress, malondialdehyde. RESULTS: The mean value of total plasma homocysteine in preeclampsia was significantly higher than that observed in normal pregnancy (P <. 04). Similarly, plasma malondialdehyde (P <.001), triglyceride (P <. 001), and cellular fibronectin (P <.006) concentrations were also greater in women with preeclampsia than in control subjects. However, no differences were observed between women with preeclampsia and control subjects in folate (P =.97) or creatinine (P =.28) concentrations. Homocysteine concentration did not correlate with plasma creatinine (P =.61), malondialdehyde (P =.32), or triglyceride (P =.89) concentrations. However, cellular fibronectin concentration correlated positively with homocysteine concentration in both women with preeclampsia and control subjects (r = 0.87, P <. 0001, and r = 0.50, P <.004, respectively), and folate concentrations were weakly but negatively correlated with homocysteine values (P =.03, r = 0.32). CONCLUSIONS: Total plasma homocysteine concentration is increased in preeclampsia and is significantly correlated with cellular fibronectin concentration, suggesting that homocysteine plays a role in promoting endothelial dysfunction in preeclampsia. Furthermore, despite the use of pregnancy multivitamins and no indications of overt folate deficiency in this subject population, homocysteine concentration weakly and negatively correlates with plasma folate concentration.

Adult↗
PubMed1998

Maternal serum thromboxane B2 concentrations do not predict improved outcomes in high-risk pregnancies in a low-dose aspirin trial. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medical Units.

OBJECTIVE: The aim of the study was too determine whether, in a low-dose aspirin trial in high-risk pregnancies, a decrease in maternal serum thromboxane B2 level predicted improved pregnancy outcomes. STUDY DESIGN: This multicenter, randomized, double-blind trial included 2539 women, 1010 of whom had sufficient serum samples at enrollment and at 24 to 28 weeks' gestation, 34 to 38 weeks' gestation, or both to assess longitudinal changes in thromboxane B2 level and their effects on pregnancy outcomes. Women were randomly assigned between 13 and 26 weeks' gestation to receive daily aspirin (60 mg) or placebo. RESULTS: Overall and in all subgroups women assigned to receive aspirin had markedly lower maternal thromboxane B2 concentration values than did those assigned to receive a placebo (P =.0001). Changes in thromboxane levels were not, however, correlated with adverse pregnancy outcomes. Women with >/=50% reduction in maternal serum thromboxane B2 concentrations from baseline had occurrences of preeclampsia (P =.922), preterm birth (P =.375), small for gestational age neonates (P =.938), and grade III or IV intraventricular hemorrhage (P = 1.000) similar to those of women who had <50% reduction. Similar results were found for women with thromboxane B2 level decreases of <15 versus >15 ng/mL and women with thromboxane B2 level decreases to <10 versus >/=10, <5 versus >/=5, and <1 versus >/=1 ng/mL. Maternal thromboxane B2 concentrations at enrollment were also not predictive of adverse outcomes. CONCLUSION: Neither maternal serum thromboxane B2 concentrations at enrollment nor their subsequent reduction were predictive of adverse pregnancy outcomes in a low-dose aspirin trial.

Aspirin↗
PubMed1998

The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development.

OBJECTIVE: Preterm births occur for many different reasons. Most efforts to identify risk factors for preterm births either ignore cause and consider preterm births as a single entity or examine risk factors for spontaneous preterm births. We performed this study to examine risk factors for indicated preterm births, which constitute more than one quarter of all preterm births. STUDY DESIGN: The study included 2929 women evaluated at 24 weeks' gestation at 10 centers. Information was gathered about demographic factors, socioeconomic status, home and work environments, drug and alcohol use, and medical history. In addition vaginal samples were evaluated for fetal fibronectin and bacterial vaginosis and cervical length was measured by transvaginal ultrasonography. Associations with indicated preterm birth were evaluated by univariate tests and by multivariable analysis with logistic regression. RESULTS: Of the women studied at 24 weeks' gestation 15.3% were delivered of their infants at <37 weeks' gestation. Of these deliveries, 27.7% were indicated preterm births. Risk factors in the final multivariable model were, in order of decreasing odds ratios, mullerian duct abnormality (odds ratio 7.02), proteinuria at <24 weeks' gestation (odds ratio 5.85), history of chronic hypertension (odds ratio 4.06), history of previous indicated preterm birth (odds ratio 2.79), history of lung disease (odds ratio 2.52), previous spontaneous preterm birth (odds ratio 2.45), age >30 years (odds ratio 2.42), black ethnicity (odds ratio 1.56), and working during pregnancy (odds ratio 1.49). Alcohol use in pregnancy was actually associated with a lower risk of indicated preterm birth (odds ratio 0.35). CONCLUSION: The risk factors found in this analysis tend to be different from those associated with spontaneous preterm birth.

Adolescent↗
PubMed1998

The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: We sought to estimate the risk of spontaneous preterm birth in parous women by use of obstetric history, fetal fibronectin, and sonographic cervical length. STUDY DESIGN: The probability of spontaneous preterm birth before 35 weeks' gestation was estimated from a logistic regression model with data from 1282 parous women analyzed according to gestational age at the most recent prior delivery (prior preterm birth at 18 to 26 weeks, 27 to 31 weeks, 32 to 36 weeks, and > or = 37 weeks' gestation), fetal fibronectin status (positive = > or = 50 ng/dl), and cervical length by percentile groups (< or = 10th = < or = 25 nm, 10th to 50th = 26 to 35 mm, and > 50th = > 35 mm) measured at 22 to 24 weeks' gestation. Fibronectin and cervical length results were blinded for clinical care. RESULTS: Among fetal fibronectin positive women with a prior preterm birth, the estimated recurrence risk of preterm birth < 35 weeks' gestation was approximately 65% when the cervix was < or = 25 mm, 45% when the cervix was 26 to 35 mm, and 25% when the cervix was > 35 mm at 24 weeks' gestation. For fetal fibronectin negative women with a prior preterm birth, the recurrence risk was 25% when the cervix was < or = 25 mm, 14% when the cervix was 26 to 35 mm, and 7% when the cervix was > 35 mm. The risk of preterm birth was increased among women with a history of preterm delivery but was not influenced by the gestational age at delivery of the most recent preterm birth. CONCLUSION: The recurrence risk of spontaneous preterm birth varies widely according to fetal fibronectin and cervical length. Cervical length and fetal fibronectin results had distinct and significant effects on the recurrence risk of preterm birth. Predicted recurrence risk is increased by twofold to fourfold in women with a positive compared with a negative fetal fibronectin, and it increases as cervical length shortens in both fetal fibronectin-positive and fetal fibronectin-negative women. These data may be useful to care for women with a history of preterm birth and to design studies to prevent recurrent premature delivery.

Adult↗