Outcome in anorexia nervosa.
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Anorexia Nervosa↗
Biomedical subjects
S Abraham
Publications and source records attributed to S Abraham.
Blocking tumor growth, invasion, and metastasis by maspin in a syngeneic breast cancer model.
Maspin is a unique serine protease inhibitor of which the down-regulation is associated with the development of breast cancers. In vitro, recombinant maspin inhibits tumor cell migration and invasion. Overexpression of maspin in transgenic mice is protective against tumor progression. Additionally, maspin acts as an angiogenesis inhibitor in rat cornea model and in a xenograft tumor model. To additionally prove that maspin is directly involved in the suppression of tumor growth and metastasis, we tested maspin in a new syngeneic mammary tumor model, TM40D. This model involves the implantation of TM40D mammary tumor cells orthotopically to the mammary gland; tumors grew within the gland and then become invasive and metastatic to other organs. Here we demonstrate that TM40D cells in implanted mammary glands are highly invasive. Overall, a 75% rate of invasion and metastasis was observed in this model. However, both primary tumor growth and metastasis were significantly blocked in TM40D cells that overexpress maspin as a consequence of plasmid or retrovirus infection. Maspin-transfected tumors tended to have tumor encapsulation and less necrosis, which were associated with better prognosis and lower invasiveness. Thus, maspin can block primary tumor growth as well as invasion and metastasis. These data support the concept that maspin has a strong protective role against tumor progression.
Animals↗
Type 1 fimbriated Escherichia coli-mast cell interactions in cystitis.
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Caveolae↗
Body mass index, menarche, and perception of dieting among peripubertal adolescent females.
OBJECTIVE: To examine perceptions of dieting among pre and postmenarchial female school students. METHOD: All 51 female students of mean (SD) age 12.6 (0.6) years from a state school volunteered to complete a questionnaire about general health, eating and weight control behaviors, and menstrual status. Height and weight were measured. Focus groups using structured questions and discussion were used to elicit responses about the meaning of dieting and its association with menarche. RESULTS: Postmenarchial females were significantly more likely than the same age premenarchial students to have increased their body mass index (BMI), to clearly articulate the meaning of dieting, to report trying to lose weight, and to use diet and exercise to lose weight. Premenarchial females did not have a clear perception of dieting. Premenarchial females who reported trying to lose weight equated dieting with healthy eating and did not include losing weight or the behaviors and feeling associated with the concept of dieting unless their BMI had increased and menarche was imminent. DISCUSSION: The concept of dieting that may result in weight loss and the behaviors and feelings associated with dieting did not develop until menarche and is likely to be associated with the rapid increase in height, weight, and body fat that precedes menarche. Educational interventions aimed at preventing eating disorders among premenarchial adolescents may therefore be inappropriate, ineffective, and potentially dangerous.
Adolescent↗
Safety and efficacy of repeat transradial access for cardiac catheterization procedures.
To determine the safety and efficacy of repeat transradial cardiac catheterization, 1,362 consecutive transradial procedures were examined. Repeat transradial procedures were identified (group I, n = 73) and compared with index procedures (group II, n = 1,289). Baseline patient characteristics, procedure success rates (100% vs. 97.9%; P = NS), complication rates (0% vs. 0.08%; P = NS), and procedure times (23.9 +/- 27.3 min vs. 18.2 +/- 14.7 min; P = NS) were similar between groups. This study suggests that repeat transradial catheterization procedures can be performed safely and successfully in appropriately selected patients.
Aged↗
Postnatal depression, eating, exercise, and vomiting before and during pregnancy.
OBJECTIVE: To examine the postnatal distress and the eating, exercise, and weight losing behavior of women before and during pregnancy. METHOD: The subjects were healthy women who had given birth to a singleton healthy baby in the week before the study. They were drawn from two consecutive series of mothers of babies whose birth weights were either < or =2,500 g or >2,500 g. A total of 181 women were interviewed using a standardized interview modified for pregnancy and related behaviors. They also completed the Edinburgh Postnatal Distress Questionnaire. RESULTS: Regression analysis produced a final model containing variables that made a unique contribution to predicting the level of distress of women in the week following childbirth. The model accounted for 25% of the variance and included four variables that were associated with greater distress: fear of weight gain before and during pregnancy, being distracted by thoughts of food during pregnancy, being afraid of gaining more weight than the pregnancy would explain, and vomiting more frequently during the first 3-4 months of pregnancy. A fifth variable accounted for less distress, that is, participating in low-intensity exercise for reasons of shape and weight during months 3-4 of pregnancy. Other variables associated with distress only in the preliminary analysis were maternal age, binge eating, and vomiting before pregnancy. The most distressed mothers were suffering from an eating disorder at the time of pregnancy. The binge and/or purge type of eating disorder was associated with more distress than a food restriction type. DISCUSSION: Postnatal distress is associated with body weight and shape concerns, with disordered eating before and during pregnancy, and with vomiting during pregnancy. The protective role of low-intensity exercise during early pregnancy needs to be explored. Women with eating disorders should be considered at risk for postnatal problems.
Adult↗
Detection of Y chromosome-specific DNA in the plasma and urine of pregnant women using nested polymerase chain reaction.
The present study was undertaken to evaluate a nested polymerase chain reaction (PCR) for detection of Y chromosome-specific fetal DNA in maternal plasma and urine of pregnant women during different gestational stages. DNA isolated from plasma and urine samples of 80 pregnant women (between 7 and 40 weeks' gestation) underwent amplification for Y chromosome-specific 198 bp DNA by nested PCR. The postpartum analysis of fetal gender showed that 55 women carried male and 25 female fetuses. Among the 55 women bearing male fetuses, Y chromosome-specific signals were detected in 53 (96%) plasma and 21 (38%) urine samples. Moreover, out of 25 women bearing female fetuses, 3 (12%) and 1 (4%) women had Y chromosome-specific signal in plasma and urine, respectively. Analysis of results with respect to gestational age revealed that there was no significant difference in the detection of Y chromosome-specific DNA between different trimesters in maternal plasma of women bearing male fetuses. These results showed that fetus-specific DNA was detected with high sensitivity (96%) and specificity (88%) in the maternal plasma by nested PCR, and therefore the method could be useful as a non-invasive procedure for fetal sex determination and prenatal diagnosis.
Adult↗
Altered energy metabolism in anorexia nervosa.
Optimal nutritional rehabilitation of anorexia nervosa requires more information concerning actual energy and substrate requirements. To this end, indirect calorimetry was performed in female patients (n=34, age 20.9+/-1.2 yr, body mass index [BMI] 15.6+/-0.2 kg/m(2); mean+/-SEM) soon after commencement of refeeding and at the time of discharge from hospital (n=18, BMI 19.0+/-0.3 kg/m(2)). Healthy female controls (n=18, age 24.6+/-1.3 yr, BMI 21.6+/-0.6 kg/m(2)) were also tested. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured in the fasting state, followed by diet-induced thermogenesis (DIT) and RQ over a 4 h period following a 100 g oral glucose load. Compared with post-refeeding patients and controls, pre-refeeding patients had a high basal RQ and a low REE, with a paradoxically higher DIT (13.2+/-0.9% of REE vs. 8.3+/-1.2% and 8.6+/-0.9% in post-refeeding patients and controls, respectively). RQ values in pre-refeeding patients exceeded unity following the glucose load, probably reflecting net lipogenesis, whereas in the post-refeeding patients, post-glucose RQ was similar to that of controls, suggesting premature curtailment of lipogenesis. These data demonstrate energy wasting in emaciated patients with anorexia nervosa. Biological repair processes could account for disproportionate energy loss early in refeeding and there may be some later impediment to full restoration of fat stores.
Adolescent↗
Effects of specific anti-B and/or anti-plasma cell immunotherapy on antibody production in baboons: depletion of CD20- and CD22-positive B cells does not result in significantly decreased production of anti-alphaGal antibody.
Anti-Galalpha1-3Gal antibodies (antialphaGal Ab) are a major barrier to clinical xenotransplantation as they are believed to initiate both hyperacute and acute humoral rejection. Extracorporeal immunoadsorption (EIA) with alphaGal oligosaccharide columns temporarily depletes antialphaGal Ab, but their return is ultimately associated with graft destruction. We therefore assessed the ability of two immunotoxins (IT) and two monoclonal antibodies (mAb) to deplete B and/or plasma cells both in vitro and in vivo in baboons, and to observe the rate of return of antialphaGal Ab following EIA. The effects of the mouse anti-human IT anti-CD22-ricin A (proportional to CD22-IT, directed against a B cell determinant) and anti-CD38-ricin A (proportional to CD38-IT, B and plasma cell determinant) and the mouse anti-human anti-CD38 mAb (proportional to CD38 mAb) and mouse/human chimeric anti-human anti-CD20 mAb (proportional to CD20 mAb, Rituximab, B cell determinant) on B and plasma cell depletion and antialphaGal Ab production were assessed both in vitro and in vivo in baboons (n = 9) that had previously undergone splenectomy. For comparison, two baboons received nonmyeloablative whole body irradiation (WBI) (300 cGy), and one received myeloablative WBI (900 cGy). Depletion of B cells was monitored by flow cytometry of blood, bone marrow (BM) and lymph nodes (LN), staining with anti-CD20 and/or anti-CD22 mAbs, and by histology of LN. EIA was carried out after the therapy and antialphaGal Ab levels were measured daily. In vitro proportional to CD22-IT inhibited protein synthesis in the human Daudi B cell line more effectively than proportional to CD38-IT. Upon differentiation of B cells into plasma cells, however, less inhibition of protein synthesis after proportional to CD22-IT treatment was observed. Depleting CD20-positive cells in vitro from a baboon spleen cell population already depleted of granulocytes, monocytes, and T cells led to a relative enrichment of CD20-negative cells, that is plasma cells, and consequently resulted in a significant increase in antialphaGal Ab production by the remaining cells, whereas depleting CD38-positive cells resulted in a significant decrease in antialphaGal Ab production. In vivo, WBI (300 or 900 cGy) resulted in 100% B cell depletion in blood and BM, > 80% depletion in LN, with substantial recovery of B cells after 21 days and only transient reduction in antialphaGal Ab after EIA. Proportional to CD22-IT depleted B cells by > 97% in blood and BM, and by 60% in LN, but a rebound of B cells was observed after 14 and 62 days in LN and blood, respectively. At 7 days, serum antialphaGal IgG and IgM Ab levels were reduced by a maximum of 40-45% followed by a rebound to levels up to 12-fold that of baseline antialphaGal Ab by day 83 in one baboon. The results obtained with proportional to CD38-IT were inconclusive. This may have been, in part, due to inadequate conjugation of the toxin. Cell coating was 100% with proportional to CD38 mAb, but no changes in antialphaGal Ab production were observed. Proportional to CD20 mAb resulted in 100% depletion of B cells in blood and BM, and 80% in LN, with recovery of B cells starting at day 42. Adding 150cGy WBI at this time led to 100% depletion of B cells in the BM and LN. Although B cell depletion in blood and BM persisted for > 3 months, the reduction of serum antialphaGal IgG or IgM Ab levels was not sustained beyond 2 days. Proportional to CD20 mAb + WBI totally and efficiently depleted CD20- and CD22-positive B cells in blood, BM, and LN for > 3 months in vivo, but there was no sustained clinically significant reduction in serum antialphaGal Ab. The majority of antibody secretors are CD38-positive cells, but targeting these cells in vitro or in vivo with proportional to CD38-IT was not very effective. These observations suggest that CD20-and CD22-positive B cells are not the major source of antialphaGal Ab production. Future efforts will be directed towards suppression of plasma cell function.
Animals↗
Obstetricians and maternal body weight and eating disorders during pregnancy.
Intrauterine growth restriction (IUGR) is associated with maternal prepregnancy body mass index (BMI), body weight gain during pregnancy and smoking, eating and weight-losing behaviors. The aim of this pilot study was to examine the practices of obstetricians to determine whether more can be done to prevent IUGR and 'do no harm' to the body image of women during pregnancy. Obstetricians (n = 67) who reported delivering an average of 125 babies in the previous year completed a questionnaire that enquired about their antenatal practice of maternal weighing, history taking and referral of pregnant women. No doctor calculated the prepregnancy BMI. Women (90%) were weighed during some or all antenatal visits, usually by the nurse-receptionist, but one-third of the obstetricians did not refer to these body weight records. Most obstetricians asked women about their cigarette smoking and alcohol intake before pregnancy, and during pregnancy discussed supplements and nausea and vomiting. Fewer than 50% of doctors asked about depression, body weight control and disordered eating. One-third of doctors were not aware of having seen a woman with an eating disorder in the previous year. Obstetricians who asked about eating disorders were more likely to ask about depression, and obstetricians in private practice were significantly less likely to ask women about a history of depression and to refer women to a psychologist or psychiatrist Obstetricians could improve antenatal care by asking about body weight and calculating prepregnancy BMI, and investigating weight-losing behavior and psychological or psychiatric problems such as eating disorders.
Adult↗
QTc prolongation and cardiac lesions following acute organophosphate poisoning in rats.
Sarin and soman induced the following similar effects: prolongation of QT interval duration, cardiac lesions and immediate and statistically significant decrease in body weight. However, animals exposed to soman remained underweight and suffered delayed death. Thus, as sarin produced both cardiac lesions and QT prolongation, without exhibiting late death, it is unlikely that the late death observed in soman-poisoned rats are attributable to QT prolongation and the occurrence of life-threatening arrhythmias. It is postulated that low body weight may precipitate late mortality in soman-exposed rats. It is well documented that QT prolongation in the rat is explained in terms of blockade of the Ito potassium channels and the Na+/Ca+2 exchanger. Soman and sarin may exert their effect on QT interval duration through non-specific action on these sites. As drug-induced QT prolongation in man is mediated by blockade of Ikr potassium channels, the data presented in this study may not predict late death in humans in cases of organophosphate intoxication.
Acute Disease↗
Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2.
T-box genes encode a family of phylogenetically conserved DNA-binding proteins that regulate gene expression during embryogenesis. While the developmental importance of many T-box genes has been well documented, little is known about how family members differ in their DNA binding properties and ability to modulate transcription. Here we show that although TBX1, TBX2 and the Xenopus T protein (Xbra) share only 50-60% identity within their DNA-binding domains they can bind the same DNA sequence in vitro. However, the proteins differ in three important respects. While TBX1 protein binds a palindromic T oligonucleotide as a dimer, as had been previously reported for Xbra, TBX2 appears to bind the same DNA sequence as a monomer. Also, T protein/DNA complexes are stabilized in vitro by the addition of specific antibodies, whereas TBX2/DNA complexes are not stabilized by antibodies. Most importantly, TBX2 represses while Xbra activates transcription of the same chimeric reporter plasmid. TBX1, although capable of binding to the chimeric promoter, has no effect on transcription. Thus, while the DNA binding domains of T-box proteins share substantial homology, these proteins differ in both their DNA binding and transcriptional modulation properties. These results suggest that the various T-box proteins, while highly conserved, likely use different mechanisms to modulate transcription and may have different targets in vivo.
Amino Acid Sequence↗
A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues.
We used a subtractive hybridization protocol to identify novel expressed sequence tags (ESTs) corresponding to mRNAs whose expression was induced upon exposure of the human leukemia cell line K562 to the phorbol ester 12-O-tetradecanolyphorbol-13-acetate (TPA). The complete open reading frame of one of the novel ESTs, named TIG-1, was obtained by screening K562 cell and placental cDNA libraries. The deduced open reading frame of the TIG-1 cDNA encodes for a glutamine repeat-rich protein with a predicted molecular weight of 63kDa. The predicted open reading frame also contains a consensus bipartite nuclear localization signal, though no specific DNA-binding domain is found. The corresponding TIG-1 mRNA is ubiquitously expressed. Placental tissue expresses the TIG-1 mRNA 200 times more than the lowest expressing tissues such as kidney and lung. There is also preferential TIG-1 mRNA expression in cells of bone-marrow lineage.In-vitro transcription/translation of the TIG-1 cDNA yielded a polypeptide with an apparent molecular weight of 97kDa. Using polyclonal antibodies obtained from a rabbit immunized with the carboxy-terminal portion of bacterially expressed TIG-1 protein, a polypeptide with molecular weight of 97kDa was identified by Western blot analyses of protein lysates obtained from K562 cells. Cotransfection assays of K562 cells, using a GAL4-TIG-1 fusion gene and GAL4 operator-CAT, indicate that the TIG-1 protein may have transcriptional regulatory activity when tethered to DNA. We hypothesize that this novel glutamine-rich protein participates in a protein complex that regulates gene transcription. It has been demonstrated by Naar et al. (Naar, A.M., Beaurang, P.A., Zhou, S., Abraham, S., Solomon, W.B., Tjian, R., 1999, Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398, 828-830) that the amino acid sequences of peptide fragments obtained from a polypeptide found in a complex of proteins that alters chromatin structure (ARC) are identical to portions of the deduced open reading frame of TIG-1 mRNA.
Amino Acid Sequence↗
Ischaemia selectivity confers efficacy for suppression of ischaemia-induced arrhythmias in rats.
Eight novel and three reference antiarrhythmics were investigated in anaesthetised rats for antiarrhythmic actions, as well as for effects on the electrocardiogram (ECG) under normal and "simulated ischaemic" conditions. In rats subjected to coronary artery occlusion lidocaine, (+/-)-trans-[2-(4-morpholinyl)-cyclohexyl]naphthyl-1-acetate, RSD1000 and (+/-)-trans-[2-(4-morpholinyl)-cyclohexyl]-2-(1-naphthyl)propionate, RSD1030, (Group A) produced dose-related and complete antiarrhythmic protection. Group B compounds, such as (+/-)-trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-3, 4-dichlorocinnamamide, RSD995, produced complete antiarrhythmic protection but had aberrant dose-response curves. Group C compounds, such as quinidine and flecainide, failed to give full antiarrhythmic protection and had shallow dose-response curves. The potency of Group A compounds, but not Group B or C compounds, for ECG actions indicative of Na(+) channel blockade (prolongation of PR and QRS intervals) were significantly increased under "simulated ischaemic" conditions ([K(+)] 10 mM and pH 6.4) in isolated rat hearts. Thus, compounds with ischaemia-selective actions provided superior protection against ischaemia-induced arrhythmias in rats.
Animals↗
Improving the body image, eating attitudes, and behaviors of young male and female adolescents: a new educational approach that focuses on self-esteem.
OBJECTIVE: This study examines the effect of an interactive, school-based, self-esteem education program on the body image and eating attitudes and behaviors of young male and female adolescents following the program and after 12 months. METHOD: All 470 eligible students (63% female) aged 11-14 years volunteered to participate. The intervention group students participated in the program, whereas the control group students received their scheduled personal development and health class. RESULTS: The program significantly improved the body satisfaction of the intervention students and significantly changed aspects of their self-esteem; social acceptance, physical appearance, and athletic ability became less important for the intervention students and more important for control students. Female intervention students rated their physical appearance as perceived by others significantly higher than control students and allowed their body weight to increase appropriately by preventing the age increase in weight-losing behaviors of the control students. One year after the intervention, body image and attitude changes were still present. These findings also held for the 116 students (63% females) with low self-esteem and higher anxiety, who were considered at risk for the development of eating disorders. These students also had significantly lower drive for thinness and greater body satisfaction following the intervention and the decreased importance of physical appearance to their self-esteem was present at 12 months. Control at-risk students significantly decreased their body weight, whereas the weight of the intervention at-risk students significantly increased. The intervention program was effective, safe, having no effect on measures of students' anxiety or depression, and was rated highly by students. DISCUSSION: This is the first controlled educational intervention to successfully improve body image and to produce long-term changes in the attitudes and self-image of young adolescents. This new approach to prevent the development of eating disorders by improving self-esteem may be effective, particularly if reinforced by teachers and family.
Adolescent↗
Gross morphology and ultrastructure of dendritic cells in the normal human decidua.
Five normal placentae of normal pregnancy and delivery were used to study the gross morphology and ultrastructure of the dendritic cells in the normal human decidua. Zinc iodide osmium (ZIO) mixture was prepared. Small pieces of the placenta were processed for light microscopy and electron microscopy. For light microscopy, the small pieces of placenta were incubated in 20 mM PBS-EDTA solution, ph 7.4 at 37 degrees C to detach the basal plate. The basal plate pieces were incubated in ZIO. A wholemount preparation of the basal plate demonstrated the whole profile and gross morphology of the dendritic cell. For electron microscopy, the placenta pieces were fixed in 3% glutaraldehyde in 0.1 M phosphate buffer, ph 7.4, washed with phosphate buffer, put in ZIO mixture, washed in distilled water, dehydrated in graded ethanol, cleared in propylene oxide, and embedded in resin. Ultra thin sections of the ZIO blocks were cut using a diamond knife and stained with lead citrate. Ultrastructure of the dendritic cell presented multiple cytoplasmic processes, lobulated or round or oval, heterochromatic or euchromatic nucleus, mitochondria, free ribosomes, and pieces of rough endoplasmic reticulum, but no Birbeck granules.
Decidua↗
Transradial cardiac catheterization in elderly patients.
The safety and efficacy of transradial cardiac catheterization in elderly patients is unknown. This study examines procedure success rates for transradial catheterization in appropriately selected patients < 70 (n = 195) and >/= 70 (n = 83) years old. Elderly patients were less likely to be selected for the transradial approach (46% vs. 61%; P = 0.05). Although patients >/= 70 years old were more often female (39.7% vs. 24.1%; P = 0.008) and had a smaller body surface area (1.89 +/- 0.18 vs. 2.01 +/- 0.24 m2; P = 0. 001), procedure success rates did not differ (95.1% vs. 94.8%; P = NS). Procedure-related variables including procedure time (15.4 +/- 12.6 vs. 16.1 +/- 11.6 min; P = NS), amount of radiographic contrast (90.1 +/- 31.9 vs. 86.4 +/- 29.8 cc; P = NS), and number of catheters used (1.5 +/- 0.9 vs. 1.5 +/- 0.7; P = NS) were similar between groups. We conclude that transradial catheterization can be safely and effectively performed in selected elderly patients. Cathet. Cardiovasc. Intervent. 51:287-290, 2000.
Adult↗
The reality of unsafe abortion in a rural community in South India.
Though the law in India has permitted medical termination of pregnancy on broad legal grounds for over two decades, unsafe abortions carried out by unqualified providers show no signs of decreasing. A community-based study was undertaken in rural South India to determine the prevalence of induced abortion, women's reasons for seeking abortion, who was providing abortions and whether the procedures were safe or unsafe. A cross-sectional study design was used that included focus group discussions with 88 women and a quantitative survey with 195 married women who had a birth interval of two or more years since their last pregnancy. There was a high prevalence of induced abortion (28 per cent) among the study population, mainly among women who were not using contraception. Most abortions were carried out in the first trimester of pregnancy and unqualified practitioners performed 65 per cent of terminations. The preference for illegal, untrained providers in a country where abortion is legally available exposes the ambiguity in the status of abortion and how inadequacies in legal service provision have served to promote and sustain unsafe providers and practices. An integrated approach to family planning and reproductive health which includes abortion is imperative if the reproductive health status of Indian women is to be improved. The poor utilisation of existing government facilities suggests the need for improving the quality of services, expansion of abortion facilities and the introduction of safer methods of abortion. To do this, a re-examination and re-framing of aspects of the 1971 abortion law is needed.
Abortion, Induced↗