Biomedical subjects

N Vaisman

Publications and source records attributed to N Vaisman.

At least 19 recordsLinked to original sources

PubMed2006

Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent manner.

The insulin-like growth factor-I receptor (IGF-IR) has an important role in colorectal cancer development and progression. IGF-IR displays a potent anti-apoptotic activity and is overexpressed in primary tumors and colon cancer-derived cell lines. Folic acid, a member of the vitamin B family, is a chemopreventive agent whose deficiency has been linked to an enhanced colon cancer risk. The present study was aimed at testing the hypothesis that part of the modulatory effect of folic acid on malignant transformation may be attributed to its ability to regulate IGF-IR gene expression. Regulation of IGF-IR gene expression by folic acid was assessed using western blots, RT-PCR, transient transfections and chromatin immunoprecipitation assays. Activation of the IGF-IR signaling pathway was evaluated by measuring phosphorylation of ERK, and apoptosis was assayed using poly (ADP-ribose) polymerase cleavage and annexin V-FITC staining. Results obtained showed that folic acid induced a dose-dependent decrease in IGF-IR protein and mRNA levels in the HCT116 +/+ colon cancer cell line. This effect was associated with a significant reduction in IGF-IR promoter activity. Similar effects were elicited by the folic acid metabolites dihydrofolic acid and tetrahydrofolic acid. In addition, folic acid abrogated the IGF-I-stimulated phosphorylation of the downstream signaling molecule ERK1/2 and exhibited a pro-apoptotic activity. Moreover, folic acid induced a significant decrease in Sp1 binding to the IGF-IR promoter region. Finally, folic acid had no effect in wild-type p53-depleted HCT116 -/- and Caco-2 cells. In conclusion, the mechanism of action of folic acid involves regulation of IGF-IR gene expression. The ability of folic acid to downregulate the IGF-I signal transduction pathway may allow the micronutrient to function as a chemopreventive agent. Folic acid deficiency, on the other hand, may lead to increased IGF-IR gene expression, with ensuing pathological activation by endocrine and/or autocrine/paracrine IGF-I.

Apoptosis↗

PubMed2004

Correction of anemia in patients with congestive heart failure increases resting energy expenditure.

BACKGROUND & AIM: Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF. PATIENTS AND METHODS: Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls. RESULTS: After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively). CONCLUSION: Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake.

Aged↗

PubMed2004

Increased resting energy expenditure in subjects with Emery-Dreifuss muscular dystrophy.

We have studied changes in energy expenditure and body composition in adult males with Emery-Dreifuss muscular dystrophy, age-matched males with hyperCKemia and age-matched healthy controls. All participants were studied twice, 2-3 years apart. Resting energy expenditure was studied by indirect calorimetry, lean body mass and body fat by dual X-ray absorptiometry, and muscle mass was estimated based on 24-h urinary creatinine excretion. At baseline and 2-3 years later, body fat was significantly higher (P < 0.011 and P < 0.003, respectively) and lean body mass significantly lower (P < 0.024 and P < 0.012, respectively) in patients with Emery-Dreifuss muscular dystrophy as compared to subjects with hyperCKemia and healthy controls. Resting energy expenditure, over the study period, increased significantly in patients with Emery-Dreifuss muscular dystrophy (P < 0.031), but not in patients with hyperCKemia nor in healthy controls. Our study suggests that patients with Emery-Dreifuss muscular dystrophy may have increased energy expenditure relative to healthy subjects. If not met by increased caloric intake, this greater energy expenditure may partially contribute to a further deterioration in their muscle performance.

Absorptiometry, Photon↗

PubMed2004

Nasojejunal feeding in hyperemesis gravidarum--a preliminary study.

Hyperemesis gravidarum is a severe form of nausea and vomiting during the first trimester of pregnancy. Our objective was to assess the feasibility of nasojejunal feeding in our patients. Eleven pregnant women aged 23-46 years with hyperemesis gravidarum, persisting in spite of an in-hospital treatment of 2-15 days by intravenous fluids and antiemetic drugs and accompanied by weight loss, consented to have a nasojejunal feeding tube inserted endoscopically. Mean in-hospital weight loss prior to tube insertion was 2.2+/-1.1 kg (range 0.9-5.1 kg). A clear reduction in the extent of vomiting was already apparent within the first 48 h after tube insertion, but vomiting ceased completely after a mean of 5+/-4 days (range 1-13 days). Weight gain was recorded in six patients who stayed on tube feeding for more than 4 days. Patients were encouraged to start drinking and eating along tube feeding after 3-4 days. Ceasing vomiting and a concomitant sufficient oral intake of at least 1000 kcal/day resulted in the decision to remove the tube after 4-21 days. In three cases, however, the tube was expelled by recurrent vomiting after 1-4 days, or was blocked as in one case. The tube was not reintroduced and patients did not resume vomiting. There were no complications associated with this feeding approach in this population. Only one patient was readmitted. None of the rest resumed vomiting after tube withdrawal.The above suggests that nasojejunal enteral feeding can be an effective option in hyperemesis gravidarum persisting despite intravenous fluids and antiemetic drugs.

Adult↗

PubMed2000

Specific inhibition of the reaction between a tumor-inhibitory antibody and the ErbB-2 receptor by a mimotope derived from a phage display library.

Overexpression of ErbB-2, a coreceptor for stroma-derived growth factors, is involved in malignancies of epithelial tissues, and a humanized antibody to ErbB-2 was shown to be therapeutic in a clinical setting. In an effort to understand and enhance immunotherapy, the laboratory has raised several tumor inhibitory monoclonal antibodies (mAb), including mAb L26 that blocks inter-receptor interactions. Here the application of the phage display methodology for the isolation of a phage clone that specifically recognizes mAb L26 is described. The isolated mimetic peptide (mimotope) specifically inhibited the binding of mAb L26 to ErbB-2 overexpressing cells. No sequence homology was found between the mimotope and ErbB-2. implying that it mimics a conformational structure of the receptor. Preliminary studies showed that the lead peptide can be truncated by removal of two to three amino acids from either the N- or C-terminal end without drastically affecting the inhibitory properties of the mimotope. A tryptophan'glycine residue at the C-terminus and a lysine at the N-terminus of the peptide seemed to play a role in its ability to compete with L26 antibody for binding to ErbB-2 overexpressing cells. These results highlight the potential of active immunization with conformation mimicking peptides in ErbB-2 overexpressing tumors.

Amino Acid Sequence↗

PubMed1999

Immunogenicity of H-2Kb-low affinity, high affinity, and covalently-bound peptides in anti-tumor vaccination.

CTL induction by immunization with synthetic peptide epitopes has been shown to inhibit tumor growth and its metastatic spread. Ex vivo pulsing of peptides on MHC class I-bearing cells such as RMA-S cells or professional APCs elicits an effective CTL response. Since the stability of the MHC-peptide complex is strongly correlated with the overall immunogenecity, we compared the effect of immunization with low affinity, high affinity, and irreversibly bound MHC peptides in the context of immunotherapy of metastasis. MUT1, a tumor-associated antigen peptide that was isolated from 3LL Lewis lung carcinoma, is a low H-2Kb binder. MUT1 was modified into a high binder by changing positions 3, 5, and 8 to the favorable anchor residues. In addition, we introduced a photo-active chemical moiety, which can bind irreversibly to MHC upon illumination. These peptides, loaded onto RMA-S, were used to immunize mice against the 3LL tumor. Vaccination via the covalent conjugation of the low binder peptide was found to increase the CTL response measured against MUT1 loaded cells and against H-2Kb transfected D122 cells relative to the native MUT1 peptide. However, the photo cross-linking of the high affinity peptide to the MHC did not significantly improve the induction of specific CTL. The level of CTL activity was elevated to the same extent by either cross-linking the peptide to the MHC or by modifying it into a high-binder peptide. The protective capacity of all the peptide-based vaccines against D122 metastatic spread to the lungs was found to be comparable. These results indicate that augmentation of the affinity of a TAA peptide to the RMA-S surface MHC molecules, by conversion to a high-affinity mimotope or by photo-conjugation, can significantly enhance the immune response. There seems to be, however, a ceiling beyond which increase in the peptide-binding affinity does not lead to a corresponding enhancement of the overall immunogenicity of the peptide.

Animals↗

PubMed1999

The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors.

The erbB-2/HER2 oncogene is overexpressed in a significant fraction of human carcinomas of the breast, ovary, and lung in a manner that correlates with poor prognosis. Although the encoded protein resembles several receptors for growth factors, no high affinity ligand of ErbB-2 has so far been fully characterized. However, several lines of evidence have raised the possibility that ErbB-2 can augment signal transduction initiated by binding of certain growth factors to their direct receptors. Here, we contrasted these two models of ErbB-2 function: First, examination of a large series of epidermal growth factor (EGF)-like ligands and neuregulins, including virus-encoded ligands as well as related motifs derived from the precursor of EGF, failed to detect interactions with ErbB-2 when this protein was singly expressed. Second, by using antibodies that block inter-ErbB interactions and cells devoid of surface ErbB-2, we learned that signaling by all ligands examined, except those derived from the precursor of EGF, was enhanced by the oncoprotein. These results imply that ErbB-2 evolved as a shared receptor subunit of all ErbB-specific growth factors. Thus, oncogenicity of ErbB-2 in human epithelia may not rely on the existence of a specific ligand but rather on its ability to act as a coreceptor for multiple stroma-derived growth factors.

Breast Neoplasms↗

PubMed1999

Gastric emptying in patients with type I diabetes mellitus.

Diabetic autonomic neuropathy is a known complication of long-standing diabetes. The present study was designed to study the prevalence of asymptomatic prolonged gastric emptying (GE) in young patients with IDDM and its correlations with disease duration and autonomic nerve function. The study population included 40 poorly controlled patients, mean age 17.6 +/- 4.6 years, with a disease duration of 1-17.5 years, and 20 age- and sex-matched controls. Autonomic nerve functions were assessed by standard cardiovascular reflexes, and gastrointestinal (GI) symptoms were assessed by a detailed questionnaire. GE was assessed by electrical impedance tomography (EIT), at 2 hours after a standard semisolid meal. Mean half-time gastric emptying was significantly prolonged in diabetic patients, 54.80 +/- 26.63 versus 40.37 +/- 8.62 min (p < 0.05), with a higher prevalence in the first 3 years and after 10 years of disease duration. No differences were found between diabetics and controls regarding cardiovascular tests. No correlations were found between age, GI scores, cardiovascular tests, and GE. Patients with IDDM may suffer from prolonged GE. This is not always accompanied by autonomic impairments. As impaired gastric emptying may involve poor glycemic control and early satiety, patients with difficulties in metabolic control or poor caloric intake should be studied for the possibility of delayed gastric emptying.

Adolescent↗

PubMed1998

Efficient initiation of S-phase in yeast requires Cdc40p, a protein involved in pre-mRNA splicing.

The S. cerevisiae CDC40 gene was originally identified as a cell-division-specific gene that is essential only at elevated temperatures. Cells carrying mutations in this gene arrest with a large bud and a single nucleus with duplicated DNA content. Cdc40p is also required for spindle establishment or maintenance. Sequence analysis reveals that CDC40 is identical to PRP17, a gene involved in pre-mRNA splicing. In this paper, we show that Cdc40p is required at all temperatures for efficient entry into S-phase and that cell cycle arrest associated with cdc40 mutations is independent of all the known checkpoint mechanisms. Using immunofluorescence, we show that Cdc40p is localized to the nuclear membrane, weakly associated with the nuclear pore. Our results point to a link between cell cycle progression, pre-mRNA splicing, and mRNA export.

Cell Cycle Proteins↗

PubMed1997

A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks crosstalk with growth factor receptors.

ErbB-2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor (EGF) or Neu differentiation factor (NDF/neuregulin). Because overexpression of the erbB-2 proto-oncogene is frequently associated with an aggressive clinical course of certain human adenocarcinomas, the encoded protein is an attractive target for immunotherapy. Indeed, certain monoclonal antibodies (mAbs) to ErbB-2 effectively inhibit tumor growth in animal models and in clinical trials, but the underlying mechanism is incompletely understood. To study this question, we generated a large battery of mAbs to ErbB-2, that were classified epitopically. Whereas most antibodies stimulated tyrosine phosphorylation of ErbB-2, their anti-tumor effect correlated with its accelerated endocytic degradation. One group of tumor-inhibitory mAbs (Class II mAbs) was elicited by the most antigenic site of ErbB-2, and inhibited in trans binding of NDF and EGF to their direct receptors. The inhibitory effect was due to acceleration of ligand dissociation, and it resulted in the reduction of the ability of ErbB-2 to transactivate the mitogenic signals of NDF and EGF. These results identify two potential mechanisms of antibody-induced therapy: acceleration of ErbB-2 endocytosis by homodimerization and blocking of heterodimerization between ErbB-2 and growth factor receptors.

Animals↗

PubMed1996

Weight perception of adolescent dancing school students.

OBJECTIVE: To study the hypothesis that underweight may be more prevalent among dancing school students than among nondancing school girls, and that their teachers and peers may play a role in developing this tendency. DESIGN: A case-control study on a convenience sample. SETTING: Two local dancing schools and one neighboring regular school. PARTICIPANTS: Forty ballet students, aged 13 to 17 years, from four classes and 29 age-matched girls in four regular classes. INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: Each pupil was asked to classify herself and her peers as underweight, normal, or overweight; teachers were asked to classify their pupils by the same categories. Results were compared with an objective score, weight as a percentage of ideal weight for height, in which less than 85% indicates underweight; 85% to 115%, normal; and more than 115%, overweight. A higher prevalence of underweight as well as a significant tendency to overestimate self-evaluation was found among dancing students. Dancing teachers' evaluation tended to be inaccurate, especially regarding their underweight students. CONCLUSIONS: The atmosphere in dancing classes may encourage striving for thinness beyond normal limits. Ballet teachers may play a significant role in this process. We suggest that physicians and nutritionists be involved in ballet schools.

Adolescent↗

PubMed1996

Effect of breakfast timing on the cognitive functions of elementary school students.

OBJECTIVE: To study the effect of breakfast timing on selected cognitive functions of elementary school students. DESIGN: A 2-week randomized control intervention trial. SETTING: Five elementary schools. SUBJECTS: The subjects comprised 569 children, 51% of them boys, aged 11 to 13 years; the children were in grades 5 through 6 (17 classes). The subjects lived in different areas and had different socioeconomic backgrounds. INTERVENTION: Each subject was tested twice, by 2 versions of the Rey Auditory-Verbal Learning Test, 2 alternative forms of the logical memory subtest of the revised Wechsler Memory Scale, and 2 versions of the Benton Visual Retention Test. On the first test, before any nutritional intervention, the subjects were asked to complete a questionnaire about their food intake on the day of testing. Two thirds of the subjects received 200 ml of 3%-fat milk and 30 g of sugared cornflakes for the next 14 days, and all the subjects were reexamined on the 15th day. MAIN OUTCOME MEASURE: Scoring on the different tests was compared with baseline scores. RESULTS: After 15 days, children who ate breakfast at school scored notably higher on most of the test modules than did children who ate breakfast at home and children who did not at breakfast. CONCLUSIONS: Our results indicate that routinely eating breakfast 2 hours prior to being tested does not improve cognitive functions in 11- to 13-year-old elementary school students, but food supplementation 30 minutes prior to taking a test notably improves scoring. We suggest further studies on the relationship between meal content, feeding time, and scholastic performance.

Adolescent↗

PubMed1996

Impaired brainstem auditory evoked potentials in patients with cystic fibrosis.

Brainstem auditory evoked potentials (BAEPs) were measured in 11 young patients with cystic fibrosis (CF). Though none had clinical evidence of neurological impairment, all had various abnormal components of brainstem auditory evoked potentials (BAEPs). Abnormal BAEPs may be attributed to nutritional deficiencies including deficiencies of vitamins E and B6. As patients with CF are often deficient in vitamin E despite daily supplementation and normal serum levels, the authors suggest that the abnormal BAEPs demonstrated in the present study may reflect prolonged intracellular vitamin E deficiency. This finding suggests that BAEP studies may be useful in the neurological evaluation of patients with CF.

Case-Control Studies↗

PubMed1996

Defective in vitro granulopoiesis in patients with anorexia nervosa.

Patients with anorexia nervosa (AN) frequently suffer from a mild degree of anemia and from moderate leukopenia on top of their undernourished state and metabolic disarrangements. To evaluate in vitro granulopoiesis and its relationship to cytokine production and undernutrition, we have studied 10 adolescent girls with moderate AN (age range, 13.5-18.0). Study methods included assessment of peripheral blood (PB) granulocyte-macrophage colony-forming cells (GM-CFC) of the patients and age-matched controls, and determination of plasma and conditioned medium (CM) of mononuclear cells levels of IL-1, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF), all of which may play a role in GM-CFC growth regulation. GM-CFC numbers were significantly lower in AN patients compared with the normal controls (13.09 +/- 11.15 versus 39.33 +/- 26.61 colonies/5 x 10(5) cells, p < 0.01). No inhibitory effect was found in either plasma or CM of patients with AN. However, when CM were applied to non-recombinant human GM-CSF-stimulated normal bone marrow GM-CFC targets, the number of colonies stimulated by the CM of patients with AN was significantly lower than those stimulated by the CM of the controls (73.5 +/- 20.1 versus 113.0 +/- 11.6, p < 0.025). GM-CSF concentrations in CM were significantly lower in patients with AN compared with normal controls, but no such differences were found in IL-1, IL-3, IL-6, or TNF concentrations. These results indicate defective in vitro granulopoiesis in AN patients, manifested by a reduction of both GM-CFC and GM-CSF. It has to be determined whether these changes are the result of the basic disease process or are they due to malnutrition.

Adolescent↗

PubMed1995

The role of Saccharomyces cerevisiae Cdc40p in DNA replication and mitotic spindle formation and/or maintenance.

Successful progression through the cell cycle requires the coupling of mitotic spindle formation to DNA replication. In this report we present evidence suggesting that, in Saccharomyces cerevisiae, the CDC40 gene product is required to regulate both DNA replication and mitotic spindle formation. The deduced amino acid sequence of CDC40 (455 amino acids) contains four copies of a beta-transducin-like repeat. Cdc40p is essential only at elevated temperatures, as a complete deletion or a truncated protein (deletion of the C-terminal 217 amino acids in the cdc40-1 allele) results in normal vegetative growth at 23 degrees C, and cell cycle arrest at 36 degrees C. In the mitotic cell cycle Cdc40p is apparently required for at least two steps: (1) for entry into S phase (neither DNA synthesis, nor mitotic spindle formation occurs at 36 degrees C and (2) for completion of S-phase (cdc40::LEU2 cells cannot complete the cell cycle when returned to the permissive temperature in the presence of hydroxyurea). The role of Cdc40p as a regulatory protein linking DNA synthesis, spindle assembly/maintenance, and maturation promoting factor (MPF) activity is discussed.

Amino Acid Sequence↗

PubMed1995

Retinoid metabolism in human leucocytes.

Leucocytes from subjects from 0 to 80 years old were separated into mononuclear and granulocyte fractions and the retinoids and retinoid-binding fractions were examined. Both leucocyte fractions were found to contain retinol, retinoic acid and an additional retinoid; retinoic acid comprised 40% of retinoids in some samples. The protein fractions containing retinoids included a 200 kDa protein and several 14-18 kDa proteins. Plasma concentrations of retinol changed little with increasing age. In contrast, leucocyte concentrations of retinoids and retinoid-binding proteins increased quadratically with age. However, in granulocytes from young children retinoids were almost undetectable.

Adolescent↗

PubMed1995

Resting energy expenditure in patients with thalassemia major.

The effect of non-iron-deficiency anemia was studied in seven patients with thalassemia major (beta thalassemia) ages 22-30 y. Each patient was studied before and 3 days after blood transfusion. Hemoglobin concentrations increased significantly after blood transfusion (111-153 vs 81-102 g/L, P < 0.02). Heart rate decreased from 96 +/- 12 to 81 +/- 7 beats/min (mean +/- SD; P < 0.05). No significant difference was found in venous blood pH, bicarbonate concentrations, or lactic acid concentrations before and after blood transfusion. Resting energy expenditure (REE) was greater before blood transfusion in absolute numbers and as a percentage of the predicted value, and returned to normal range thereafter (6138 +/- 112 vs 5678 +/- 738 kJ.kg-1.d-1 and 111.7 +/- 11.3% vs 103.2 +/- 7.8%, respectively). Protein contribution to REE was low before blood transfusion (9.7 +/- 4.2%) and returned to normal range thereafter (15.3 +/- 5.2%) (P < 0.09). This finding may indicate that increased protein turnover as well as increased cardiac work contribute to the observed increase in REE.

Adult↗

PubMed1994

Changes in body composition of children with chronic renal failure during growth hormone treatment.

Growth hormone (GH) has different known metabolic effects, among which are lipolysis and anabolic action. We have studied the changes in body composition of children with chronic renal failure (CRF) after 1 year of daily treatment with GH. Body fat percentage and fat body mass (FBM) were derived from four site skinfold measurements; lean body mass (LBM) from total body potassium (TBK) and mid-arm muscle circumference (MAMC); bone mineral density (BMD) was measured by dual photon absorptiometry. GH treatment had a positive effect on weight, height and MAMC, but no effect on LBM (as reflected by TBK), FBM and BMD. Z-scores were derived in order to compare subjects with a normal population. While no significant change in z-score was noticed for weight, height, MAMC, FBM and BMD, TBK decreased during treatment. We conclude that GH therapy does not ultimately increase LBM in CRF patients compared with other GH-treated groups.

Body Composition↗