Biomedical subjects

N Yerushalmi

Publications and source records attributed to N Yerushalmi.

11 recordsLinked to original sources

PubMed2001

ERGL, a novel gene related to ERGIC-53 that is highly expressed in normal and neoplastic prostate and several other tissues.

We have identified a new gene, that is highly expressed in normal and neoplastic prostate, and is also expressed in cardiac atrium, salivary gland, spleen and selective cells in the CNS. Database analyses of ESTs indicated prostate specificity but experimental results showed the expression in other tissues. The full length transcript is 1800 bp with an open reading frame of 526 aa. The amino-terminal 230 residues of the expressed protein has high homology to a family of lectins, especially to the sugar binding domain of ERGIC-53. We therefore designate the new gene ERGL (ERGIC-53-like). There is a transmembrane domain at amino acid positions 468-482 suggesting that the product of ERGL is a type-I membrane protein. In prostate there are two fully processed transcripts one of which is a splice variant with a deletion in the region of the transmembrane domain of the protein.

Amino Acid Sequence↗

PubMed2001

Seasonal variations in dietary intake affect the consistency of dietary assessment.

BACKGROUND: Nutritional epidemiology studies are usually based on one dietary assessment without taking into account the season in which the interview is taken or adjusting for the difference in reporting dietary intake in different seasons. The semiquantitative food frequency questionnaire has become the primary questionnaire method for measuring dietary intake in epidemiological studies. The aims of this report were (a) to evaluate the effect of season on dietary intake as measured by a semiquantitative food frequency questionnaire (FFQ) conducted twice: once in summer and a second time in winter; and (b) to assess the effect of the differences in dietary intake on biochemical and anthropometric seasonal related changes, such as serum cholesterol and body mass index (BMI). POPULATION AND METHODS: The study population consisted of 94 male industrial employees who participated in clinical biochemical and physical examinations as well as evaluation of their dietary intake twice a year. Dietary intake was assessed using the semiquantitative FFQ that included 96 items and was conducted by a personal interview. RESULTS: We found a significant increase in the intake of selected nutrients in winter as compared to summer as well as an increased intake of animal fat-containing foods such as meat and dairy products. Significant correlation coefficients were shown between the increase in dietary intake of saturated fat and the increase in BMI, serum total and LDL cholesterol. The increase in dietary cholesterol was significantly and positively correlated with the increase in serum total and LDL cholesterol. CONCLUSION: Although FFQ are designed to assess average yearly food intake, we identified significant seasonal changes in dietary intake as measured by FFQ. These changes have a health impact on our population.

Adult↗

PubMed2000

Attenuating the growth of tumors by intratumoral administration of DNA encoding Pseudomonas exotoxin via cationic liposomes.

A gene therapy approach was taken to inhibit tumor growth by transfecting tumor cells with a plasmid encoding a truncated but active form of Pseudomonas exotoxin A (PE), using cationic lipids as the transfection reagent. Cells transfected with this plasmid express PE intracellularly and undergo apoptosis. Transfection was optimized in vitro using two cationic lipids, DOGS and DOSPER. A ratio of between 1:4 and 1:10 (wt/wt) was found to be optimal for DOSPER, and the ratio 1:4 was used for the in vivo study when a smaller injection volume was desired. Estimating the activity of the PE-encoding plasmid was done both directly, by counting cells in vitro after transfection, and by using a cytotoxicity assay, and indirectly, by cotransfecting the plasmid with a plasmid carrying a reporter beta-galactosidase gene and observing a reduction in beta-galactosidase activity with increasing amounts of the PE-encoding plasmid. The cotransfection method was found to be very sensitive, and showed transfection of cells even with 1-2 ng of the PE-encoding plasmid per 10(5) cells. Complexes of the PE-encoding plasmid together with cationic lipid were injected into tumor xenografts in athymic nude mice. The tumor growth of transfected tumors was attenuated compared with control untreated tumors or tumors transfected with a nontoxin-expressing vector. These results indicate the potential of such a treatment for attenuating solid tumor growth in vivo.

ADP Ribose Transferases↗

PubMed1999

An scFv phage clone that binds to human beta2-microglobulin.

Using phage display technology, a novel mouse scFv phage clone D1 was generated from mice immunized with single-chain HLA-A2, the human MHC class I molecules. D1 recognized a determinant in beta2-microglobulin. It reacted with beta2-microglobulin associated with the heavy chain of HLA-A2, recombinant beta2-microglobulin made in Escherichia coli or beta2-microglobulin prepared from human urine. The heavy chain variable region of D1 belongs to gene family VII and the light chain variable region belongs to the kappa chain gene family XI according to the Kabat database.

Amino Acid Sequence↗

PubMed1999

Changes in dietary intake account for seasonal changes in cardiovascular disease risk factors.

OBJECTIVES: (1) to compare dietary intake in summer and winter time; (2) to measure the change in body mass index (BMI), blood pressure and serum cholesterol between winter and summer; and (3) to determine the relationships between seasonal differences in dietary intake and BMI, blood pressure and serum cholesterol measurements. SUBJECTS AND METHODS: Ninety-four male industrial employees were screened twice in one year, in their work place, at winter and summer time. Workers were recruited from two factories and response rate was 95%. Health-related variables, including dietary intake, blood pressure and serum cholesterol were evaluated at each season and were compared. Correlation coefficients between seasonal differences in dietary intake and in BMI, blood pressure and serum cholesterol were calculated. RESULTS: From summer to winter the mean values of BMI increase from 26.1 kg/cm2 to 26.6 (P=0.038), systolic blood pressure from 119.6 to 121.6 (P=0.025), diastolic blood pressure from 75.2 to 77.2 mmHg (P=0.001), total cholesterol from 200.8 to 208.6 mg/dL (P=0.001), LDL cholesterol from 125.2 to 134.9 (P=0.001) and HDL cholesterol from 42.7 to 44.3 (P=0.0084). Triglycerides levels decrease from 174 to 145 in the winter (P=0.03). Mean dietary intake of fat increases from 99.1 to 106.0 (P=0.0016), saturated fat from 43.6 to 46.3 (P=0.0137), polyunsaturated fat from 25.1 to 28.3 (P=0.0002), cholesterol from 462.0 to 497.9 (P=0.0313), sodium from 5778.5 to 8208.2 (P=0.0035), zinc from 11.6 to 12.3 (P=0.0001), vitamin B1 from 1.4 to 1.5 (P=0.002), vitamin D from 4.3 to 4.9 (P=0.0323) and vitamin E from 11.2 to 12.7 (P=0.0073). Significant correlation was shown between the seasonal increase in saturated fat and the increase in BMI (r=0.37), total cholesterol (r=0.21) and LDL cholesterol (r=0.29). Seasonal change in dietary cholesterol intake was significantly and positively correlated with serum total cholesterol (r=0.24) and LDL cholesterol (r=0.24). Blood pressure was not associated with nutritional intake variables. CONCLUSIONS: Dietary intake in summer and winter is different as well as blood pressure, BMI and serum cholesterol. The seasonal increase in fat and cholesterol intake at winter time is associated with changes in BMI and serum cholesterol.

Adult↗

PubMed1998

PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus.

We have used a combination of computerized database mining and experimental expression analyses to identify a gene that is preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus, and placenta, as well as in prostate cancer, testicular cancer, and uterine cancer. This gene is located on the human X chromosome, and it is homologous to a family of genes encoding GAGE-like proteins. GAGE proteins are expressed in a variety of tumors and in testis. We designate the novel gene PAGE-1 because the expression pattern in the Cancer Genome Anatomy Project libraries indicates that it is predominantly expressed in normal and neoplastic prostate. Further database analysis indicates the presence of other genes with high homology to PAGE-1, which were found in cDNA libraries derived from testis, pooled libraries (with testis), and in a germ cell tumor library. The expression of PAGE-1 in normal and malignant prostate, testicular, and uterine tissues makes it a possible target for the diagnosis and possibly for the vaccine-based therapy of neoplasms of prostate, testis, and uterus.

Amino Acid Sequence↗

PubMed1998

Calcitropic hormones and occupational lead exposure.

The authors sought to clarify in a cross-sectional study the possible associations between homeostatic regulators of calcium and occupational exposure to lead. Subjects were 146 industrial male employees, 56 with and 90 without occupational lead exposure. The main outcome measures were serum concentration of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol). The median values of blood lead were 40.5 microg/dl in the exposed group and 4.0 microg/dl in the controls. There were no differences between groups in dietary history and serum calcium levels. PTH and calcitriol levels were significantly higher in the exposed than in the nonexposed subjects (42.0+/-24.2 vs. 33.6+/-14.9 pg/ml, p <0.05; and 83.8+/-27.0 vs. 67.9+/-17.6 pmol/liter, p <0.001, respectively). Multivariate analyses showed that after controlling for possible confounders, occupational lead exposure (no/yes) was independently associated with PTH level (pg/ml) (beta = 7.81, 95% confidence interval (CI) 3.7-11.5) and with calcitriol (pmol/liter) (beta = 12.3, 95% CI 3.84-20.8). It is concluded that subjects occupationally exposed to lead show a substantial compensatory increase in PTH and calcitriol activities which keep serum calcium levels within normal range. This may be of clinical significance since a sustained increase in calcitropic hormones in susceptible subjects may eventually increase the risk of bone disorders.

Adult↗

PubMed1998

Hyaluronic acid-modified bioadhesive liposomes as local drug depots: effects of cellular and fluid dynamics on liposome retention at target sites.

Bioadhesive liposomes, in which hyaluronic acid is the surface-anchored bioadhesive ligand, are being tested in vitro in order to evaluate their bioadhesivity. The first part of the test, binding to monolayers of cells modeling the in vivo designated sites under static conditions, was reported in a previous communication. This communication reports the results of the second and third parts of the test, which consist of evaluating the retention of bound liposomes in the face of tissue-related events such as cell migration, proliferation, and death, and under fluid flow. The in vivo-designated binding sites for the bioadhesive liposomes were modeled, as before, by monolayers of the A431 cell line served. A setup for perfusing a culture flask containing a monolayer of cells was devised for measuring the retention under fluid flow. The major findings are: (1) Over a selected tested period of 28 h, the cell cultures mimicked the tissue-related events described above, whether they did or did not receive a dose of liposomes. Over the same period and throughout these events, the bioadhesive liposomes remained bound at equilibrium-like levels, in the range of 0.03 ng lipid/10(5) cells. (2) Fluid flowed over a cell monolayer dosed with bioadhesive liposomes swept away part of the dose. This loss was due mostly to that fraction of the dose which was in excess of the binding capacity of the monolayer, and occurred over the first 15 min of flow. Thereafter, the cell monolayer retained the bound liposomes, at equilibrium-like levels and with no further loss, even for the longest flow period tested (45 min of continuous flow) and under a flow rate of 0.64 ml/min. This study, together with previous results, shows that the hyaluronic acid-modified liposomes meet all parts of the bioadhesivity test. We therefore find merit in their further investigation.

Animals↗

PubMed1998

Effect of dietary calcium on blood lead concentrations in occupationally exposed and nonexposed workers.

Workers exposed to lead may benefit from a calcium-rich diet, since calcium competes with lead for intestinal absorption. We studied the effect of dietary calcium on blood lead levels. We assessed blood lead levels, dietary intake of calcium, smoking and alcohol consumption, and anthropometric and demographic data in 56 workers exposed to lead and 90 workers without such exposure. Mean intake of dietary calcium was 775 +/- 370 mg/day in the nonexposed workers and 858 +/- 423 mg/day in the exposed workers. Occupational lead exposure explained nearly 90% of the variance in blood lead levels of the entire cohort. Smoking and alcohol intake also showed significant associations with blood lead levels, but their combined effect was less than 2%. When the exposed and nonexposed workers were considered separately, no association was found between blood lead levels and calcium intake. The amount of calcium in the diet does not influence blood lead levels. Further studies are warranted to determine whether dietary calcium influences blood lead levels in exposed and nonexposed workers in other settings and in subjects with lower intakes of calcium.

Adult↗

PubMed1994

Bioadhesive, collagen-modified liposomes: molecular and cellular level studies on the kinetics of drug release and on binding to cell monolayers.

Liposomes, modified by covalently-anchoring collagen to their surface, were investigated for their abilities to be bioadhesive and to act as sustained-release drug carriers. These bioadhesive liposomes have the potential to induce significant improvements in topical and regional therapies. The major findings for uni-(ULV) and multilamellar (MLV) bioadhesive liposomes are: (a) Both ULV and MLV release small molecular weight drugs over prolonged periods. For example, rate constants of (6 +/- 0.5) x 10(-3) and (2.6 +2- 0.8) x 10(-3) h-1, were obtained for the release of vinblastine and fluconazole, respectively, from collagen-ULV. (b) For a given drug, that rate constant can be shifted (up or down) by the choice of liposome type and collagen-surface density and the latter, if high enough, lead to the formation of an additional liposome-associated drug reservoir. (c) Using monolayers of the A431 cell line to model the in vivo targets, the bioadhesive (but not the regular) liposomes were found to bind with high affinity to the monolayers. For example, equilibrium dissociation constants of 6.3(+/- 3) microM and 2.7(+/- 0.5) microM were determined for bioadhesive MLV and ULV, respectively, with corresponding saturation occupancies of 3.7(+/- 1) and 4.0(+/- 0.2) pmoles liposomal collagen/monolayer of 10(5) cells. (d) Following the retention of bioadhesive MLV at A431 monolayers for 24 h, it was found that: at 4 degrees C, 24 h did not suffice to reach equilibrium, but at 37 degrees C equilibrium binding was obtained within 3-5 h and there was quantitative liposome retention (per viable monolayer) thereafter. It is concluded that these liposomes are bioadhesive sustained-release carriers, as desired, meriting further cellular and in vivo studies.

Binding Sites↗

PubMed1994

Molecular and cellular studies of hyaluronic acid-modified liposomes as bioadhesive carriers for topical drug delivery in wound healing.

Liposomes, modified into bioadhesive systems by the covalent anchoring of hyaluronic acid (HA) to their surface, were investigated for their abilities to act as site-adherent and sustained-release carriers of drugs for the topical therapy of wounds and burns. Epidermal growth factor (EGF) served as the test drug for growth factors and monolayers of the A431 cell line served as models of the in vivo designated targets. The hyaluronic acid was radiolabeled to carry 3H, through a deacetylation-reacetylation procedure, yielding specific activities in the range of 1 x 10(6) dpm/mg. The HA was bound to the surface of the liposomes, using carbodiimide to crosslink its carboxyl residues to amine residues at the liposomal surface. The latter was provided through the inclusion of phosphatidylethanolamine in the liposome formulation. Varying the initial HA/lipid ratio over the range 1-500 mg HA/mmol lipid, it was found that the increase in bound HA was linear, providing up to 80 mg HA/mmol lipid. The HA-modified, but not the nonmodified, liposomes were found to bind with high affinity (delta G degree in the range of -7 to -9 Kcal/mol) to monolayers of the A431 cell line. The HA-modified liposomes were found to encapsulate EGF at high yields (% encapsulation, > 87) and to act as sustained-release depots, the rate constant for the release of the encapsulated EGF in the range of 1.4 x 10(-3) h-1. Taking all of these findings together, it is concluded that these liposomes are bioadhesive sustained-release carriers of drugs, as desired, meriting further cellular and in vivo studies.

Cell Line↗