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Biomedical subjects

I Levin

Publications and source records attributed to I Levin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Crystallographic studies on the ribosome, a large macromolecular assembly exhibiting severe nonisomorphism, extreme beam sensitivity and no internal symmetry.

Crystals, diffracting best to around 3 A, have been grown from intact large and small ribosomal subunits. The bright synchrotron radiation necessary for the collection of the higher-resolution X-ray diffraction data introduces significant decay even at cryo temperatures. Nevertheless, owing to the reasonable isomorphism of the recently improved crystals of the small ribosomal subunits, reliable phases have been extracted at medium resolution (5-6 A) and an interpretable five-derivative MIR map has been constructed. For the crystals of the large subunits, however, the situation is more complicated because at higher resolution (2.7-7 A) they suffer from substantial radiation sensitivity, a low level of isomorphism, instability of the longest unit-cell axis and nonisotropic mosaicity. The 8 A MIR map, constructed to gain insight into this unusual system, may provide feasible reasoning for the odd combination of the properties of these crystals as well as hints for future improvement. Parallel efforts, in which electron-microscopy-reconstructed images are being exploited for molecular-replacement studies, are also discussed.

Animals↗
PubMed1998

Identification of a cytoplasmic motif in the erythropoietin receptor required for receptor internalization.

Erythropoietin (EPO) promotes the viability, proliferation and differentiation of mammalian erythroid progenitor cells via its specific cell surface receptor. The EPO receptor (EPO-R) is a member of the cytokine receptor superfamily and is comprised of one identified subunit which homodimerizes upon ligand binding. To study the role of the intracellular domain of the EPO-R in the endocytosis of EPO, we compared the rate and extent of 125I-EPO endocytosis by wild type (wt) EPO-R and five cytoplasmically truncated EPO-Rs: 1-251 EPO-R, 1-257 EPO-R, 1-267 EPO-R, 1-276 EPO-R and 1-306 EPO-R which contain 4, 10, 20, 29 or 59 amino acids of the cytoplasmic domain, respectively. We also studied an EPO-R mutant (PB) which lacks amino acid residues 281-300 of the cytoplasmic domain. The experiments were conducted in COS 7 cells transfected with the EPO-R cDNAs and in Ba/F3 cells stably expressing the wt EPO-R, 1-251 or 1-257 EPO-R. Cells expressing wt EPO-R, PB EPO-R (delta281-300), 1-276 EPO-R or 1-306 EPO-R internalized approximately 50% of 125I-EPO bound to the cell surface, while cells expressing 1-251, 1-257 or 1-267 EPO-R internalized only 25% of the bound 125I-EPO. The steady-state expression levels of these latter receptors on the cell surface were typically 2-5-fold higher than wt EPO-R. Our data indicate that amino acid residues 267-276 (FEGLFTTHK) of the EPO-R cytoplasmic domain may have a role in receptor internalization. Metabolic labeling experiments suggest that in transiently transfected COS 7 cells most of the wt EPO-R and 1-257 EPO-Rs do not exit the ER and may be degraded there. The half-life of both receptors was essentially similar and was in the range of 1 h. In Ba/F3 cells the mature Golgi processed 1-257 EPO-R was more stable than the corresponding form of the wt EPO-R, possibly contributing to its higher cell surface expression.

Amino Acid Sequence↗
PubMed1997

A comparison of the geometric reasoning of students attending Israeli ultraorthodox and mainstream schools.

Effects of schooling on a geometric misconception were examined by comparing the performance of Israeli students attending ultraorthodox schools with that of peers attending mainstream schools. These groups were of special interest because both value education highly and send essentially all children to school, but I group receives extensive instruction in mathematics and science and the other receives almost none. Despite the ultraorthodox 12- to 14-year-olds' having received no instruction in geometry, they more often solved the geometric misconception problems than did mainstream peers who had received extensive instruction in the subject. Mainstream 16- to 18-year-olds did somewhat better on the misconception task than did orthodox age peers, but even there, the advantage of the mainstream students was limited to those exposed to the most advanced mathematics curriculum. How mainstream and orthodox schooling may have contributed to these findings is discussed.

Achievement↗
PubMed1996

Correlation between tumour and serum beta 2m expression in patients with breast cancer.

HLA class I antigens are composed of a major histocompatibility complex (MHC) encoded heavy chain that is associated non-covalently with a light chain beta-2 microglobulin (beta-2m). When the HLA complex is metabolized, beta-2m is shed into the serum. A large variety of human and experimental tumours have altered MHC class I expression. In a previous study we observed elevated mean beta-2m serum levels in breast cancer patients, as compared to controls. To study the relationship between tumour expression and serum levels, we examined 54 patients with breast cancer. Tumour beta-2m was determined by immunohistochemistry and serum levels by the ELISA technique. Of the 54 patients, 38 had low and 16 had high beta-2m expression on the tumour. There was a significant correlation between tumour beta-2m and serum beta-2m levels (P = 0.02), with patients whose tumours expressed high beta-2m having high serum beta-2m levels. There was an inverse correlation between tumour grade and tumour beta-2m expression which approached statistical significance (P = 0.06). These findings suggest that in a substantial number of patients the high serum levels derive from shedding of beta-2m from tumour cells. These levels may have implications for tumour growth and metastases due to influences on immunological responses.

Adult↗
PubMed1996

HLA class I antigen expression in human solid tumors.

The expression of HLA class I antigens was studied by immunohistochemistry in various tumors in correlation with clinicopathologic characteristics. Reduced expression was observed in germ cell testicular cancer, kidney, prostate, gastric and colon cancer, and was associated with tumor aggressiveness, grade and penetration of the tumor through the organ wall. In bladder cancer reduced expression was associated with poor survival. Irradiation of brain tumors resulted in an increase in class I expression. Soluble class I levels were studied in breast and colon cancer patients and were found to be high in those with metastatic disease. The clinical relevance of reduced class I levels are discussed.

Gene Expression Regulation, Neoplastic↗
PubMed1995

Development of a genetic map of the chicken with markers of high utility.

Microsatellites are tandem duplications with a simple motif of one to six bases as the repeat unit. Microsatellites provide an excellent opportunity for developing genetic markers of high utility because the number of repeats is highly polymorphic, and the assay to score microsatellite polymorphisms is quick and reliable because the procedure is based on the polymerase chain reaction (PCR). We have identified 404 microsatellite-containing clones of which 219 were suitable as microsatellite markers. Primers for 151 of these microsatellites were developed and used to detect polymorphisms in DNA samples extracted from the parents of two reference populations and three resource populations. Sixty, 39, 46, 49, and 61% of the microsatellites exhibited length polymorphisms in the East Lansing reference population, the Compton reference population, resource population No. 1 (developed to identify resistance genes to Marek's disease), resource population No. 2 (developed to identify genes involved in abdominal fat), and resource population No. 3 (developed to identify genes involved in production traits), respectively. The 91 microsatellites that were polymorphic in the East Lansing reference population were genotyped and 86 genetic markers were eventually mapped. In addition, 11 new random amplified polymorphic DNA (RAPD) markers and 24 new markers based on the chicken CR1 element were mapped. The addition of these markers increases the total number of markers on the East Lansing genetic map to 273, of which 243 markers are resolved into 32 linkage groups. The map coverage within linkage groups is 1,402 cM with an average spacing of 6.7 cM between loci. The utility of the genetic map is greatly enhanced by adding 86 microsatellite markers. Based on our current map, approximately 2,550 cM of the chicken genome is within 20 cM of at least one microsatellite marker.

Animals↗
PubMed1995

The significance of soluble interleukin-2, soluble interleukin-2 receptors, soluble ICAM-1 and beta 2-microglobulin in breast cancer patients.

The serum levels of soluble interleukin-2 (sIL-2), sIL-2 receptors (sIL-2R), beta 2-microglobulin (beta 2M) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by the ELISA technique in 129 breast cancer patients and 40 controls. The median serum levels of sIL2-R, beta 2M and sICAM-1 were significantly higher and sIL-2 significantly lower than controls. sIL-2R, sICAM-1 and beta 2M levels were significantly higher in patients with metastatic disease compared to patients on long-term follow-up with no active disease. Initial study measurements of these markers could not identify patients at high risk for relapse. These findings suggest that the sIL-2R level is indicative of metastatic disease and together with other parameters of immune activation may be of help in monitoring disease activity in breast cancer patients.

Adult↗
PubMed1994

The effect of irradiation on expression of HLA class I antigens in human brain tumors in culture.

The immunosuppressive effects of irradiation are well known; however, under certain circumstances irradiation also augments the local immune response by as yet undefined mechanisms. Because of the importance of HLA class I antigen in immune regulation and the fact that killing of tumor cells by cytotoxic T cells is HLA antigen-restricted, the authors studied HLA class I antigen expression in eight glioblastomas multiforme, four meningiomas, and four medulloblastomas. Twenty fragments of each tumor specimen were placed in short-term cultures immediately after resection. For each tumor, control Sample 1 was not irradiated. Sample 2 was irradiated on Day 1, and two groups of the remaining pieces of each tumor (specimens 3 to 10) were irradiated on two consecutive days. Escalating radiation doses were given, starting at 200 cGy/day for Sample 2 up to 1000 cGy/day for Sample 10. The total dose range was 200 to 2000 cGy. Corresponding nonirradiated tumor fragments served as controls. Four hours after irradiation, each sample was processed and stained for HLA class I antigen using the immunoperoxidase technique. The tumor cells were intensely stained in nonirradiated glioblastomas and meningiomas, whereas no staining was observed in medulloblastomas. In four of the eight glioblastomas and in all four meningiomas, irradiation augmented HLA class I antigen expression compared to controls. This effect was dose-dependent and was maximum in the 1200 cGy-treated specimens. No change was observed in the other four glioblastomas or in the medulloblastomas. The data suggest that irradiation does not decrease and may even induce HLA class I antigen expression in some brain tumors. This may be one of the mechanisms by which immunotherapy operates after irradiation. Further studies are required to elucidate optimum radiation doses and fractionation as well as optimum timing of immunotherapy.

Brain Neoplasms↗
PubMed1994

The expression of HLA class I antigen in prostate cancer in relation to tumor differentiation and patient survival.

The expression of HLA class I antigens was studied using the immunoperoxidase technique on 30 patients with prostate cancer and 29 patients with benign prostatic hypertrophy (BPH). Forty-three percent of the tumors stained positive, in contrast to 21% of the BPH. An inverse relationship was noted between class I expression and degree of tumor differentiation: 88% of the well-differentiated tumors (8/9) expressed class I antigen, compared with 33% (3/9) of the moderately differentiated and 16% (2/12) of the poorly differentiated tumors. No significant survival difference was found between those with class I-positive and -negative tumors. However, when both class I expression and degree of differentiation were considered, those with positive tumors at each level of differentiation had better survival than those with negative tumors. These data suggest that HLA class I expression may serve as a finite prognostic factor and may have relevance in future immunotherapy.

Adenocarcinoma↗
PubMed1993

Genetic map of the chicken Z chromosome using random amplified polymorphic DNA (RAPD) markers.

Commercially important traits of domestic animals have often been genetically linked to sex chromosomes, such as the Z chromosome of chickens. Using a backcross mapping population between two divergent, inbred lines and random-amplified polymorphic DNA (RAPD)-PCR markers, a genetic map of the chicken Z chromosome has been generated. Thirteen Z-linked RAPD markers were identified, mapped, and linked to two RFLPs and one phenotypic marker. The protocol used also generated RAPD markers for the W chromosome. The linkage distances obtained suggest that the RAPD markers are widely distributed throughout the Z chromosome and are likely to be linked to most or all traits of interest on this chromosome. The map provides a preliminary estimate of genetic to physical distance of about 0.5 Mb per centimorgan for the Z chromosome in chickens (male-specific recombination). A similar approach should be applicable to facilitate the mapping and analysis of sex-linked traits in other domestic animals.

Animals↗
PubMed1991

Expression of class I histocompatibility antigens in transitional cell carcinoma of the urinary bladder in relation to survival.

The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning.

Adult↗
PubMed1991

Cellular B-2 microglobulin expression as a prognostic indicator in renal cell carcinoma.

The expression of B-2 microglobulin (B-2M) on tumor cells and their normal cell counterparts in 39 patients with renal cell carcinoma was studied and correlated to tumor stage and survival. The median survival time of patients with localized disease (stage I) whose tumors expressed B-2M was 10.2 years while the median survival time for patients whose tumors did not express B-2M was only 3.6 years (p less than 0.001). For patients with more advanced disease (stages II, III, IV) whose tumors expressed B-2M, median survival time was 3.6 years compared to 2.0 years in patients whose tumors did not express B-2M, a non-significant difference. It is suggested that the tumor cell membrane expression of B-2M may serve as an indicator of good prognosis in early renal cell carcinoma.

Adolescent↗
PubMed1991

The influence of ev6 on the immune response to avian leukosis virus infection in rapid-feathering progeny of slow- and rapid-feathering dams.

Endogenous virus (EV) locus ev6 encodes only virus envelope glycoprotein. The influence of ev6 on the immune response to contact infection with hatchmates infected with avian leukosis virus (ALV) was compared in replicate hatches. The ALV Subgroup E-resistant, rapid-feathering (RF) female chickens produced by slow-feathering (SF) and RF dams with and without ev6 were exposed at hatch to hatchmates infected with ALV Subgroup A (Strain RPL-40). The RPL-40 viremia, shedding, and virus neutralizing antibodies were measured among pullets from two hatches at 22 wk of age. Although significant (P less than .05) differences between hatches in the immune response to contact infection were noted among ev6+ pullets, significantly fewer ev6+ pullets seroconverted than their ev6- hatchmates. At 22 wk of age, significantly more lymphomas were also found among ev6+ pullets than among ev6- hatchmates. In flocks wherein both parents and progeny were homozygous resistant to Subgroup E virus, there was no deterimental maternal effect on RF progeny from SF dams that carried ev21. These results also confirm that selection for genetic cellular resistance to Subgroup E ALV infection eliminates congenital transmission of EV21.

Animals↗
PubMed1991

Association of a chicken repetitive element with the endogenous virus-21 slow-feathering locus.

The DNA sequences of an endogenous virus ev21-cell junction fragment (JFIL-1), and the pristine ev21 unoccupied region were analyzed. Comparisons of 3' proviral sequences of JFIL-1 with comparable regions of ev2, the prototype Rous-associated provirus (RAV-0), revealed minor single-base substitutions in the transmembrane domain of proviral envelope glycoprotein and the long terminal repeat of ev21. In the cell component of the JFIL-1, insertion of a 9-bp direct repeat and deletion of a guanine deoxynucleotide abolished HaeIII and BalI recognition sites that were present in the pristine region. Upstream from the insertion site, a large region was 71 and 75% homologous with dispersed chicken repetitive (CR1) elements associated with vitellogenin and very low density apolipoprotein II genes, respectively. Southern blot hybridizations and comparisons of CR1 motifs such as polypurine tracts, a tandem imperfect octamer, and 6-bp duplications indicated that this sex-linked, CR1 element (CR1ev21) may be the longest member of this family reported thus far.

Animals↗
PubMed1991

Application of a locus-specific DNA hybridization probe in the analysis of the slow-feathering endogenous virus complex of chickens.

To investigate further the sex-linked, slow-feathering (SF) locus, a DNA hybridization probe that flanks the integration site of endogenous virus ev21 was used to probe Southern blots from a variety of commercial SF White Leghorn (WL), broiler, and endangered lines. After HaeIII digestion of DNA from SF WL, the 5' and 3' provirus-cell junction fragments were seen in addition to a 2.5-kb fragment of cell sequences that was homologous with the viral integration region. The latter polymorphism, which appeared to represent sequences duplicated after integration of EV21, was designated unoccupied repeat URa. Among SF broiler crosses, the same provirus-cell junction fragments were found but the pristine region that represented the 1.6-kb proviral URb was also found. Only URb was found among rapid-feathering (RF) chickens, regardless of breed. Although there was marked (greater than 95%), agreement between the presence of ev21-cell; junction fragments and the SF phenotype among both WL and broilers, Southern blots of DNA from a few commercial SF broiler chickens lacked ev21 junction fragments but some RF revertants harbored ev21 junction fragments. These anomalies suggest that ev21 may not be the sole determinant of the SF phenotype.

Animals↗