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I Goldberg

Publications and source records attributed to I Goldberg.

At least 55 records · Page 3Linked to original sources
PubMed2001

Alphav integrin expression is a novel marker of poor prognosis in advanced-stage ovarian carcinoma.

PURPOSE: To analyze the possible correlation between expression of the alphav and beta1 integrin chains and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome. EXPERIMENTAL DESIGN: Sections from 56 primary ovarian carcinomas and metastatic lesions from 34 patients diagnosed with advanced-stage ovarian carcinoma (Fédération Internationale des Gynaecologistes et Obstetristes stages III-IV), divided into long-term (16) and short-term (18) survivors, were evaluated for expression of alphav and beta1 integrin chains using mRNA in situ hybridization. Protein expression was additionally studied in 52 specimens using immunohistochemistry. RESULTS: The mean values for disease-free survival and overall survival were 115 and 132 months for long-term survivors, as compared with 4 and 23 months for short-term survivors, respectively. Expression of alphav integrin mRNA was observed in carcinoma (18 of 56; 32%) and stromal (17 of 56; 30%) cells. beta1 integrin mRNA was similarly detected in carcinoma (25 of 56; 47%) and stromal (19 of 56; 34%) cells. No significant differences were observed when primary and metastatic lesions were compared (P > 0.05). Alphav integrin mRNA was present more often in carcinoma cells in tumors of short-term survivors (P = 0.017 for carcinoma cells). In univariate survival analysis for all cases, alphav integrin mRNA expression in tumor cells correlated with poor survival (P = 0.012). This finding retained its predictive power in a multivariate survival analysis, in which all of the molecules studied previously in this patient cohort were included (P = 0.031). Immunohistochemistry confirmed the differences in alphav integrin expression in tumor cells of short-term as compared with long-term survivors, whereas beta1 integrin protein expression was comparable in the two groups. CONCLUSIONS: To our best knowledge, this is the first evidence associating integrin expression with poor survival in ovarian carcinoma. Alphav integrin is, thus, a novel prognostic marker in advanced-stage ovarian carcinoma.

Adult↗
PubMed2000

In vivo analysis of Cajal body movement, separation, and joining in live human cells.

Cajal bodies (also known as coiled bodies) are subnuclear organelles that contain specific nuclear antigens, including splicing small nuclear ribonucleoproteins (snRNPs) and a subset of nucleolar proteins. Cajal bodies are localized in the nucleoplasm and are often found at the nucleolar periphery. We have constructed a stable HeLa cell line, HeLa(GFP-coilin), that expresses the Cajal body marker protein, p80 coilin, fused to the green fluorescent protein (GFP-coilin). The localization pattern and biochemical properties of the GFP-coilin fusion protein are identical to the endogenous p80 coilin. Time-lapse recordings on 63 nuclei of HeLa(GFP-coilin) cells showed that all Cajal bodies move within the nucleoplasm. Movements included translocations through the nucleoplasm, joining of bodies to form larger structures, and separation of smaller bodies from larger Cajal bodies. Also, we observed Cajal bodies moving to and from nucleoli. The data suggest that there may be at least two classes of Cajal bodies that differ in their size, antigen composition, and dynamic behavior. The smaller size class shows more frequent and faster rates of movement, up to 0.9 microm/min. The GFP-coilin protein is dynamically associated with Cajal bodies as shown by changes in their fluorescence intensity over time. This study reveals an unexpectedly high level of movement and interactions of nuclear bodies in human cells and suggests that these movements may be driven, at least in part, by regulated mechanisms.

Biological Transport↗
PubMed2000

Metalloporphyrin molecular sieves.

Crystal-engineering strategies have been systematically developed for the rational design by self-assembly of diverse metalloporphyrin molecular-sieve materials. Cooperative coordination and hydrogen bonding algorithms of molecular recognition proved particularly useful for this aim. The supramolecular concepts used in the construction of stable nanoporous solids and some unique sieve-type structures obtained thus far are illustrated.

Journal Article↗
PubMed2000

Dioxadiazadecalin/Salen Tautomeric Macrocycles and Complexes: Prototypal Dynamic Combinatorial Virtual Libraries New Supramolecular Host Systems, Part 12. Part 11: ref. 1. We gratefully acknowledge support by a research grant from the Israel Science Foundation and by an Intel Scholarship (to A.S.), as well as the valuable assistance of Shimon Hauptman with mass spectrometry and Yuri Paskover as an undergraduate research student.

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Journal Article↗
PubMed2000

Expression of carbohydrate antigens in advanced-stage ovarian carcinomas and their metastases-A clinicopathologic study.

OBJECTIVE: Up-regulated expression or loss of expression of various carbohydrate antigens on the surface of cancer cells has been associated with a metastatic phenotype and poor survival in epithelial malignancies of different origins. The object of this study was to investigate the expression of carbohydrate antigens in two groups of patients diagnosed with advanced-stage ovarian carcinoma-one with an extremely favorable outcome and the other with a uniformly poor survival. METHODS: Sections from 76 paraffin-embedded blocks (primary ovarian carcinomas and metastatic lesions) from 45 patients diagnosed with advanced-stage ovarian carcinomas (FIGO stages III-IV) were immunohistochemically stained using five monoclonal antibodies for Lewis(y) (Le(y))(two antibodies), Sialyl Lewis(x) (Slex), Tn, and Sialyl Tn (STn) antigens. Patients were divided in two groups based on outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Staining results for primary tumors and metastases were analyzed separately. RESULTS: Mean follow-up period was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors and 3 and 25 months for short-term survivors. Staining for all four antigens was seen in the majority of cases (range = 72-96%) and tended to be comparable in primary tumors and their metastases. However, absence of immunoreactivity for STn was seen in 9/38 (24%) metastatic lesions and only 1/38 (3%) primary tumors. This finding did not reach statistical significance (P > 0.05). A combined pattern of membranous and cytoplasmic staining was predominant in the majority of cases. Enhanced staining for Le(y) and STn was detected in the invasive front of some tumors, while Slex and Tn immunoreactivity did not relate to cell location. Primary tumors and metastatic lesions of long-term survivors displayed immunoreactivity patterns that were comparable to those of short-term survivors. In the evaluation of survival curves, more diffuse staining for Slex showed marginal correlation with poor survival (P = 0.05), while a trend toward poorer survival was seen in tumors that were more extensively stained for Le(y) and Tn (P > 0.05). CONCLUSIONS: Le(y), Slex, STn, and Tn antigens are widely expressed in primary ovarian carcinomas and their metastases. Altered expression of Sialyl Tn is observed with tumor progression in a fraction of ovarian carcinomas. Expression of membrane carbohydrate residues is prevalent in tumors of both long-term and short-term survivors and does not appear to be a strong predictor of disease outcome. However, larger studies are needed to further elucidate the role of these molecules in ovarian carcinogenesis.

Adult↗
PubMed2000

E-Cadherin complex protein expression and survival in ovarian carcinoma.

OBJECTIVE: The aim of this study was to analyze the correlation between expression of E-cadherin complex proteins, epidermal growth factor receptor (EGFR), and c-erbB-2 and disease outcome in advanced-stage ovarian carcinomas. METHODS: Sections from 75 primary ovarian carcinomas (=37) and metastatic lesions (=38) from 45 patients diagnosed with advanced-stage ovarian carcinoma (FIGO stage III-IV) were immunostained and evaluated for staining pattern, extent, and intensity. Patients were divided in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cutoff of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. RESULTS: Comparison of all primary and metastatic lesions showed upregulation of gamma-catenin protein expression in the latter (P = 0.05). When segregated according to disease outcome, the expression of all studied proteins, with the exception of EGFR, was more diffuse in tumors of short-term survivors. The presence of cytoplasmic staining for c-erbB-2 was associated with poor survival in the entire cohort (P = 0.007), as well as in primary tumors alone (P = 0.003), in survival analysis. Similar results were seen in the evaluation of primary tumors for gamma-catenin (P = 0.002). CONCLUSIONS: gamma-Catenin, and possibly c-erbB-2, are valid markers of poor survival in advanced-stage ovarian carcinoma.

Adult↗
PubMed2000

Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis.

Heat shock proteins are a family of approximately 25 highly conserved proteins upregulated in response to various forms of stress. They play an active role in the development autoimmune diseases in animals, and have been incriminated in human autoimmune diseases (i.e. rheumatoid arthritis, multiple sclerosis). It has been previously shown, that an induced immune response against Heat shock protein 65 (HSP-65) results in atherosclerotic lesions in normocholesterolemic rabbits. We have supported these findings showing that C57BL/6 mice immunized with HSP-65 and fed a high-fat diet develop enhanced fatty streaks. To create a model that will eliminate the need for exogenous supplementation of a high-fat diet, we have immunized LDL receptor deficient (LDL-RD) mice with HSP-65 or with heat-killed Mycobacterium tuberculosis (Mt). Seven groups of LDL-RD mice (n=10), were immunized subcutaneously with different concentrations of HSP-65, Mt or bovine serum albumin (BSA). All mice were fed a normal chow-diet for 3 months. The mice immunized with the higher doses of Mt developed significantly larger fatty streaks when compared with their BSA immunized littermates. The size of the lesions in the aortic sinus were: 31,562+/-5,994 microm(2)in the 10 microg Mt and 52,777+/-5,245 microm(2)in the 100 microg Mt vs. 11, 500+/-3,750 microm(2)in the BSA group (P<0.05). In the HSP-65-immunized mice, only the group injected with the highest dose (5 microg, twice) developed significantly larger fatty streaks when compared with the BSA-immunized group (28,611+/-4,716 microm(2)vs. 11,500+/-3,750 microm(2)respectively, (P<0.05). The HSP-65-but not the Mt- or BSA-immunized mice developed high titers of anti HSP-65 antibodies, beginning 10 days after the immunization, which persisted until they were killed. Immunohistochemical staining showed CD3-positive lymphocytes in the aortic sinus of mice immunized with Mt or HSP-65, but not in the control group. Thus, we established a mouse model of HSP-65 immune mediated atherosclerosis devoid of high fat diet supplementation. This model will enable us to further study the role of the immune system in atherosclerosis, via HSP-65 and raise novel immunomodulatory therapeutic modalities.

Animals↗
PubMed2000

Immunohistochemical analyses of sporadic and familial (185delAG carriers) ovarian cancer in Israel.

A single germ line mutation in BRCA1, (185delAG) is detected in a substantial portion of Jewish Israeli patients with ovarian cancer. Whether disease phenotypes differ in BRCA1 mutation carriers and sporadic cases is presently a subject for debate. To gain insight into this issue, we analysed tumours from 65 Jewish women with ovarian cancer, 29 (45%) were 185delAG BRCA1 mutation carriers, and 36 (55%) were non-carriers of any of the predominant Jewish mutations in BRCA1 or BRCA2 (sporadic). In 19/29 mutation carriers (66%) diagnosis was made prior to age 60 years, compared with 14/36 (39%) of the non-carriers (P=0.03; Yates corrected P=0.06). Low malignant potential ('borderline') tumours were detected less frequently among carriers (2/29; 7%) than non-carriers (9/36; 25%) (P=0.03; one tail P=0.05). Immunohistochemical analysis in invasive carcinoma (n=54) showed that 17/27 carriers (63%) and 18/27 non-carriers (67%) had positive nuclear staining with a p53 antibody. In 4/27 carriers (15%) and 3/25 non-carriers (12%), 25% or more of the tumour cells stained positive for Ki-67, an insignificant difference. Results were not altered by including borderline tumours (n=11) in these analyses. We conclude that the rate of TP53 inactivation and proliferative index in ovarian cancer, are similar for 185delAG BRCA1 mutation carriers and sporadic cases.

Aged↗
PubMed2000

Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16.

The papillomavirus major late protein, L1, forms the pentameric assembly unit of the viral shell. Recombinant HPV16 L1 pentamers assemble in vitro into capsid-like structures, and truncation of ten N-terminal residues leads to a homogeneous preparation of 12-pentamer, icosahedral particles. X-ray crystallographic analysis of these particles at 3.5 A resolution shows that L1 closely resembles VP1 from polyomaviruses. Surface loops contain the sites of sequence variation among HPV types and the locations of dominant neutralizing epitopes. The ease with which small virus-like particles may be obtained from L1 expressed in E. coli makes them attractive candidate components of a papillomavirus vaccine. Their crystal structure also provides a starting point for future vaccine design.

Amino Acid Sequence↗
PubMed2000

Expression of angiogenesis-related genes in ovarian carcinoma--a clinicopathologic study.

Angiogenic factors play a role in tumor growth and spread. The object of this study was to analyze the correlation between mRNA expression of angiogenesis-related genes and disease outcome in advanced-stage ovarian carcinomas. Sections from 66 primary ovarian carcinomas and metastatic lesions from 41 patients diagnosed with advanced stage ovarian carcinoma (FIGO stages III-IV) were evaluated for expression of basic fibroblast factor (bFGF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) using mRNA In Situ Hybridization (ISH). Patients were divided in two groups based on disease outcome. Long-term survivors (17 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period was 70 months. The mean values for DFS and OS were 116 and 133 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Expression of bFGF mRNA, most often intense, was detected in tumor and stromal cells in the majority of cases. Weak expression of IL-8 mRNA was detected in both cell compartments, while VEGF mRNA expression was limited to few cases. Primary tumors displayed higher bFGF and IL-8 mRNA expression. However, these differences did not reach statistical significance (P > 0.05). bFGF, IL-8 and VEGF mRNA expression in both tumor and stromal cells was comparable in tumors of long-term and short-term survivors, and showed no correlation with disease outcome in survival analysis (P > 0.05). bFGF is the major angiogenic factor expressed in ovarian carcinoma at the mRNA level. mRNA expression of VEGF, bFGF, and IL-8 does not appear to be a predictor of disease outcome in advanced-stage ovarian carcinoma.

Adult↗
PubMed2000

Expression of topoisomerase II and Ki-67 in cervical carcinoma--clinicopathological study using immunohistochemistry.

AIM: To study the correlation between the expression of topoisomerase II and Ki-67 antigen and disease outcome in cervical squamous cell carcinomas. EXPERIMENTAL DESIGN: Forty-nine cervical carcinomas, 10 cases of high-grade cervical intraepithelial neoplasia (CIN II-III) and 5 control cervices were stained by monoclonal antibodies for topoisomerase II and Ki-67 (MIB-1 clone). Nuclear counts were correlated with patient age, tumor stage, histological grade and survival. RESULTS: Thirteen patients died of disease, 35 remained free of disease, and one patient was lost to follow up. Ki-67 counts were higher in CIN lesions, when compared to both invasive carcinomas and control cervices. Topoisomerase II counts were comparable for CIN and invasive tumors. No immunoreactivity for topoisomerase was detected in control cases. Neither stage nor grade was associated with nuclear counts using either marker. In multivariate survival analysis, stage (p=0.001), grade (p=0.03) and older patient age (p=0.02) predicted poor survival. Ki-67 counts predicted survival with borderline significance (p=0.07), while topoisomerase II counts were not related to survival. CONCLUSION: Ki-67 and topoisomerase II counts do not appear to have a significant role in the prediction of survival in cervical squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed2000

Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia.

Insulin gene expression is restricted to islet beta cells of the mammalian pancreas through specific control mechanisms mediated in part by specific transcription factors. The protein encoded by the pancreatic and duodenal homeobox gene 1 (PDX-1) is central in regulating pancreatic development and islet cell function. PDX-1 regulates insulin gene expression and is involved in islet cell-specific expression of various genes. Involvement of PDX-1 in islet-cell differentiation and function has been demonstrated mainly by 'loss-of-function' studies. We used a 'gain-of-function' approach to test whether PDX-1 could endow a non-islet tissue with pancreatic beta-cell characteristics in vivo. Recombinant-adenovirus-mediated gene transfer of PDX-1 to the livers of BALB/C and C57BL/6 mice activated expression of the endogenous, otherwise silent, genes for mouse insulin 1 and 2 and prohormone convertase 1/3 (PC 1/3). Expression of PDX-1 resulted in a substantial increase in hepatic immunoreactive insulin content and an increase of 300% in plasma immunoreactive insulin levels, compared with that in mice treated with control adenovirus. Hepatic immunoreactive insulin induced by PDX-1 was processed to mature mouse insulin 1 and 2 and was biologically active; it ameliorated hyperglycemia in diabetic mice treated with streptozotocin. These data indicate the capacity of PDX-1 to reprogram extrapancreatic tissue towards a beta-cell phenotype, may provide a valuable approach for generating 'self' surrogate beta cells, suitable for replacing impaired islet-cell function in diabetics.

Adenoviridae↗
PubMed2000

High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-kappaB activation.

Based on the essential involvement of NF-kappaB in immune and inflammatory responses and its apoptosis-rescue function in normal and malignant cells, inhibitors of this transcription factor are potential therapeutics for the treatment of a wide range of diseases, from bronchial asthma to cancer. Yet, given the essential function of NF-kappaB in the embryonic liver, it is important to determine its necessity in the liver beyond embryogenesis. NF-kappaB is normally retained in the cytoplasm by its inhibitor IkappaB, which is eliminated upon cell stimulation through phosphorylation-dependent ubiquitin degradation. Here, we directed a degradation-resistant IkappaBalpha transgene to mouse hepatocytes in an inducible manner and showed substantial tissue specificity using various means, including a new method for live-animal imaging. Transgene expression resulted in obstruction of NF-kappaB activation, yet produced no signs of liver dysfunction, even when implemented over 15 months. However, the transgene-expressing mice were very vulnerable both to a severe immune challenge and to a systemic bacterial infection. Despite having intact immunocytes and inflammatory cells, these mice were unable to clear Listeria monocytogenes from the liver and succumbed to sepsis. These findings indicate the essential function of the hepatocyte through NF-kappaB activation in certain systemic infections, possibly by coordinating innate immunity in the liver.

Animals↗
PubMed2000

Cellular localization of complement C3 and C4 transcripts in intestinal specimens from patients with Crohn's disease.

It has been suggested that the increase in C3 and C4 levels in jejunal perfusates of patients with Crohn's disease (CD) results from local intestinal synthesis of complement. The present study evaluated the expression of these complement genes in inflamed tissues from patients with CD. Surgically resected specimens from patients with CD and control tissue obtained from subjects with adenocarcinoma of the colon were evaluated for C3 and C4 gene expression by the use of 35S-labelled anti-sense RNA probes. All tissue samples, diseased and normal tissue, expressed C4 mRNA throughout in the intestinal epithelium. C3 mRNA was not detected in epithelial cells in histologically normal tissue, but in diseased specimens there was a focal distribution of C3 mRNA in epithelial cells of the crypts, but not in villous epithelium. Focal C3 gene expression correlated with crypt abscess formation and the presence of polymorphonuclear leucocytes in the lumen of the crypts. In addition, C3 mRNA was also found in macrophages of the submucosa. These macrophages were CD68+, fusiform with faint cytoplasm and morphologically different from the large rounded lamina propria macrophages, which do not express C3 mRNA. Multinucleated giant cells did not express either C3 or C4 genes. In addition to its presence in intestinal epithelium, C4 mRNA was also expressed in mast cells, which however did not express C3 mRNA. These observations identify cells in the intestinal wall expressing complement genes and support the hypothesis that there is local regulated production of complement in the intestine of patients with CD, and subsequent complement activation may contribute to the inflammatory process.

Adrenal Cortex Hormones↗
PubMed2000

A comparison of short wavelength automated perimetry with frequency doubling perimetry for the early detection of visual field loss in ocular hypertension.

BACKGROUND: Achromatic automated perimetry (AAP) is limited in its ability to detect very early visual field loss in ocular hypertensive patients. Tests targeting axons that are selectively damaged, or have low redundancy, may detect visual field losses before they are seen on AAP. It has been claimed that short wavelength automated perimetry (SWAP) and frequency doubling perimetry (FDP) are two tests that provide early detection. METHODS: Patients (n = 62) were selected on the basis that they had raised intraocular pressure but normal visual fields detected by AAP. A SWAP and an FDP was performed on each of the patients and the results compared. Fields were scored as either normal or abnormal based on criteria used in previous studies. RESULTS: On comparing FDP with SWAP as the 'gold standard', a sensitivity of 88.9% and a specificity of 96.2% was found, showing a high concordance between the two tests. CONCLUSION: These results suggest that as SWAP may be predictive of AAP visual field loss, FDP may be similarly predictive.

Adult↗