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Biomedical subjects

G Selzer

Publications and source records attributed to G Selzer.

At least 19 recordsLinked to original sources
PubMed1989

Production and characterization of monoclonal antibodies identifying breast tumor-associated antigens.

We have generated a mouse monoclonal antibody (H23) against the retrovirus-like particles (human mammary tumor virus) released in vitro by the human breast adenocarcinoma cell line T47D. This antibody reacts specifically with a glycoprotein with an apparent molecular mass of 68 kDa (gp68) that is detected in the growth medium of T47D cells as well as in pleural effusion fluids from breast adenocarcinoma patients. No detectable levels of this antigen could be observed in pleural effusions of patients with cancers other than of breast origin. The H23-related antigen was localized in the cytoplasm of breast tumor cells as well as on the cell surface of both T47D cells and metastatic cells from breast cancer patients. A survey of tissue from 812 patients was performed by using H23 in an indirect immunoperoxidase assay. The results showed that the antigen was detectable in 91% of all breast tumors tested. No cytoplasmic staining was observed in either normal tissues or nonbreast carcinomas. Only one of the benign breast tissues tested (out of a total of 56 samples of tissue) was positive for this antigen. Given the ability of this antibody to specifically detect breast tumor cells, H23 may be of importance in diagnosis and in clinical follow-up of patients for the detection of metastatic lesions by imaging and for therapy.

Adenocarcinoma↗
PubMed1989

Coronary stenosis dilation by low dose intravenous nitroglycerin.

In a randomized double-blind study, 40 patients with coronary heart disease received either 0.025 mg nitroglycerin or placebo intravenously. Before and 2-3 min after injection, the aortic and left ventricular pressures were recorded and coronary angiography was performed. Mean heart rate, systolic and diastolic aortic pressure, left ventricular filling pressure and the pre- and poststenotic coronary artery diameters, as well as the diameters of representative distal coronary artery segments showed no significant changes. Coronary artery stenosis diameters remained unchanged after placebo (1.01 +/- 0.5 to 1.13 +/- 0.49 mm; n.s.) but increased significantly after nitroglycerin from 1.15 +/- 0.68 to 1.32 +/- 0.73 mm (P less than 0.01). Since it has been demonstrated, on the other hand, that the same dose of nitroglycerin reveals antianginal activity, it can be hypothesized from these results that dilatation of coronary stenoses plays an important role in the antianginal action of nitroglycerin. Strong haemodynamic effects do not appear to be a prerequisite of the beneficial effects of nitroglycerin.

Adult↗
PubMed1987

Increased expression in Escherichia coli of a synthetic gene encoding human somatomedin C after gene duplication and fusion.

A synthetic gene coding for human somatomedin C (SMC) was inserted into an Escherichia coli plasmid vector that contains the bacteriophage lambda pL promoter. Intracellular accumulation of the gene product after induction of the promoter was found to be low. A 200-fold greater yield was obtained with a similar plasmid containing two translationally fused copies of the SMC gene. A series of such tandem genes truncated at their 3' ends were generated with nuclease Bal 31. These gave intermediate expression levels that correlated with the expected sizes of their gene products. Comparison of RNAs extracted from cells containing either the monomer or tandem SMC gene constructions showed that there was no significant difference in expression at the transcriptional level. Pulse-chase experiments demonstrated that the tandem SMC protein was far more stable than the monomer SMC product.

Amino Acid Sequence↗
PubMed1987

Prognostic factors in breast cancer--a pathological and immunological study of patients with stage 1 breast cancer.

In order to analyze which features determine a poorer prognosis we undertook a study of 91 consecutive patients with pathological Stage I breast cancer operated on at Beth Israel Medical Center (1968-71). Tumor tissue slides were reviewed and features such as: tumor size, histologic type, nuclear grade, lymphocytic and perivenular lymphocytic infiltration, as well as sinus histiocytosis in the lymph nodes removed. Records were reviewed and classified according to age and ethnic background. Survival and recurrence data were recorded up to 14 years post-mastectomy. Also determined was the presence of an antigen, previously detected in certain human breast cancer tumor tissues, which has been found to cross-react immunologically with the 52,000 dalton major envelope protein of the mouse mammary tumor virus (MMTV--gp52). Ten-year cumulative disease-free survival was 0.65. Univariate analysis of survival within various factors revealed that the only statistically significant influencing factor was the presence or absence of the antigen. Factors such as perivenous lymphocytic infiltration, diffuse lymphoid infiltration and sinus histiocytosis in regional lymph nodes also showed trends in favor of improved survival but the sample may be too small for statistical significance. The presence or absence of the antigen was independent of the host immunological reaction. There was no relationship between localization of tumor, whether medial or lateral and survival, nor with presence or absence of antigen.

Antigens, Neoplasm↗
PubMed1987

[Coronary-dilating effect of minimal doses of nitroglycerin].

A previous study verified the antianginal efficacy of 0.025 mg nitroglycerin without it having any effect on heart rate and blood pressure. In a randomized double-blind study, 40 patients with coronary heart disease received intravenously either 0.025 mg nitroglycerin or placebo. Before and 1-2 min after injection, the aortic and left ventricular (n = 20) pressures were recorded and coronary angiography performed. Mean heart rate, systolic and diastolic aortic pressure, left ventricular filling pressure and the pre- and poststenotic diameter of the coronary arteries, as well as the diameter of a distal coronary artery segment, showed no significant changes (p greater than 0.05). The stenotic segment diameter of the coronary artery remained unchanged after placebo administration (1.01 +/- 0.5 to 1.13 +/- 0.49 mm; p greater than 0.05) but increased significantly after the injection of nitroglycerin (from 1.15 +/- 0.68 to 1.32 +/- 0.73 mm; p less than 0.01). These results support the hypothesis that dilatation of coronary stenoses is an important aspect of the antianginal action of nitroglycerin. This may have practical consequences in the treatment of patients with angina and low blood pressure or severe headaches after the administration of conventional doses of nitroglycerin.

Angina Pectoris↗
PubMed1986

Immunohistochemistry of primary gastrointestinal lymphomas: a study of 76 cases.

A retrospective study of 76 primary gastrointestinal lymphomas utilizing an avidin: biotinylated horseradish peroxidase complex (ABC) technique demonstrated 22 B-cell lymphomas, including two associated with alpha-heavy chain disease. Seven cases were classified as true histiocytic lymphomas based on a positive reaction for one or more of three histiocytic enzyme markers utilized, predominantly alpha-1-antitrypsin and alpha-1-antichymotrypsin. However, in 20 cases, an intense admixture of reactive histiocytes was noted and these cells stained preferentially for the enzyme, lysozyme. Twenty cases, which stained for both kappa and lambda light chains and positively or negatively for albumin, could not be classified and 27 cases failed to stain with any of the antisera utilized.

Antibodies↗
PubMed1986

Mapping 5' termini of JC virus early RNAs.

Within its enhancer promoter region, the MAD-1 strain of JC virus (JCV) has two 98-base-pair tandem repeats, each containing a TATA box-like sequence. In the present study, polyadenylated early JCV mRNAs were isolated 5 or 29 days after infection of primary human fetal glial (PHFG) cells. By using S1 nuclease, the 5' termini of the early mRNAs were mapped to nucleotide position(s) (np) 122 through 125, which lies within an AT rich region (at np 113 through 127). In contrast, when JCV DNA was transcribed in vitro, we observed a single major cluster of 5' start sites at np 94 through 97, which is approximately 25 base pairs downstream from one of the TATA boxes. By day 5, the earliest time at which JCV RNA was detected, viral DNA replication had begun; it continued for at least an additional 20 days. Since more late than early RNA was present at 5 days postinfection, the early RNAs whose synthesis began at np 122 through 125 may be analogous to SV40 late early mRNA (Ghosh and Lebowitz, J. Virol. 40:224-240, 1981). However, we have not detected RNAs with 5' termini 25 to 30 bp downstream from the TATA box at earlier times. While JCV contains two identical TATA boxes, one in each of the 98-bp repeats, only the upstream TATA box functions as an early promoter element.

Cell Line↗
PubMed1985

Optimizing the expression in E. coli of a synthetic gene encoding somatomedin-C (IGF-I).

Double-stranded DNA encoding the human hormone somatomedin-C (SMC) has been synthesized. This synthetic gene has been inserted into a plasmid bearing the strong leftward promoter (PL) of bacteriophage lambda and expressed in E. coli. Codons for the N-terminal region of SMC which maximized the hormone's synthesis were chosen in an SMC-lac z fusion assay. The amounts of SMC accumulated in E. coli were influenced by mutations at two chromosomal loci, lon and htpR.

ATP-Dependent Proteases↗
PubMed1984

Transformation of chronic lymphocytic leukemia to plasmacytoma.

In a woman with chronic lymphocytic leukemia (CLL), a maxillary plasmacytoma developed after 8 years. The membrane-bound immunoglobulin of the leukemic lymphocytes, the cytoplasmic immunoglobulin of the plasma cells, the serum monoclonal protein and the urine Bence-Jones protein had the same heavy and light chains--mu kappa. This suggests that the leukemic cells transformed to plasma cells. This very rare event is a complete reversal of the more common transformation that occurs in CLL and manifested by de-differentiation. Only in one case out of the 20 previously reported patients with CLL and multiple myeloma there was evidence, like in the current case, of a common clonal origin of the two B-cell neoplasms.

Adult↗
PubMed1984

Synthesis of bovine growth hormone by Streptomyces lividans.

Streptomyces lividans 66 was transformed with a plasmid containing the regulatory region of the Streptomyces fradiae aph gene and a structural gene that specifies bovine growth hormone (bGH). When grown in liquid culture the transformant contained a protein identical to authentic bGH, as judged by radioimmunoassay and immuno-blotting (Western analysis). The bGH was present in cells that had been in culture for up to four weeks but was not found in the medium. The strategy employed should be generally applicable to the expression of foreign genes in actinomycetes.

Animals↗
PubMed1983

The origin of replication of plasmid p15A and comparative studies on the nucleotide sequences around the origin of related plasmids.

Replication of Escherichia coli plasmid p15A was examined by use of a cell extract or a mixture of three purified E. coli enzymes: RNA polymerase; RNAase H; and DNA polymerase I. In each system, replication initiates at any of three consecutive nucleotides located at a unique site. Primer transcription starts 508 bp upstream of the replication origin. The region between 294 and 524 bp upstream of the origin determines the incompatibility property. This region specifies an RNA (RNA I) of about 105 nucleotides that is involved in regulation of primer formation. We compare the nucleotide sequences around the origins of related plasmids p15A, ColE1, pBR322, RSF1030 and CloDF13, and discuss the significance of possible RNA secondary structures in primer formation.

Base Sequence↗
PubMed1982

A viral antigen as a marker for the prognosis of human breast cancer.

An antigen present in human breast tumor cells, and which is immunologically related to the envelope protein (gp52) of murine mammary tumor virus, was used as a marker for the detection of breast cancer in an Israeli population. The results show that the antigen was detectable in 128 of 204 breast carcinomas tested (62.7%). The immunological reaction was not detected in normal breast tissue, benign breast tumors, ductal hyperplasia or in primary malignancies in other organs. A significantly higher percentage of cases with demonstrable antigen was found in Israeli women born in North Africa (78%) as compared to women of European origin (60.6%). The frequency of detection of the antigen was higher in stage IV (80%) as compared to stage I (15%), suggesting that the gp52 cross-reacting antigen is a marker for the severity of the disease. Moreover, a retrospective study of 97 cases of stage II breast cancer shows that if the antigen is detected at the time of mastectomy, one can usually predict an unfavorable prognosis. Survival data analysis indicates that patients without detectable antigen survived significantly longer than those with a detectable antigen.

Adult↗
PubMed1982

Specific cleavage of the p15A primer precursor by ribonuclease H at the origin of DNA replication.

We report studies on the mechanism of initiation of DNA replication by p15A, a small plasmid whose origin of replication is known to function much as does that of ColE1. Previous work has shown that an RNA primer for DNA synthesis is generated by the action of RNase H (EC 3.1.26.4) on a precursor transcript. The precursor initiates well upstream of the origin of replication and somehow forms a hybrid with its template during transcription. Here we show that when RNase H cleaves the hybrid at 0 degrees C, an additional cleavage product besides the primer can be identified. Using two-dimensional RNA sequencing techniques, we have established the sequence of this product to within a few nucleotides of each end. The position of the 5' end indicates that the nuclease introduces a nick or very small gap in the precursor at the origin. This suggests that some sequence or structure directs the enzyme to the origin. The position of its 3' end indicates that the precursor terminates at or near a series of six dAs in the template strand about 190 nucleotides from the origin of replication. The data indicate that hybrid formation may be necessary for termination of the precursor at this downstream site.

Base Sequence↗
PubMed1981

In vivo expression of the rII region of bacteriophage T4 present in chimeric plasmids.

The expression of the T4 rII genes in uninfected cells has been examined by use of recombinant plasmids. Hybridization analysis of pulse-labelled RNA prepared from cells carrying pTB101, a plasmid that contains the end of T4 gene 60 and the beginning of gene rIIA, shows that about 0.7% of the labelled RNA is rII specific. By contrast, only 0.02% of pulse-labelled RNA prepared from cells carrying plasmid pTB301, which probably contains the middle-mode rIB promoter, may be rII specific. When separated strands of T4 DNA were used for hybridization, we found that the pTB101 transcripts have a strand specificity identical to that of the rIIA transcripts made during phage infection. The same strand specificity was observed irrespective of the orientation of the inserted DNA in the vector. This result argues that the transcripts initiate within the inserted DNA rather than somewhere else on the plasmid. We also found that essentially none of the pulse-labelled pTB101 RNA would hybridize to the DNA of a T4 deletion mutant that lacks the rIIA gene. This suggests that little of the gene 60 DNA of the plasmid is being transcribed. In addition to the rII transcript, a new protein of 56,000 Daltons molecular weight is found in cells carrying pTB101. Fingerprint analysis of the protein shows that it is specified by the rIIA gene of the plasmid. Taken together, these results indicate that transcription of the plasmid rIIA gene initiates at or near the beginning of the gene.

DNA, Viral↗
PubMed1981

Inhibition of ColE1 RNA primer formation by a plasmid-specified small RNA.

Transcription of ColE1 DNA by RNA polymerase in vitro starts at two sites in a region required for maintenance of the plasmid. Certain transcripts that start at one of the sites can be cleaved by RNase H and then act as primers for DNA replication. Transcription from the other site produces a RNA approximately 108 nucleotides long (species I or RNA I). Transcripts analogous to the primer and RNA I of ColE1 are produced when p15A or small derivatives of two other ColE1-compatible plasmids, CloDF13 and RSF1030, are used as template. If purified RNA I is added to the transcription reaction containing RNase H, formation of primer is inhibited. Each RNA I can inhibit primer formation by the plasmid that specifies it but has no effect on primer formation by heterologous templates. Thus, the inhibition of primer formation by RNA I is incompatibility specific. Because RNA I does not inhibit initiation or propagation of transcription or the processing of preformed precursors, the step that is sensitive to inhibition is probably formation of the hybrid between the primer precursor and the template. This hybrid is the required substrate for RNase H. Experiments with recombinant plasmids show the region that determines the specificity of response to RNA I to be greater than 300 base pairs upstream of the origin of DNA replication.

Base Composition↗