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Biomedical subjects

R B Cohen

Publications and source records attributed to R B Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1986

Partial purification of a nuclear protein that binds to the CCAAT box of the mouse alpha 1-globin gene.

We enriched a fraction from nuclear extracts of murine erythroleukemia cells which contains a protein able to form stable complexes with the promoter region of the alpha 1-globin gene. Binding activity, which is present in mouse brain and a variety of cultured mouse and human cell lines, is not erythroid cell specific. Binding studies with alpha-globin gene promoter deletion mutants as well as DNase I footprinting and dimethyl sulfate protection studies showed that the factor bound specifically to the CCAAT box of the alpha 1 promoter. Enriched factor preparations exhibited weak binding to the promoter region of the beta maj-globin gene. This suggests that this protein could bind differentially to these two promoters in vivo. The enriched factor may be a ubiquitous nuclear protein involved in the differential regulation of the alpha 1- and beta maj-globin genes.

Animals↗
PubMed1985

Nucleosome disruption precedes transcription and is largely limited to the transcribed domain of globin genes in murine erythroleukemia cells.

We used micrococcal nuclease to separate murine erythroleukemia cell (MELC) chromatin into soluble and insoluble fractions which differ in gene content and chromatin structure. Genes that are not expressed in the erythroid lineage, such as the Ig alpha and albumin genes, distribute preferentially into the soluble rather than the insoluble fraction, and are organized into nucleosomes in both fractions. Both alpha 1- and beta maj-globin genes are enriched in the insoluble fraction and are organized into structures that are partially devoid of nucleosomes in uninduced MELC, when the genes are transcriptionally inactive. Following chemical induction of MELC and the onset of globin gene transcription, globin gene enrichment and nucleosome disruption in the insoluble chromatin fraction increase. Using seven DNA subclones that span the beta maj-globin gene we show that insolubility and nucleosome disruption are largely limited to DNA sequences lying within the transcribed domain. Non-transcribed, flanking sequences are soluble and organized into nucleosomes. In addition, the globin genes found in insoluble, non-nucleosomal chromatin contain previously engaged RNA polymerases which can elongate globin RNA chains in vitro in a pattern qualitatively and quantitatively similar to intact nuclei. These results are discussed in terms of a model for globin gene activation during erythropoeisis.

Animals↗
PubMed1985

The use of pathologic features in selecting the extent of surgical resection necessary for breast cancer patients treated by primary radiation therapy.

The extent of the surgical resection necessary for breast cancer patients treated by primary radiation therapy is unknown. A simple gross excision of the tumor provides the best cosmetic result, but a wide local resection may be important to prevent local recurrence in some patients. In order to identify patients who are not adequately treated by gross excision of the tumor and radiation therapy, we performed a retrospective clinical-pathologic review of 221 treated women with infiltrating duct carcinoma. There were 53 cases in which the excision specimen showed a constellation of three pathologic features: prominent intraductal carcinoma in the tumor, intraductal carcinoma in the grossly-normal adjacent tissue, and poorly-differentiated nuclei. These cases had a 37% risk of a local recurrence at 6 years compared to eight per cent for all other cases (p less than 0.0001). In cases with all three features, the use of a supplemental dose of radiation to the primary site did not significantly reduce the risk of a local recurrence. Local recurrence at 6 years was 34% in cases with all three features, who received supplemental local radiation, compared to 49% in cases not receiving a supplemental dose (p = 0.28). Survival was also worse for patients with all three features compared to other cases (69% vs. 90% at 6 years, p = 0.002). These results indicate that patients with all three pathologic features have a high risk of local recurrence following gross excision of the tumor and radiation therapy. If primary radiation therapy is selected for these patients, they should first undergo a re-excision of the tumor site in order to be certain that areas of extensive intraductal carcinoma have been adequately resected. Patients whose tumors do not show all three features are adequately treated by gross excision of the tumor prior to radiation therapy.

Breast↗
PubMed1985

Detection of dihydroorotate dehydrogenase activity as a marker of de novo nucleic acid synthesis in germinal centers of spleens following antigen administration.

A histochemical technique, developed for the localization of DHO-D activity in tissue, has been utilized to study the distribution of this activity in rabbit spleen. This enzyme is involved in the de novo synthesis of pyrimidines of nucleic acids via orotic acid as an intermediate. The enzyme was found to be most active at the periphery of follicles in the resting spleen. Following antigenic challenge, enzyme activity became prominent for several days in macrophages within germinal centers, but not in the intensely pyroninophilic cells which are the dominant cell type of these structures. Antigenicity of the injected compound appeared to be necessary for the production of this effect. The pattern of localization of DHO-D is similar to the pattern of distribution of antigen within splenic tissue.

Animals↗
PubMed1984

Pathologic predictors of early local recurrence in Stage I and II breast cancer treated by primary radiation therapy.

Thirty-four gross and histologic features of the primary tumor in 231 cases of clinical Stage I and II invasive breast cancer were reviewed in an attempt to identify features which might correlate with an increased risk of local recurrence within the breast following biopsy and primary radiation therapy. Local recurrence risk at 5 years was calculated for each feature studied. While results are reported in terms of 5-year actuarial local recurrence risk, not all patients were followed for 5 years (median follow-up period, 44 months). Patients with cases in which the biopsy was less than excisional had a considerably greater actuarial risk of local recurrence at 5 years than those in which the biopsy was excisional (36% versus 8%; P = 0.0005). Among 154 infiltrating ductal carcinomas treated by excisional biopsy prior to radiotherapy, histologic features associated with a significantly increased local recurrence risk at 5 years were the combination of extensive intraductal involvement by carcinoma and high nuclear grade and/or high mitotic index. Twenty-seven tumors demonstrated this constellation of features, and there was a 5-year actuarial local recurrence risk of 39% among this group. The local recurrence risk for the remainder of the population was only 4% (P less than 0.0001). Thus, through pathologic examination of the primary, the authors identified a subgroup of patients with a considerably increased risk of local recurrence following biopsy and primary radiotherapy.

Adult↗
PubMed1984

Radiation-induced changes in the breast.

Thirty-six postirradiation breast tissue specimens from 30 patients with breast cancer treated by primary radiation therapy were evaluated to define the effects of therapeutic doses of ionizing radiation on the residual non-neoplastic breast tissue. Breast tissue was sampled an average of 30.4 months after completion of therapy because of the development of new clinically or mammographically detectable abnormalities within the treated breasts. The average radiation dose was 6,399 rad to the primary tumor area and 4,778 rad to the remainder of the breast. Breast tissue sections from 35 nonirradiated patients served as control specimens. The most characteristic radiation effects consisted of atypical epithelial cells in the terminal duct lobular unit ( TDLU ) associated with lobular sclerosis and atrophy. These changes were present in all of the irradiated patients but varied in severity and extent among patients and within individual patients. This variation was not related to the presence or absence of carcinoma elsewhere in the specimen, radiation dose, patient age, time to postirradiation tissue sampling, or use of adjuvant chemotherapy. Epithelial atypia in larger ducts, stromal changes, and vascular changes were less frequent but were always accompanied by prominent TDLU changes. Radiation effects could usually be clearly distinguished from carcinoma involving the TDLU by the absence of both cellular proliferation and distention of the involved TDLU and by the preservation of cellular polarity and cohesion in areas of presumed radiation-induced injury. Familiarity with these changes is of considerable practical importance in that they must be distinguished from new or recurrent neoplasms.

Adult↗
PubMed1983

Electrocardiographic techniques in clinical practice.

The electrocardiogram can be an important clinical tool to the veterinary practitioner. Since the results are obtained almost instantaneously, it often gives clues as to the etiology of clinical signs long before hematologic, biochemical, and radiographic results are available. Emergency situations sometime require this type of service. Figures 3 to 21 are provided to illustrate how this diagnostic technique can be used by the clinician. The electrocardiograms have been recorded at a paper speed of 50 mm per second, 1 cm equals 1 mv, unless otherwise noted.

Animals↗
PubMed1983

Clinical-pathologic study of early breast cancer treated by primary radiation therapy.

We performed a clinical-pathologic review of 231 patients with early breast cancer treated by primary radiation therapy. There were 27 patients with infiltrating ductal carcinoma treated with excisional biopsy whose tumors showed a constellation of histologic features: moderate or marked intraductal carcinoma in the tumor, intraductal carcinoma in the adjacent tissue, and high nuclear grade. These patients had a 5-yr local tumor control rate of 61% compared to 96% for similar patients whose tumors did not show all three features. Radiation dose to the primary tumor area influenced the likelihood of local recurrence in these 27 patients: 15 of these patients received 6000 rads or more to the primary tumor area and had a 5-yr local tumor control rate of 84%, compared to 48% for the 12 patients who received less than 6000 rads. These results indicate that a subgroup of breast cancer patients can be identified that has a high risk of local recurrence when an insufficient radiation dose (i.e., less than 6000 rads) is delivered to the primary tumor area.

Actuarial Analysis↗
PubMed1982

Circulating immune complexes in primary biliary cirrhosis: interactions with lymphoid cells.

To evaluate the interactions between circulating immune complexes (CIC) and lymphoid cells in primary biliary cirrhosis (PBC), we determined (1) whether antibodies to lymphocytes in PBC serum, independent of CIC, could account for binding in the Raji cell assay for CIC and (2) whether CIC or other humoral factors in PBC serum could interact with lymphoid cells to alter their function. We found that three quarters of CIC positive PBC sera bound specifically to Raji cells via complement receptors, while only one quarter had antibodies to lymphoid cells or Raji cells devoid of complement receptors. We also demonstrated factors which inhibited cell-mediated cytotoxicity and suppressor cell activity in PBC sera; however, we found no correlation between the level and presence of CIC or of lymphocyte antibodies and the level or presence of these serum inhibitory factors. Thus, although the detection of CIC in PBC is not artifactual, the contribution of CIC and other serum factors to the other immunological aberrations in PBC remains to be elucidated.

Antibodies, Neoplasm↗
PubMed1981

Surgical pathology of hyperparathyroidism. Usefulness of fat stain and problems in interpretation.

Thirty-six adult patients with classical hyperparathyroidism had parathyroidectomy in which tissue evaluation included oil red O stains. Neutral lipid staining has been reported to distinguish hyperfunctioning parathyroid from suppressed or normal tissue. In normal glands, parathyroid chief cells show abundant coarse and fine intracytoplasmic neutral lipid droplets. In contrast, the cytoplasm of chief cells is essentially free of neutral lipid droplets in adenomatous, hyperplastic, or carcinomatous glands. This study shows that to limit or alter surgical exploration solely on the basis of the findings of the oil red O technique will lead to significant judgmental error (6/36 patients). Such errors are especially likely in the patient who has enlarged parathyroid glands containing a normal distribution of parenchymal to adipose tissue. There was excellent agreement between clinical outcome, surgical-pathological findings, and the oil red O stain in 30 cases of parathyroid adenoma, nodular hyperplasia, and a control group (12 patients) who had biopsies of normal parathyroid tissue during the course of thyroidectomy.

Adenoma↗
PubMed1979

Fistulous communication between the left coronary artery and main pulmonary artery: a thirteen-year follow-up.

A patient with a fistula producing a 2:1 left-to-right shunt between the coronary arteries and pulmonary artery followed for 13 years is described. The patient remained asymptomatic and without significant electrocardiographic, hemodynamic, or angiographic changes. Large collateral vessels were demonstrated on initial and repeat angiographic studies. This case illustrates the natural history of coronary artery to pulmonary artery shunts and suggests that surgery may not be necessary, even in the presence of a very large communication.

Angiocardiography↗
PubMed1979

Cardiac arrhythmias in the anesthetized patient.

Continuous monitoring of the electrocardiogram provides an opportunity for the veterinary surgeon to perform the surgical procedure in a safe and controlled manner. Arrhythmias can usually be eliminated by lowering the concentration of anesthetic and administering additional oxygen. Antiarrhythmic drugs are required when these measures do not control the problem and when surgery cannot be stopped. If a disturbance cannot be abolished or controlled with medication, the surgeon must weigh the potential gain of surgery against the potential risks of the arrhythmia.

Anesthesia↗
PubMed1977

Medullary carcinoma of the human thyroid in monolayer culture: morphological and cytochemical correlations.

Mechanically or enzymatically dissociated cells from three human medullary thyroid carcinomas (MTC) were grown in monolayer culture for periods up to seven months. Cultures of each tumor contained clusters of small epithelial-like cells which were readily identified by phase contrast microscopy. Immunocytochemical studies and electron microscopy showed that these cells contained abundant calcitonin and numerous secretory granules. Amine-storing mechanisms were also demonstrable in these cells by formaldehyde-induced fluorescence. Homogeneous cultures of epithelial-like cells showed no evidence of transitions into fibroblast-like cells. Addition of thyroxin to the tissue culture medium appeared to promote survival of epithelial-like cells in cultures of one tumor. The ability to morphologically recognize cultured cells with endocrine activity should facilitate establishment of human MTC lines for biochemical and physiological studies.

APUD Cells↗