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Biomedical subjects

C Cohen

Publications and source records attributed to C Cohen.

At least 235 records · Page 13Linked to original sources
PubMed1991

Immunohistochemical progesterone receptor assay. Measurement by image analysis.

To determine the efficiency of image analysis in immunohistochemical progesterone receptor (PgR) measurement, 94 primary breast carcinoma tissue samples were evaluated for PgR by biochemical dextran-coated charcoal assay (DCC) and an immunohistochemical method. Frozen sections immunostained for PgR with a monoclonal antibody (Abbott PgR-ICA, Chicago, IL) and the peroxidase-antiperoxidase technique were scored semiquantitatively histologic score by microscopy and quantitatively (percentage nuclear area immunopositivity [PNA] using the CAS 200 image analyzer (Cell Analysis Systems, Elmhurst, IL). There was a positive correlation between dextran-coated charcoal assay and both histologic score (r = 0.82) and PNA (r = 0.69). Selected cutoff points of 60 histologic score and 6.5% PNA based on sensitivity/specificity calculations yielded a predictive value of a negative test of 73% and 80%, respectively, and a positive predictive value of 100% for both; ranges of fmol/mg protein PgR correspond to ranges of histologic score and PNA. The use of an image analyzer to measure PNA in PgR-immunostained sections is a viable alternative to dextran-coated charcoal assay, especially when insufficient fresh tissue is available.

Biochemistry↗
PubMed1991

Drug self-administration methods in abuse liability evaluation.

The human drug self-administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug-seeking and drug-taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self-administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self-administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self-administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherever possible.

Drug Evaluation↗
PubMed1991

Is nicotine more addictive than cocaine?

Is nicotine more addictive than cocaine? That claim is increasingly in vogue, often supported by data showing the high likelihood of progression to daily tobacco use following experimentation and the high percentage of cigarette smokers, compared with cocaine users who appear addicted. In the context of criteria for addiction of dependence presented by the World Health Organization, the American Psychiatric Association, and the US Surgeon General, we consider several lines of evidence, including patterns of mortality, physical dependence potential, and pharmacologic addiction liability measures. Within each line of evidence, we compare nicotine with cocaine. We conclude that on the current evidence nicotine cannot be considered more addicting than cocaine. Both are highly addicting drugs for which patterns of use and the development of dependence are strongly influenced by factors such as availability, price, social pressures, and regulations, as well as certain pharmacologic characteristics.

Animals↗
PubMed1991

DNA ploidy studies of benign and malignant tumours: comparison of flow cytometry and image analysis techniques using two types of cytological specimen.

DNA ploidy studies were carried out on Feulgen stained smears and cytocentrifuge preparations from 35 malignant tumours and four benign neoplasms using the CAS image analyser. The smears were prepared from scrapings from fresh tumour tissue whereas the cytocentrifuge preparations were prepared from single nuclear suspensions from paraffin-embedded cell blocks from the same tumour. Histograms obtained by image analysis of the tumour scrapes were compared with those obtained on the cytocentrifuge preparations. Concordant results were obtained in four benign tumours (100%) and 32 malignant tumours (91%). The results obtained by image analysis were also compared with results obtained by flow cytometry of the tumour tissue. Discordant results were obtained for three malignant tumours. Possible reasons for the discrepancy include sampling error, tumour heterogeneity and selective loss of cell populations during processing.

Base Sequence↗
PubMed1991

High rates of alcohol use and history of physical and sexual abuse among women outpatients.

A total of 189 consecutive new women patients were surveyed at an adult psychiatric outpatient clinic which did not have a specific program for the treatment of alcoholics. Twenty-seven patients (14%) reported a history of heavy alcohol consumption measured by scores of 10 or more on the Michigan Alcoholism Screening Test (MAST), but only 16 had a diagnosis of alcohol abuse or alcohol dependence made by a clinician. Those with a self-reported history of physical and/or sexual abuse had significantly higher scores on the MAST than those with no such history. When the first abuse occurred before the age of 18 years and there was no recent reported abuse, the association of abuse and high MAST scores persisted, suggesting that early physical or sexual abuse may be associated with current levels of alcohol use.

Adolescent↗
PubMed1991

Image analysis for quantitation of estrogen receptor in formalin-fixed paraffin-embedded sections of breast carcinoma.

Monoclonal antibody to human estrogen receptor (ER) provides a useful immunohistochemical tool for the evaluation of ER content in breast carcinoma, but visual interpretation is subjective. Computer-assisted image analysis has proved effective in immunohistochemical quantitation of ER in fresh tumor imprints and cryostat sections. We examined the usefulness of this technique in 5-microns-thick formalin-fixed paraffin-embedded tissue sections of 66 cases of primary breast carcinoma previously assayed by dextran-coated charcoal (DCC) analysis. Immunohistochemistry was automated and performed on a Code-on slide stainer (Instrumentation Laboratories, Lexington, MA) using Pronase predigestion, a monoclonal antibody (ER-ICA; Abbott, Chicago, IL), and a biotin-labeled secondary antibody. Detection was achieved with an avidin-alkaline phosphatase conjugate and nitroblue tetrazolium (NBT) bromochloroindoyl phosphate (BCIP) substrate. The immunohistochemical ER staining was analyzed visually and with the CAS/200 image analyzer (Elmhurst, IL). The visual semiquantitative histologic scores (HSCORE), the automated quantitative assays including the percentage of positive nuclear areas (PNA), and the quantitative immunocytochemical scores (QIC SCORE = PNA x % of positive stain/10) were compared with the corresponding DCC results. Linear correlations were demonstrated between all immunohistochemical assays and the logarithm of DCC, the strongest correlation seen with PNA (r = 0.91). Threshold points for positive HSCORE, QIC SCORE, and PNA assays were extrapolated using DCC as the reference. ER immunodetection by PNA as compared with visual examination alone was enhanced by 18% (up to 88%) in sensitivity and 34% (up to 94%) in specificity, and the DCC concordance rate increased by 26% (up to 91%). A comparative chart extrapolating DCC from PNA was thus established.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1991

Pulmonary blastoma with germ cell (yolk sac) differentiation: report of two cases.

Pulmonary blastoma is a rare lung neoplasm of disputed histogenesis and variable biologic behavior. Typical cases contain both epithelial and mesenchymal tissues, and a variety of patterns of differentiation have been described. While expression of oncofetal antigens in these tumors has been noted rarely, a coexisting component of germ cell tumor has not been reported previously. We describe the clinical and pathologic features of two cases of pulmonary blastoma having alpha-fetoprotein production and histologic areas of yolk sac tumor. We also report the finding of immunohistochemical staining of fetal lung tissue for alpha-fetoprotein.

Adult↗
PubMed1991

Cigarette smoking and addiction.

Tobacco use is a form of drug addiction, as shown by studies assessing the abuse liability of tobacco and nicotine in humans and animals. Tobacco experimentation frequently leads to daily use, which is characterized by a highly consistent pattern of drug intake. Such a pattern is controlled by the biologic concentrations of nicotine, a psychoactive constituent of tobacco smoke. Nicotine is a euphoriant, self-administered by humans as well as by animals in laboratory settings. Nicotine controls smokers' behavior in such a way that reducing or suppressing tobacco consumption produces a withdrawal syndrome characterized by irritability, difficulty concentrating, cognitive impairments, and weight gain. Nonpharmacologic factors are also important determinants of tobacco addiction that interfere with successful cessation. Strategies to treat tobacco addiction are comparable to those developed for other drug addictions. For example, therapy may include the use of alternate forms of nicotine and possibly also nicotine antagonists and medications targeted to alleviate specific withdrawal symptoms, if such therapies become available. As in all drug addiction treatment strategies, behavioral intervention is important whether or not a medication is used.

Animals↗
PubMed1991

Serotonin immunoreactivity in pancreatic endocrine neoplasms (carcinoid tumors).

Primary serotonin secreting pancreatic endocrine neoplasms (carcinoid tumors) are extremely rare and may be associated with manifestations of the carcinoid syndrome. Two cases of primary carcinoid tumor of the pancreas with liver metastases showed clinical and biochemical features of the carcinoid syndrome. Both cases demonstrated strong positive immunoreactivity for serotonin within the tumor cells. In an attempt to determine the relationship between pancreatic carcinoid tumors and other pancreatic endocrine neoplasms, immunostains for serotonin were performed on 11 additional islet cell tumors and on non-neoplastic pancreatic tissues. These cases showed serotonin immunoreactivity within islet cell tumors (36%). In addition, focal staining for serotonin was present in non-neoplastic ducts and ductules (88%), acini (22%), and islets of Langerhans (33%). Based on these observations, specific criteria are suggested for the diagnosis of primary pancreatic carcinoid tumor.

Adult↗
PubMed1991

Semiautomation of preparation of fixed paraffin-embedded tissue for DNA analysis.

The usual manual preparation of single-cell suspensions from fixed paraffin-embedded tissue sections for flow cytometric (FCM) DNA ploidy analysis is a time-consuming, labor-intensive technique that requires 70 minutes to deparaffinize and rehydrate 50 microns sections as the initial step. Manual deparaffinization was compared with two semiautomated methods using an automatic slide stainer with either a 70-minute or 35-minute schedule. Samples from 6 normal tissues and 21 tumors (13 diploid and 8 aneuploid) were prepared using all three methods and analyzed by FCM. The mean cell counts in all samples were over 10(6). The DNA indices for the three samples prepared from a given tissue showed no significant differences. Using the 70-minute automation schedule, no aneuploid peaks were lost, and the ratio of G0G1 normal cells to aneuploid tumor cells was maintained. The automation of deparaffinization can thus provide a significant reduction in the labor need to produce single-cell suspensions for FCM; it can be especially helpful when handling large numbers of tumors. At the same time, the automated procedure decreases the exposure to hazardous chemicals and lowers the chance of losing tissue.

DNA↗
PubMed1991

Immunohistochemical estrogen receptor assay: quantitation by image analysis.

The immunohistochemical estrogen receptor (ER) assay quantitated by image analysis was compared with the biochemical dextran-coated charcoal (DCC) assay in 97 primary breast carcinomas. Frozen sections immunostained for ER with a monoclonal antibody (ER-ICA; Abbott Laboratories, Chicago, IL) and the peroxidase-antiperoxidase technique were scored semiquantitatively by microscopy (HSCORE) and quantitatively [percentage of nuclear area immunopositivity (PNA)] using the CAS 200 image analyzer (Elmhurst, IL). There was a significant and identical correlation between DCC and both HSCORE and PNA. According to sensitivity/specificity calculations, the cut-off points of 10 for HSCORE and 1% for PNA were chosen with positive and negative predictive values of 97.7% and 74.5%, respectively. Low DCC-positive cases between 10 and 50 fmol of ER/mg of protein were immunohistochemically ER positive only in 61.5%. Immunohistochemical results of greater than 150 HSCORE and greater than 15% PNA corresponded to high DCC results of greater than 150 fmol/mg of protein. Immunohistochemical assay quantitated by image analyzer (PNA) is a comparable alternative to biochemical ER, especially when insufficient fresh tissue is available.

Breast Neoplasms↗
PubMed1990

Tumor progression in four mammary epithelial cell lines derived from the same patient.

Two primary and two metastatic cell lines with distinct phenotypes and genotypes have been established from a patient diagnosed as having infiltrating and intraductal mammary carcinoma (21T series). All four lines can be cultured in the same medium, DFCI-1, which also supports long-term growth of normal epithelial cells. Therefore, we have been able to compare normal and tumor cells at the cellular and molecular levels. The mammary origin of the 21T series was confirmed by using antibodies against the human milk fat globule antigen-2 epitope. The two primary tumor lines (21NT and 21PT) are both immortal and aneuploid, although only 21NT is tumorigenic in the nude mouse assay. The two populations derived from the metastatic pleural effusion (21MT-1 and 21MT-2) each exhibit distinct characteristics in morphology and growth factor requirements. The erbB2 gene is amplified and overexpressed in all of these cell lines compared to normal epithelial cell controls. These four tumor cell lines from a single patient represent a mammary tumor progression series that has been established in long-term cell culture.

Adult↗
PubMed1990

Case-matched comparison of mitral valve replacement and repair.

Carpentier's techniques of prosthetic ring mitral valve repair for mitral regurgitation offer the potential for immediate and long-term improvement in valve function without the necessity of replacing the native valve with a prosthesis. A consecutive, case-matched series of 65 patients with prosthetic ring mitral valve repair was compared with 65 patients undergoing mitral valve replacement for mitral regurgitation. The aortic cross-clamp time was 57 +/- 33 minutes in the repair operations and 41 +/- 25 minutes in the replacement operations (p = 0.003). The cardiopulmonary bypass time was 154 +/- 44 minutes in the repair operations and 113 +/- 41 minutes in the replacement operations (p = 0.0001). There were no myocardial infarctions in the hospital in either group. Hospital death was noted in 1.5% of repairs and 4.6% of replacements (p = not significant). Survival at 4 years was 0.84 for repairs and 0.82 for replacements (p = not significant). Freedom from reoperation to replace the mitral valve at 4 years was 62 of 65 patients in the repair group and 64 of 65 patients in the replacement group (p = not significant). In-hospital and midterm results in a closely matched population show that mitral valve repair yields results comparable with those of replacement despite a more difficult procedure. The benefits of maintaining the native valve with chordal and papillary muscle structure intact and avoidance of prosthetic valve implantation may then become apparent with longer follow-up.

Adult↗
PubMed1990

A comparative study of computerized tomography, magnetic resonance imaging, and clinical staging for the detection of early cervix cancer.

Sixteen patients with cervical cancer underwent radical surgery following standard clinical staging, MRI, and CT. The sensitivity of the CT scan was 14%, the specificity 100%. MRI had a sensitivity of 28% and a specificity of 64%. The clinical stage was correct in 10 of 16 patients (62%). CT and MRI are not individually or collectively better than clinical staging in predicting extent of disease, and currently should not be included in the FIGO staging for cervix cancer.

Adenocarcinoma↗
PubMed1990

Insulin response and glycemic effects of meals in non-insulin-dependent diabetes.

Glycemic and hormonal responses to two breakfast mixed meals were studied in six obese subjects with NIDDM. The study evaluated a high-glycemic-effect (HGE) and a low-glycemic-effect (LGE) meal, each with approximately 600 kcal and 12% protein, 15% fat, and 73% carbohydrate. Plasma insulin and counterregulatory hormones were measured at baseline and at 30-min intervals for 5 h after meals. Mean fasting plasma glucose and insulin concentrations were similar before both studies: for the LGE meal, 11.9 +/- 1.8 mmol/L and 261.9 +/- 50.1 pmol/L; for the HGE meal, 11.9 +/- 2.0 mmol/L and 262.6 +/- 43.1 pmol/L. Peak plasma glucose concentrations were approximately 25% lower with the LGE meal and the area under the glucose curve was 63% of that obtained for the HGE meal (p less than 0.05). Although the integrated insulin responses of the two meals did not differ, the peak occurred 60 min earlier in the LGE meal (p less than 0.05). The LGE meal may produce a lower glycemic response, in part because of earlier insulin secretion.

Aged↗