Glass bead implantation in the scleral cavity during evisceration.
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Biomedical subjects
Publications and source records attributed to N Rosen.
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Between 1977 and 1980, 854 biopsied cases of benign breast disease (BBD) and 755 matched surgical and 723 matched neighborhood controls subjects were interviewed in Israel by using a detailed food frequency questionnaire. Cases were classified according to degree of ductal atypia (Black-Chablon grading system). Women with atypic lesions (grades greater than or equal to 3) reported a higher intake of all types of foods compared with both control series. Further analyses indicated that the increased consumption was due primarily to foods containing greater than or equal to 10% fat. Odds ratios associated with the highest fat consumption quartile were close to 3.0. There was a trend for increasing saturated fatty acid consumption with increasing ductal atypica. After adjusting for hormonal and demographic confounders, the association with fat intake was strengthened. Because atypic BBD has been reported to be a precursor of breast cancer, our findings lend support to the hypothesis that dietary fat is a risk factor for breast cancer.
The lck protein tyrosine kinase is normally expressed in a cell type-specific fashion, with mRNA being confined to cells of lymphoid lineage. Despite this highly specific pattern of expression in normal tissues, lck mRNA has also been detected in selected cell lines derived from human nonlymphoid neoplasms. In this study we explored the mechanisms underlying the expression of lck mRNA within human nonlymphoid neoplastic cell lines. We determined that lck mRNA expression was correlated with transcriptional activation and that there was no evidence for genomic rearrangement or amplification within the lck coding region to account for the expression of lck mRNA in the nonlymphoid neoplastic cell lines. The lck gene has previously been shown to contain two distinct promoter elements. In this study, we demonstrated that lck-producing cell lines derived from human nonlymphoid neoplasms expressed transcripts initiated exclusively from the 3'-most promoter element (3' promoter). In contrast, lymphoid cell lines derived from nonmalignant sources expressed lck transcripts exclusively initiated from the 5'-most promoter element (5' promoter). Most cell lines derived from human lymphoid neoplasms express lck transcripts initiated from both the 5' and 3' promoters in various ratios. Thus, lck expression in a variety of malignant cell lines results from a selective induction of transcription from the 3' promoter.
Insulin-like growth factor I (IGF-I) activity has been reported to be produced by several human cancers. Identification of RNAs transcribed from the IGF-I gene has been complicated by the detection of multiple hybridizing bands on Northern analysis. To determine if any of these RNAs are transcribed from the IGF-I gene, we have used a sensitive and specific ribonuclease (RNAse) protection assay for IGF-I. We have also studied the breast cancer tissue expression of IGF-I using in situ hybridization histochemistry. We have found no IGF-I mRNA in breast (zero of 11) or colon cancer (zero of 9) cell lines; both of these tumors have been previously reported to express IGF-I mRNA. However, three of three neuroepithelioma and one of two Ewing's sarcoma cell lines express IGF-I mRNA; therefore, in these tumors IGF-I may be an autocrine growth factor. In contrast to breast cancer cell lines, RNA extracted from breast tissues has easily detectable IGF-I mRNA. In situ hybridizations show that IGF-I mRNA is expressed in the stromal cells, and not by normal or malignant epithelial cells. These findings suggest that although IGF-I is not produced by breast epithelial cells it may function as either a paracrine stimulator of epithelial cells or an autocrine stimulator of stromal cells.
Laboratory evidence is presented that estrogens are able to induce the production of numerous growth factors which can act in an autocrine or paracrine fashion in estrogen dependent breast cancer. Estrogen independent tumors can produce these same growth factors constitutively and so escape the need for estrogen stimulation. Growth inhibitory factors such as TGF-beta can also be controlled by estrogens and antiestrogens. It is unclear at present, however, how much of the cytostatic effect of antiestrogens in vivo is explained by the production of growth inhibitors. The overall control of breast cancer growth is mediated by the combined effects of these growth stimulatory and inhibitory factors in both breast stroma and epithelium. Interruption of the action of growth factors and the use of growth inhibitors may provide opportunities for new approaches to the treatment of breast cancer.
We examined the expression, abundance, and protein kinase activity of pp60c-src in two different pairs of genetically indistinguishable cloned human neuroblastoma cell variants which display altered phenotypes as the result of conversion from a neuronal to a non-neuronal phenotype. The results demonstrate that cells which exhibit the neuroblastic (N-type) phenotype possess high levels of pp60c-src protein and that one of the two N-type cell lines is capable of expressing the neuronal-specific isoenzyme of pp60c-src. In contrast, cells which display the substrate-adherent (S-type) phenotype have low levels of pp60c-src protein and express exclusively the non-neuronal isoenzyme of pp60c-src. In all cells examined the abundance of pp60c-src was found to be proportional to the steady-state level of c-src RNA. In each case the protein kinase activity of pp60c-src was found to be proportional to the abundance of the protein and independent of the ratio of neuronal to non-neuronal species of pp60c-src.
The effects of butyrate-mediated differentiation of human colon carcinoma cells on the expression of src-related tyrosine protein kinases were analyzed. The results demonstrate that treatment of a variety of colon carcinoma cell lines with 2 mM sodium butyrate resulted in diminished population doubling rates, altered morphology, decreased anchorage-independent growth, and increased expression of colon epithelial differentiation marker enzymes such as alkaline phosphatase. In butyrate-treated cells, significantly diminished protein kinase activities and abundance of pp60c-src and p56lck were found to parallel the butyrate-induced phenotypic alterations. For the lck gene, the decreased levels in p56lck abundance were found to coincide with diminished levels of steady-state lck mRNAs. In contrast, treatments which arrested the growth of the colon carcinoma cells without inducing differentiation had no effect on the level of expression of these proteins. Furthermore, colon carcinoma cell lines which were found to be resistant to butyrate-induced differentiation showed no change in the kinase activity or abundance of either protein following butyrate treatment. These results indicate that the expression of several src-related kinases in human colon carcinoma can be influenced by the differentiation state of the cells.
The pattern of insulin-like growth factor II (IGF-II) mRNA expression in developing kidney and Wilms' tumor was examined with in situ hybridization. In developing kidney, IGF-II was primarily expressed in blastemal cells and lost with their differentiation. In triphasic Wilms' tumor, a similar relationship was found. But in a monomorphous Wilms', tumor cells with epithelial differentiation expressed IGF-II mRNA. These data suggest that IGF-II may be involved in fetal nephrogenesis, that its expression is inversely coupled to normal epithelial differentiation, and that this differentiation may be aberrantly regulated in Wilms' tumor.
Ten patients with acute meningitis caused by gram-negative bacteria were treated with pefloxacin intravenously for a mean period of 10 days. Eight patients responded clinically to pefloxacin treatment, and the causative organisms were eradicated from the cerebrospinal fluid in 9 of the 10 patients. Pefloxacin may offer a new, efficacious, and safe therapy for gram-negative meningitis.
Although acquired immunodeficiency syndrome (AIDS) remains relatively uncommon in the elderly, there are serious and unique implications associated with the diagnosis of AIDS in this age group. The most common mode of transmission is transfusion. With the growing number of elderly, an increase in AIDS in the elderly will occur despite improved screening methods. Dementia is a serious morbidity associated with AIDS in the elderly, which presents considerable diagnostic and ethical dilemmas. A case is presented which illustrates the geriatric multidisciplinary team approach to the care of a 90-year-old man with AIDS.
Two hundred fifty-three patients with chronic epiphora underwent dacryocystorhinostomy combined with silicone intubation of the lacrimal drainage system. An overall success rate of 91.3% was achieved. Since the tubes were well-tolerated postoperatively, complications were rare and benign. Although our success rate is similar to those reported for similar cases using other techniques, we find that silicone intubation facilitates surgery in cases with excessive intraoperative bleeding or nasal mucosal tears, and simplifies postoperative follow-up.
Insulin-like growth factor II is a growth factor important in fetal development. Several cancer tissues and cell lines have been reported to express IGF-II and rat IGF-II is mitogenic for breast cancer cell lines. Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblasts and in the established breast cancer cell line, T47D. In this cell line, steady state levels of IGF-II message were increased by treatment with estradiol. 10 nM IGF-II, purified from human serum, was mitogenic for breast cancer cell lines. In vitro, IGF-II may act as an autocrine growth factor for some cell lines. RNA derived from breast cancer, pathologically normal breast tissue, and benign breast disease also contained IGF-II mRNA. When paired samples of normal and cancer tissue were obtained from the breast of the same patient, the level of IGF-II mRNA expression in the normal tissue was at least that found in the cancer. This is consistent with previous observations that show IGF-II is expressed in mesenchyme. These findings suggest that in breast cancer IGF-II is produced by stromal tissue elements and potentially by the malignant epithelial cells. Therefore, IGF-II may function as an autocrine or a paracrine growth factor in different breast tumors.
Records of histopathology from the 3734 Jewish women having breast biopsy and/or operations in all Israeli hospitals during the year from July 1979 to June 1980 were reviewed. Approximately 28.5% of these women were diagnosed as having breast cancer and 71.5% as having benign breast disease: 48.5% had benign proliferative mastopathy (BPM), 16.6% had fibroadenoma (FA) without coexistent BPM, and 6.4% had other benign breast conditions. The age-specific incidence rate was 66 in 100,000 for breast cancer and 165.2 in 100,000 for benign breast disease. Native European or American women and native Israeli women had significantly higher age standardized incidence rates of both breast cancer and BPM, but not of FA, as compared to African/Asian-born women (P less than 0.01). Age-related ratios between invasive to precursor breast lesions were similar in all ethnic groups. The data suggest that breast cancer and benign proliferative mastopathy may have a common etiologic component.
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The mechanisms by which human breast cancers regulate their own growth have been studied by us in an in vitro model system. We showed that specific growth factors (IGF-I, TGF alpha, PDGF) are secreted by human breast cancer cells. A variety of experiments suggest that they are involved in tumor growth and progression. These activities are induced by estradiol in hormone-dependent breast cancer cells and secreted constitutively by estrogen-independent cells. Concentrates of conditioned medium derived from breast cancer cells can induce the growth of hormone-dependent cells in vivo in athymic nude mice. Hormone-dependent breast cancer cells also secrete TGF beta. TGF beta is growth inhibitory. Growth inhibitors such as antiestrogens or glucocorticoids increase TGF beta secretion. An antiestrogen-resistant mutant of MCF-7 cells does not secrete TGF beta when treated with antiestrogen, but is growth inhibited when treated with exogenous TGF beta. Thus, TGF beta functions as a negative autocrine growth regulator and is probably responsible for some of the growth inhibitory effects of antiestrogens.
Twenty-five male patients with nongonococcal urethritis including 15 chlamydial infections, were treated with spiramycin for ten days. All but four patients had been treated previously, mostly with tetracyclines. Chlamydia trachomatis was cultured in seven patients and was detected in three additional men by immunofluorescent smear. Five other patients had antibodies to chlamydia, and one patient yielded a positive culture for Ureaplasma urealyticum and Mycoplasma hominis. A successful clinical response was observed in 64% of the patients; C. trachomatis was eradicated from six of seven patients with positive cultures and the three positive direct smears were negative after treatment. It is concluded that spiramycin can be used effectively for the therapy of acute nongonococcal urethritis, as well as in patients who have failed to respond to previous treatment with tetracyclines and erythromycin.
A rare case of thyroid carcinoma presenting as an orbital tumor is described. The diagnosis was made only through histopathologic examination of tissues removed during craniotomy. Thyroid scan confirmed the diagnosis. Thyroid carcinoma should be suspected in cases of orbital metastasis of unknown origin.
An MCF-7 human breast cancer cell line was selected which was 200-fold more resistant to Adriamycin than the wild type cell line. This Adriamycin-resistant (AdrR) cell line exhibited a multidrug-resistant phenotype and was cross-resistant to a wide range of antineoplastic agents including Vinca alkaloids, anthracyclines, and epipodophyllotoxins. Cytogenetic analysis of the AdrR cell line showed the presence of homogeneously staining regions on several chromosomes which were not present in the parental cell line. Using the technique of in-gel renaturation, DNA sequences which were amplified 50- to 100-fold in the AdrR cell line and which covered a total of over 140 kilobases were isolated. In addition, AdrR cells were found to contain amplified and overexpressed sequences which were homologous to hamster P-glycoprotein gene sequences. A hamster cDNA P-glycoprotein gene probe was used to screen a lambda gt10 cDNA library made from human AdrR cell line mRNA and human cDNA sequences homologous to the P-glycoprotein gene were isolated. Hybridization studies with the cloned human cDNA (pADR1) showed that the AdrR MCF-7 cell line contained a 60-fold amplification of this DNA sequence and that polyadenylated mRNA from the AdrR cell line contained a 4.8-kilobase transcript which was overexpressed 45-fold. There was a direct correlation between DNA and RNA copy number of this sequence and level of resistance among several MCF-7 Adriamycin-resistant cell lines. In situ hybridization studies demonstrated that the human P-glycoprotein gene sequence was found on chromosome 7q21.1 in normal human lymphocytes and that amplified DNA sequences isolated from the AdrR MCF-7 cells by the in-gel hybridization technique were linked to the human P-glycoprotein sequences in the homogeneously staining regions in the AdrR cells.