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Biomedical subjects

C Cohen

Publications and source records attributed to C Cohen.

At least 91 records · Page 5Linked to original sources
PubMed2000

Immunolocalization of activated transforming growth factor beta1 in juvenile nasopharyngeal angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a histologically benign, locally aggressive neoplasm of the nasopharynx that exclusively affects male adolescents. It is known to be sensitive to androgens, but there are likely intermediary cytokines and/or growth factors that mediate aggressive stromal cell proliferation and angiogenesis. Transforming growth factor beta1 (TGF-beta1) is a polypeptide that is secreted in an inactive form, cleaved to produce an active form, and then deactivated in the tissues. It activates fibroblast proliferation and is known to induce angiogenesis. OBJECTIVES: To evaluate the presence of activated TGF-beta1 within the stroma of JNA specimens and to quantify the percentage of JNA specimens expressing the active growth factor. DESIGN: Immunohistochemical analysis was performed on 19 specimens of JNA using a unique antibody that identifies only the activated form of TGF-beta1. The percentage of cells staining positively for activated TGF-beta1 was determined semiquantitatively by visual methods. RESULTS: Of 19 cases stained, all 19 (100%) showed strong positive staining (2 cases with 33%-66% of cells staining and 17 with 66%-100% of cells staining). Activated TGF-beta1 was identified in stromal cell nuclei and cytoplasm and in the endothelium of the capillaries within all specimens of JNA. CONCLUSIONS: The localization of activated TGF-beta1 to the fibroblasts and endothelial cells within JNA tumors suggests that TGF-beta1 may play a role in the stromal cell proliferation and angiogenesis associated with JNA. Additional receptor studies and more quantitative methods of analysis are needed to further define the role of TGF-beta1 in the pathogenesis of JNA.

Adolescent↗
PubMed2000

Use of a novel marker, calponin, for myoepithelial cells in fine-needle aspirates of papillary breast lesions.

Benign and malignant papillary lesions of the breast (PBL) can be difficult to distinguish in fine-needle aspirates (FNA). This study evaluates the use of smooth muscle actin (SMA) and a new smooth muscle-specific protein, calponin, for identifying myoepithelial cells (MEC) by immunohistochemical methods in paraffin-embedded cell blocks of FNA of PBL. Formalin-fixed, paraffin-embedded cell blocks of 40 cases of PBL were stained using SMA and calponin, steam heat-induced epitope retrieval, and an avidin biotin-complex technique. Staining was evaluated in MEC, epithelial, and stromal cells. The diagnosis of benign vs. malignant papillary lesion was made by using cytomorphological criteria and the presence/absence of MEC in the cell block. These results were compared to the original cytologic and subsequent histologic diagnoses. Of 40 cases of FNA diagnosed as PBL, there were 27 intraductal papillomas (IP), 6 papillary lesions with atypical features (PLAF), and 7 papillary carcinomas (PC). In all of the IP, MEC stained both with SMA and calponin. None of the PC cases was positive for MEC with calponin, and 2 out of 7 cases were weakly positive by SMA. In 6 cases of PLAF, 2 were negative for MEC, both by SMA and calponin, and a malignant papillary lesion was confirmed by histology. The remaining 4 cases were positive for MEC with both markers and were confirmed to be benign by histology. SMA stained stromal cells strongly in all of the cases where stroma was present (18 of a total of 40 cases of PBL), while calponin stained stroma focally in only 7 cases. More than half of all cases had nuclear staining of epithelial cells with SMA; calponin did not show any nuclear staining.

Actins↗
PubMed2000

Sentinel node staging of early breast cancer using lymphoscintigraphy and the intraoperative gamma-detecting probe.

Sentinel node staging for breast cancer is increasingly used in place of axillary lymph node dissection but is not yet universally accepted. The problems of non-standardized methodologies and lack of consensus on the optimum techniques to identify sentinel nodes are being addressed. Complementary use of radionuclide imaging before surgery, intraoperative probe detection, and blue dye have yielded the best reported sensitivities for finding a sentinel node (94%). The importance of imaging is summarized as identifying sentinel node(s), distinguishing sentinel from secondary nodes, guiding surgical incision planning, and facilitating lower doses. The learning curve phenomenon, which applies to the surgeon and the nuclear medicine physician, has been recognized; measures to minimize it are being implemented. Radiation exposure to operating room and pathology personnel is very low; estimates of exposure to the surgeon's hands are 0.2% of the annual whole body dose received by every human being from natural background and cosmic sources.

Breast Neoplasms↗
PubMed2000

Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia.

The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification. A total of 120 papillary urothelial pTa and pT1 tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression in stage with CK20 and CD44 immunoreactivity were assessed. WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as well as in the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior in patients with papillary urothelial pTa and pT1 neoplasms.

Adult↗
PubMed2000

Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: correlation with Gleason staging.

We recently reported that the mutant form of the tumor-suppressor gene p53 up-regulates 15-LO-1 gene expression in a murine cell line. Here, we examine the expression of 15-lipoxygenase (LO)-1 and mutant p53 (mtp53) in human prostatic tissues and 15-LO-1 in the human prostate adenocarcinoma cell line PC-3. Reverse transcription-PCR and western analyses conclusively demonstrated expression of 15-LO-1 in PC-3 cells. Western blotting for 15-LO-1 in freshly resected 'normal' and prostate adenocarcinoma specimens showed 15-LO-1 expression in normal tissue, but significantly higher levels were detected in prostate adenocarcinomas. Prostate adenocarcinoma tissues generated chirally pure 13-S-hydroxyoctadecadienoic acid from exogenous linoleic acid, a preferred substrate of 15-LO-1. To study the correlation of 15-LO-1 expression with mtp53 in prostate cancer, we immunostained 48 prostatectomy specimens obtained by transurethral resection of the prostate and needle biopsy (median age 68 years, range 52-93) of different Gleason grades (n = 48), using antibodies specific for 15-LO-1, mtp53 and MIB-1 (a proliferation marker). We compared staining in cancerous foci with adjacent normal appearing prostate tissues. In only 5 of 48 patients did 'normal' tissue adjacent to cancerous foci display staining for 15-LO-1. However, no staining for mtp53 was observed in any of the normal tissues. In cancer foci, robust staining was observed for both 15-LO-1 (36 of 48, 75%) and mtp53 (19 of 48, 39%). Furthermore, the intensities of expression of 15-LO-1 and mtp53 correlated positively with each other (P < 0.001) and with the degree of malignancy, as assessed by Gleason grading (P < 0.01). By immunohistochemistry, 15-LO-1 was located in secretory cells of peripheral zone glands, prostatic ducts and seminal vesicles, but not in the basal cell layer or stroma. Based on these and other studies, we propose a model describing a possible role for 15-LO-1 expression in influencing the malignant potential and pathobiological behavior of adenocarcinomas.

Adenocarcinoma↗
PubMed2000

Circulating natural killer cells in retired asbestos cement workers.

The effect of past exposure to asbestos on natural killer (NK) cell number and activity is uncertain. We measured NK cell number and activity in 1052 retired asbestos workers without symptomatic lung disease, lung cancer, or mesothelioma and with a long latency period from exposure; results were compared with those for 100 healthy age-matched controls. The exposed workers showed a decreased NK cell activity and increased NK cell number, yielding a 10.8 higher odds ratio for low NK activity per cell compared with controls (95% confidence interval 6.4 to 18.4), which was due to both a decrease in NK cell activity and an increase in NK cell number. Asbestos exposure of 10 years or more increased the risk of low NK activity per cell. We conclude that exposure to asbestos is associated with diminished effectiveness of NK cells and a concomitant increase in the number of NK circulating cells.

Aged↗
PubMed2000

Bioactive glass granules for regeneration of human periodontal defects.

PURPOSE: A comparative study which evaluated the effectiveness of bioactive glass granules of uniform size (300-335 microns) for the regenerative treatment of interproximal intrabony periodontal defects was conducted. MATERIALS AND METHODS: Twelve pairs of advanced periodontal lesions in 12 patients (6 males and 6 females) were treated in a split-mouth design with open flap débridement in the control sites and open flap débridement with bioactive glass particles placed in the test sites. RESULTS: At 6 months post-treatment, both treatment modalities demonstrated a gain in clinical attachment level (CAL), with the test sites having a significantly (p < .01) greater gain in CAL than the control sites. Reentry procedures were performed to assess the amount of hard tissue fill. The test sites demonstrated significantly (p < .001) more gain in hard tissue fill than the controls.

Adult↗
PubMed2000

Electrokinetically controlled microfluidic analysis systems.

Electrokinetic forces are emerging as a powerful means to drive microfluidic systems with flow channel cross-sectional dimensions in the tens of micrometers and flow rates in the nanoliter per second range. These systems provide many advantages such as improved analysis speed, improved reproducibility, greatly reduced reagent consumption, and the ability to perform multiple operations in an integrated fashion. Planar microfabrication methods are used to make these analysis chips in materials such as glass or polymers. Many applications of this technology have been demonstrated, such as DNA separations, enzyme assays, immunoassays, and PCR amplification integrated with microfluidic assays. Further development of this technology is expected to yield higher levels of functionality of sample throughput on a single microfluidic analysis chip.

Chemistry Techniques, Analytical↗
PubMed2000

Residual beta-cell function and microvascular complications in type 1 diabetic patients.

To determine the influence of residual beta-cell function on retinopathy and microalbuminuria we measured basal C-peptide in 50 type 1 diabetic outpatients aged 24.96 +/- 7.14 years, with a duration of diabetes of 9.1 +/- 6.2 years. Forty-three patients (86%) with low C-peptide (<0.74 ng/ml) had longer duration of diabetes than 7 patients (14%) with high C-peptide (> or =0.74 ng/ml) (9 (2-34) vs 3 (1-10) years, P = 0.01) and a tendency to high glycated hemoglobin (HBA1) (8.8 (6-17.9) vs 7.7 (6.9-8.7)%, P = 0. 08). Nine patients (18%) had microalbuminuria (two out of three overnight urine samples with an albumin excretion rate (AER) > or =20 and <200 microg/min) and 13 (26%) had background retinopathy. No association was found between low C-peptide, microalbuminuria and retinopathy and no difference in basal C-peptide was observed between microalbuminuric and normoalbuminuric patients (0.4 +/- 0.5 vs 0.19 +/- 0.22 ng/ml, P = 0.61) and between patients with or without retinopathy (0.4 +/- 0.6 vs 0.2 +/- 0.3 ng/ml, P = 0.43). Multiple regression analysis showed that duration of diabetes (r = 0. 30, r2 = 0.09, P = 0.031) followed by HBA1 (r = 0.41, r2 = 0.17, P = 0.01) influenced basal C-peptide, and this duration of diabetes was the only variable affecting AER (r = 0.40, r2 = 0.16, P = 0.004). In our sample of type 1 diabetic patients residual ss-cell function was not associated with microalbuminuria or retinopathy.

Adult↗
PubMed2000

Altered basic fibroblast growth factor expression in common epidermal neoplasms: examination with in situ hybridization and immunohistochemistry.

BACKGROUND: The fibroblast growth factor family consists of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and Kaposi fibroblast growth factor (kFGF). The distribution of these growth factors in skin disease has not been determined. OBJECTIVE: The purpose of this study was to determine the distribution of these growth factors in keratinocytic lesions and normal skin. METHODS: Skin sections from common disorders of keratinocytes were examined by in situ hybridization with specific probes for aFGF, bFGF, and kFGF, and immunohistochemistry. RESULTS: Of the growth factors studied, only bFGF was present in skin. bFGF messenger RNA was highly expressed in both normal epidermis and benign and malignant epithelial neoplasms. In normal skin, bFGF was expressed predominantly in a suprabasal fashion, whereas in epithelial neoplasms, homogeneous high-level expression of bFGF was observed. CONCLUSION: bFGF is the primary member of the fibroblast growth factor expressed in the skin. The source of synthesis of bFGF is keratinocytes. Immunoreactivity for bFGF appears to be primarily confined to upper layers of the epidermis in normal skin, but is expressed at all layers of the epidermis in both benign and malignant neoplastic conditions. Genetic changes that promote epithelial tumors may also promote translation of bFGF messenger RNA into protein. Specific inhibition of bFGF activity may have application in the treatment of common skin diseases.

Epidermis↗
PubMed2000

[Duodenal somatostatinomas associated with von Recklinghausen's neurofibromatosis. Apropos of 2 cases].

Somatostatinomas are rare neuroendocrine tumors; they are essentially located in the pancreas and in the duodenum. The association with a neurofibromatosis type I is especially observed when the tumor is located in the ampulla of Vater. These tumors are not associated with a "somatostatin syndrome", but often present with gastrointestinal bleeding, abdominal pain and obstructive jaundice. The diagnosis is confirmed by immunohistochemical studies. The aim of this study is to report 2 cases of metastazing duodenal periampullary somatostatinomas associated with von Recklinghausen's disease and to discuss the prognosis of these tumors. Future genetic research are necessary as point out the familial feature of this association in one of our cases.

Duodenal Neoplasms↗
PubMed1999

Disabled-2 inactivation is an early step in ovarian tumorigenicity.

Disabled-2 (Dab2) functions in mitogenic signal transduction pathway, and is frequently activated by homozygous gene deletion in tumors, suggesting that Dab2 is a candidate tumor suppressor. Here, we surveyed the expression of Dab2, and report that Dab2 is expressed in a variety of tissues, and the level of expression is particularly high in ovary and breast. Dab2 expression was also detected in immortalized breast and ovarian epithelial cells. However, in more than a dozen established tumor cell lines derived from breast and ovarian epithelial tumors examined by Western blotting, Dab2 expression was undetectable in 90% of these cell lines. Histological staining of human ovarian tissues with specific anti-Dab2 antibodies indicated that Dab2 is highly expressed in the surface epithelial layer. In an immunohistological study of 26 ovarian carcinomas, 22 (85%) of the tumors were found to lose the expression of Dab2 in the tumor cells, which are epithelial origin. Loss of Dab2 expression is not correlated with tumor grade, suggesting that Dab2 is lost in an early stage of tumorigenicity. Indeed, loss of Dab2 correlates closely with morphological transformation of the surface epithelial cells. Additionally, loss of Dab2 protein occurs in hyperproliferative, but histological benign ovarian epithelium, suggesting that loss of Dab2 occurs in pre-malignant lesions. Thus, this study indicates that the loss of Dab2 expression is correlated with tumorigenicity of the cells disregarding the grade of the tumors, and loss of Dab2 expression is an early event in ovarian malignancies.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Atomic structure of scallop myosin subfragment S1 complexed with MgADP: a novel conformation of the myosin head.

The crystal structure of a proteolytic subfragment from scallop striated muscle myosin, complexed with MgADP, has been solved at 2.5 A resolution and reveals an unusual conformation of the myosin head. The converter and the lever arm are in very different positions from those in either the pre-power stroke or near-rigor state structures; moreover, in contrast to these structures, the SH1 helix is seen to be unwound. Here we compare the overall organization of the myosin head in these three states and show how the conformation of three flexible "joints" produces rearrangements of the four major subdomains in the myosin head with different bound nucleotides. We believe that this novel structure represents one of the prehydrolysis ("ATP") states of the contractile cycle in which the myosin heads stay detached from actin.

Adenosine Diphosphate↗
PubMed1999

Ritonavir and saquinavir combination therapy for the treatment of HIV infection.

OBJECTIVE: To evaluate the safety and antiretroviral activity of ritonavir (Norvir) and saquinavir (Invirase) combination therapy in patients with HIV infection. DESIGN: A multicenter, randomized, open-label clinical trial. SETTING: Seven HIV research units in the USA and Canada. PATIENTS: A group of 141 adults with HIV infection, CD4 T lymphocyte counts of 100-500 x 10(6) cells/l, whether treated previously or not with reverse transcriptase inhibitor therapy, but without previous HIV protease inhibitor drug therapy. INTERVENTIONS: After discontinuation of prior therapy for 2 weeks, group I patients were randomized to receive either combination (A) ritonavir 400 mg and saquinavir 400 mg twice daily or (B) ritonavir 600 mg and saquinavir 400 mg twice daily. After an initial safety assessment of group I patients, group II patients were randomized to receive either (C) ritonavir 400 mg and saquinavir 400 mg three times daily or (D) ritonavir 600 mg and saquinavir 600 mg twice daily. Investigators were allowed to add up to two reverse transcriptase inhibitors (including at least one with which the patient had not been previously treated) to a patient's regimen after week 12 for failure to achieve or maintain an HIV RNA level < or = 200 copies/ml documented on two consecutive occasions. MEASUREMENTS: Plasma HIV RNA levels and CD4+ T-lymphocyte counts were measured at baseline, every 2 weeks for 2 months, and monthly thereafter. Safety was assessed through the reporting of adverse events, physical examinations, and the monitoring of routine laboratory tests. RESULTS: The 48 weeks of study treatment was completed by 75% (106/141) of the patients. Over 80% of the patients on treatment at week 48 had an HIV RNA level < or = 200 copies/ml. In addition, intent-to-treat and on-treatment analyses revealed comparable results. Suppression of plasma HIV RNA levels was similar for all treatment arms (mean areas under the curve minus baseline through 48 weeks were-1.9, -2.0, -1.6, -1.8 log10 copies/ml in ritonavir-saquinavir 400-400 mg twice daily, 600-400 mg twice daily, 400-400 mg three times daily, and 600-600 mg twice daily, respectively). Median CD4 T-lymphocyte count rose by 128 x 10(6) cells/l from baseline, with an interquartile range (IQR) of 82-221 x 10(6) cells/l. The most common adverse events were diarrhea, circumoral paresthesia, asthenia, and nausea. Reversible elevation of serum transaminases (> 5 x upper limit of normal) occurred in 10% (14/141) of the patients enrolled in this study and was associated with baseline abnormalities in liver function tests, baseline hepatitis B surface antigen positivity, or hepatitis C antibody positivity (relative risk, 5.0; 95% confidence interval 1.5-16.9). Most moderate or severe elevations in liver function tests occurred in patients treated with ritonavir-saquinavir 600-600 mg twice daily. CONCLUSIONS: Ritonavir 400 mg combined with saquinavir 400 mg twice daily with the selective addition of reverse transcriptase inhibitors was the best-tolerated regimen of four dose-ranging regimens and was equally as active as the higher dose combinations in HIV-positive patients without previous protease inhibitor treatment.

Adult↗
PubMed1999

Interphase fluorescence in situ hybridization studies of ovarian adenocarcinomas using the midisatellite probe.

The genes involved in ovarian carcinogenesis are largely unknown. Cytogenetic studies have shown a large number of chromosomal abnormalities in ovarian cancers. Molecular studies have additionally found abnormalities. Few in situ hybridization studies have been performed on ovarian cancer tissues. We chose to study the distal region of chromosome 1p with the midisatellite probe and interphase fluorescence in situ hybridization. A total of 35 patient samples, including various controls and cancers, was collected from our pathology archives. Our cancer cases included some patients with stage I disease, in whom tumors arose in endometriotic cysts. In these cases, both tumor tissue and areas in the cyst distant from the tumor mass were examined. Results showed clear cell carcinoma nuclei to have an increase in both number and size of probe signals, interpreted as representing amplification of the probed region of chromosome 1. Serous carcinomas showed an increase in the number of signals, up to four. We felt this could be a result of amplification, or, because these cells exhibited the highest mitotic counts, to DNA doubling in preparation for mitosis. Endometrioid carcinomas resembled controls in showing up to two small probe signals, but not more. We conclude that amplification in distal chromosome 1p occurs in ovarian clear cell, and possibly serous, carcinomas and may not be important in endometrioid carcinomas. Because alteration was not found in the various control epithelia, including nonmalignant-looking areas from cysts which also contained cancer, we believe that the change, when present, may not be an early step in carcinogenesis.

Adenocarcinoma↗