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Biomedical subjects

A Rosen

Publications and source records attributed to A Rosen.

At least 145 records · Page 8Linked to original sources
PubMed1995

A CD4+ T cell line-secreted factor, growth promoting for normal and leukemic B cells, identified as thioredoxin.

In this study, a B cell growth stimulatory factor, constitutively secreted by a human CD4+ T cell hybridoma clone, MP6, has been purified and characterized. Serum-free 24 h culture media from MP6 cells were collected, concentrated by ultrafiltration and separated by gel chromatography. Fractions were analyzed for stimulatory activity using [3H]thymidine incorporation in normal and leukemic (B-CLL) B cells as target cells. Activity was present in a 12 kDa protein peak. Upon storage this lost activity indicating that the factor was sensitive to air oxidation, a well-known property of mammalian thioredoxins (Trxs). Treatment of the inactive fraction with dithiothreitol restored full activity. When culture medium was analyzed with a radioimmunoassay for human placenta Trx, the MP6 clone was shown to release 30-50 ng/ml per million cells during 24 h. The B cell stimulatory activity of the MP6 medium was removed by Sepharose-bound anti-human placenta Trx IgG and activity was recovered by elution from the antibodies. Furthermore, MP6 medium showed Trx activity with NADPH and Trx reductase using an insulin disulfide reduction assay. Starting from 5 l of serum-free MP6 conditioned medium, the Trx was purified approximately 100,000-fold. After gel electrophoresis banding, the material was analyzed by peptide sequencing and a full length sequence of an 104 amino acid long protein was obtained. This Trx sequence was identical to the previously published sequence of human Trx from HTLV-1 transformed T cells, adult T cell leukemia-derived factor/Trx.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Multidisciplinary mental health teams.

This study surveyed current practice amongst 91 Indian and Australian staff working within multidisciplinary mental health teams, looking at leadership skills, conflict resolution and therapeutic abilities. Length of training was associated with management skills, though these skill were more developed by psychiatric nurses and occupational therapists working in community settings. Hospital settings involved less consensual decision-making than community teams. Psychiatric nurses spent most time in clinical work, and occupational therapists were rated as less skilled in the therapeutic activities assessed than any other profession. Psychiatrists and clinical psychologists undertook most research. The activities assessed in this study could be undertaken by a team comprising psychiatrists, psychiatric nurses and social workers, with clinical psychologists employed where possible, especially for research or service evaluation.

Australia↗
PubMed1994

Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.

The U1 small nuclear ribonucleoprotein particle is essential for splicing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kDa protein (U1-70kDa). We report here that U1-70kDa is specifically cleaved in apoptotic cells, resulting in the generation of a 40-kDa fragment. The kinetics of this cleavage coincided with the appearance of cells with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells that had become detached from the substratum. Although the inhibitor characteristics of the activity cleaving U1-70kDa suggest that interleukin 1 beta-converting enzyme (ICE) might be responsible, the specific ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cleaved by purified ICE in vitro. Further study of this novel cleavage and the enzyme responsible will yield information about proteolytic events that might be central in the mechanism and control of apoptosis.

Apoptosis↗
PubMed1994

Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes.

Systemic lupus erythematosus is a multisystem autoimmune disease in which the autoantibody response targets a variety of autoantigens of diverse subcellular location. We show here that these autoantigens are clustered in two distinct populations of blebs at the surface of apoptotic cells. The population of smaller blebs contains fragmented endoplasmic reticulum (ER) and ribosomes, as well as the ribonucleoprotein, Ro. The larger blebs (apoptotic bodies) contain nucleosomal DNA, Ro, La, and the small nuclear ribonucleoproteins. These autoantigen clusters have in common their proximity to the ER and nuclear membranes, sites of increased generation of reactive oxygen species in apoptotic cells. Oxidative modification at these sites may be a mechanism that unites this diverse group of molecules together as autoantigens.

Animals↗
PubMed1994

Lymphogenous metastasis in the primary carcinoma of the fallopian tube.

The bad prognosis of primary Fallopian tube carcinoma (FTC) is mostly ascribed to early lymphogenous metastasis. Yet, there is a lack of information on the tumor size at which lymph node metastasis must be expected to occur. Our study was therefore designed to correlate the anatomopathologic substratum and the histologic results with the lymph node status. Data were obtained from 21 women who received primary surgery, during which additional total pelvic and para-aortic lymphadenectomy was performed as well. The "surgical" staging was compared to the final clinical staging after histologic inspection of the lymph nodes according to the FIGO classification. Lymph node metastases never occurred as long as the tumor was confined to the tube (stage I). Lymphogenous dissemination set in only after further, local expansion of the tumor, involving the ovaries, the peritoneum, or the uterus (surgical stage II); 3 of the 7 patients of surgical stage II had to be reclassified to stage III because of manifest lymph node metastases. After the onset of intra-abdominal or general metastasis (stage IV), lymph node metastases occurred significantly more often (P = 0.048). Due to the specific lymphatic drainage, lymphogenous metastasis must be expected to spread as far as to the para-aortic region even in the early stages. Highly differentiated tumors (G I) do not disseminate into the lymphatic system, not even in advanced stages, whereas anaplastic tumors (G II and III) metastasize relatively early. As soon as metastasis has occurred, prognosis of life diminishes markedly, but not significantly (49 versus 24 months, P = 0.19). Correct FTC-staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy.

Adolescent↗
PubMed1994

Evaluation of adjuvant therapy after surgery for primary carcinoma of the fallopian tube.

OBJECTIVE: To evaluate the impact of postoperative therapy (chemotherapy vs. irradiation) on overall survival. DESIGN: A nationwide retrospective analysis. SETTING: Hanusch-Krankenhaus, Department of Gynaecology, SUBJECTS: 115 patients with histologically proved primary carcinoma of the Fallopian tube: 49 received six treatment cycles of a cis-platinum regimen (group I), 24 patients were treated by full irradiation using 50 Gray minimum (group II). The two groups had a similar distribution of stage I and II; in the more advanced stages chemotherapy was the predominant method of treatment. RESULTS: The five-year survival rate was 53% for women receiving irradiation as against 27% for those given cis-platinum. If the analysis was restricted to those patients with comparable stage I and stage II lesions, the p-value (0.07) was of borderline significance. There was no advantage in adding abdominal to pelvic irradiation (P = 0.62). CONCLUSIONS: Stage I and stage II carcinoma is probably better treated postoperatively by radiotherapy than chemotherapy. Chemotherapy may have more therapeutic potential in patients with more advanced lesions.

Adult↗
PubMed1994

Primary fallopian tube carcinoma--a retrospective survey of 51 cases. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

OBJECTIVE: To evaluate retrospectively the importance of invasion beyond the basement membrane on overall survival in Fallopian tube carcinoma and its influence on the necessity of postoperative adjuvant therapy (stage 0 vs. stage I). DESIGN: In a nationwide analysis the data of 51 patients were evaluated. The participating departments provided the study center with histologic specimens. A re-staging was done according to the FIGO-classification for Fallopian tube carcinomas. Stage 0 patients received no further postoperative therapy, in stage I patients were divided in 2 groups to evaluate the impact of postoperative adjuvant therapy (chemotherapy vs. irradiation). RESULTS: Patients of stage 0 had a significantly better prognosis than patients of stage I (p = 0.035). Stage I patients treated by irradiation showed a significantly better prognosis than patients treated by chemotherapy (p = 0.017). CONCLUSION: Tumour penetration through the basement membrane causes prognosis to deteriorate significantly (5-year survival rate about 50% in stage I). Postoperative therapy is thus indicated with stage I disease. Irradiation seems to give better results than chemotherapy.

Adenocarcinoma↗
PubMed1994

Microwave thermal balloon angioplasty in the atherosclerotic rabbit.

We evaluated the angiographic and histologic response of the coronary vessels of the atherosclerotic rabbit to microwave thermal balloon angioplasty. Sixteen rabbits with atherosclerosis of the external iliac arteries following a high fat diet and endothelial denudation were treated with either CBA or MBA. Four weeks following angioplasty angiography was repeated, and following the death of the animals, the vessels treated were excised for histologic evaluation. In vessels with MBA with peak temperatures of 85 degrees C there was an increase in luminal diameter immediately postangioplasty, from 1.66 +/- 0.32 mm to 2.54 +/- 0.23 mm (p < 0.05). The diameter at 4 weeks (2.29 +/- 0.74 mm) remained increased compared with the preangioplasty diameter (p < 0.05). With microwave angioplasty at 70 degrees C there was an increase in luminal diameter, from 1.92 +/- 0.37 mm to 2.40 +/- 0.22 mm (p < 0.05) immediately postangioplasty. This increase in diameter was not sustained at 4 weeks (1.86 +/- 0.28 mm). In the vessels treated with CBA there was no significant increase in diameter noted either immediately postangioplasty or at 4 weeks postangioplasty. In the thermally treated vessels, histologic evaluation revealed a loss of lipid-laden cells; it also revealed the formation of a concentric hypocellular fibrotic layer. Microwave thermal balloon angioplasty at 85 degrees C results in enhancement of the immediate and delayed response to angioplasty. Modification of the proliferative response to angioplasty may be accomplished with this modality.

Angioplasty, Balloon↗
PubMed1994

[Conisation in stage Ia cervix cancer].

Between 1975 and 1988, a total of 78 patients suffering from cervical cancer stage Ia were treated by conisation based on a positive smear. According to FIGO, these 78 patients consisted of 53 (67.9%) stage Ia1 and 25 (32.1%) stage Ia2 cases. Complete removal of the tumour by conisation was achieved in 51 patients. In 23 cases (29.5%) the margin of resection was reached by a carcinoma in situ, in 4 cases (5.1%) invasive carcinoma was found. Conisation was not followed by further surgery in 10/51 patients with complete tumour removal. One patient (1/23) with incomplete removal underwent surgery elsewhere. In the other 67/78 patients following hysterectomy, the pathologist diagnosed three cases of cervical cancer, 11 cases of carcinoma in situ and 53 cases (67.9%) without pathological findings. Carcinoma in situ after hysterectomy was found in only 2 cases (4.9%) with primarily free resection margins of the conus. Among the 27 patients with carcinoma in situ or invasive carcinoma reaching the conus margin, 9 cases of carcinoma in situ and 3 invasive carcinomas were diagnosed histologically after hysterectomy and one patient underwent surgery elsewhere. In this study, the value of conisation as single therapy of cervical cancer stage Ia1 and stage Ia2 with good prognosis (depth of infiltration of < 3 mm and no invasion of blood vessels) is discussed and the importance of thorough and exact histological examination is emphasised.

Adult↗
PubMed1994

Assertive community treatment for the seriously mentally ill in suburban Sydney: a programme description and evaluation.

Assertive and intensive community treatment for the seriously mentally ill is becoming a widely accepted approach internationally. This type of service is, however, still relatively new in Australia and New Zealand, and it has rarely been fully integrated into a comprehensive catchment area community and hospital mental health service. This paper has two aims. Firstly, it describes an innovative assertive community mental health service in suburban Sydney. This service was initially provided to 64 clients with a serious mental illness, who had previously experienced repeated hospitalisations and were unable to benefit from existing high quality services. Secondly, it presents the results of the ongoing evaluation of this service. Following the implementation of the service, the number of psychiatric bed days occupied by these clients decreased by 62%; the number of clients admitted decreased, client functioning improved and symptom severity decreased, all to a significant degree.

Activities of Daily Living↗
PubMed1993

The E2A gene product contains two separable and functionally distinct transcription activation domains.

The E2A gene encodes transcription factors of the helix-loop-helix (HLH) family which are implicated in cell-specific transcriptional control in several cell lineages, including pancreatic beta cells. In the present work, we show by deletion mapping of both the E2A protein itself and the Gal4-E2A fusion protein that the protein contains at least two distinct activation domains. One domain (located between amino acids 1 and 153) functions efficiently in a variety of mammalian cell lines. The second domain (located between amino acids 369 and 485) functions preferentially in pancreatic beta cell lines. The latter domain shows a pattern of heptad repeats of leucine residues characteristics of "leucine zipper" transcription factors; site-directed mutagenesis of leucines within this repeat led to substantial reductions in activity. The selective properties of this activation domain may contribute to cell-specific transcription directed by the E2A gene.

Adenoviridae↗
PubMed1993

Survival and mortality patterns of an acquired immunodeficiency syndrome (AIDS) cohort in New York State.

The survival experience and causes of death of acquired immunodeficiency syndrome (AIDS) patients were studied using a cohort of 3,699 AIDS patients in New York State, excluding New York City, whose illness was diagnosed before January 1990 at age 13 years or older. The median length of survival for all cases was 11.5 months, and survival increased over time from 5.3 months pre-1984 to 9.3 months in 1984-1986 and to 13.2 months in 1987-1989. In a Cox proportional hazards model, risk of dying was higher for persons aged 35 years or more at diagnosis and for persons with a diagnosis other than Pneumocystis carinii pneumonia or Kaposi's sarcoma whose illness was diagnosed before 1986. In this AIDS cohort, 2,834 (77 percent) persons died before 1991; 87 percent of the death certificates listed human immunodeficiency virus (HIV)/AIDS or an AIDS indicator disease as one of the multiple causes of death. The finding that 13 percent of the death certificates did not mention AIDS/HIV suggests that use of death certificates alone to count HIV-related deaths would result in an undercount. The recent expansion of the federal AIDS case definition is expected to add HIV-infected persons who die from conditions, such as recurrent pneumonia, that were not included in the earlier definition.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cell-specific expression of helix-loop-helix transcription factors encoded by the E2A gene.

The E2A gene encodes transcription factors of the helix-loop-helix family that are implicated in cell-specific gene expression as part of dimeric complexes that interact with E box enhancer elements. It has previously been shown that transcripts of the E2A gene can be detected in a wide range of cell types. We have now examined expression of the mouse E2A gene at the protein level using polyclonal antisera directed against distinct portions of the E2A protein to probe blots of cellular extracts. A 73 kDa protein was identified by this analysis: this protein is highly enriched in cell lines of B lymphoid origin as compared to pancreatic beta-cells and fibroblast cells. The detection of this protein selectively in extracts of lymphoid cells correlates with the presence of the E box-binding activity LEF1/BCF1 in these cells; this binding activity was previously shown to be efficiently recognized by antiserum directed against E2A gene products. Transfection of cells with full length E2A cDNA leads to appearance of protein co-migrating with the 73 kDa protein on SDS gel electrophoresis and co-migrating with LEF1/BCF1 on mobility shift analysis. Our results are consistent with the view that the DNA-binding activity LEF1/BCF1 is a homodimer of E2A proteins; the selective appearance of this putative cell-specific transcription factor in B lymphoid cells seems to be attributable, at least in part, to the elevated E2A protein concentrations in these cells.

Animals↗
PubMed1993

Locoregionally advanced paranasal sinus carcinoma. Favorable survival with multimodality therapy.

To determine the efficacy of multimodality treatment for stage III and IV, advanced paranasal carcinoma, we have retrospectively reviewed local control rate and disease-free survival in patients treated at the University of Chicago (Ill). Twelve consecutive patients with stage III or IV, newly diagnosed paranasal sinus carcinoma treated between 1984 and 1991 were included in this study. Multimodality therapy was composed of a sequence of fluorouracil-cisplatin-based neoadjuvant chemotherapy (in 12 of 12 patients) followed by standard surgical resection (11 of 12 patients) and radiotherapy (12 of 12 patients, 45 to 73 Gy) with or without concomitant chemotherapy. Eleven patients (92%) are currently alive and free of disease, with a median follow-up of 55 months (range, 13 to 105 months). One patient died of persistent disease. Failure was attributed to incomplete surgical resection. There was only one major irreversible treatment complication (cisplatin ototoxic reaction). Our preliminary data suggest improved local control and survival with multimodality therapy that includes systemic neoadjuvant chemotherapy and standard tumor resection in patients with advanced paranasal sinus carcinoma. These results are superior to the reported 40% survival with bimodal therapy and are better than those achieved in our institution for other head and neck primaries with the same treatment regimens.

Adult↗
PubMed1993

Radical lymphadenectomy in the primary carcinoma of the fallopian tube.

The primary carcinoma of the Fallopian tube is a highly aggressive tumor which can spread by the lymphatic route. The object of the present study was to evaluate the impact of radical pelvic and para-aortic lymphadenectomy on overall survival. Radical lymphadenectomy was performed on twelve patients in addition to hysterectomy and bilateral adnexectomy (group I). Twenty-eight patients subjected only to hysterectomy and adnexectomy formed the control group (group II). On average 47.6 lymph nodes were excised per patient. As long as the carcinoma was limited to adnexa and uterus (stages I and II), no lymph node metastases were found, only in stages III and IV were lymph node metastases detectable. Even though the median survival time of group I was considerably higher than of group II (43 versus 35 months), there was no statistically significant difference between the two groups (P < 0.65). Patients with stage III and stage IV disease had relatively longer median survival times if they had a lymphadenectomy. However, the difference was not statistically significant (P < 0.91). We cannot therefore recommend routine radical lymphadenectomy for primary Fallopian tube carcinoma. Whether or not lymph node dissection would lead to better results from rational selection of patient for adjuvant therapy is not known.

Fallopian Tube Neoplasms↗
PubMed1993

First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer.

Estimation of FGF-3 oncogene amplification in DNA samples extracted from paraffin embedded sections of 136 ovarian cancer samples was carried out by a quantitative PCR method. The aim of this study was to elucidate a possible association of FGF-3 copy numbers with established prognostic factors such as age, histology, FIGO stage, grading, postoperative residual tumour mass, ascites, hormone receptor content and preoperative CA 125 serum levels. In addition, correlation of FGF-3 amplification with overall survival of the patients was assessed. There was a borderline positive correlation between preoperative CA 125 serum levels and the degree of amplification of the FGF-3 gene (P = 0.06). A statistically significant association of FIGO-stage with FGF-3 copy number could be found (P = 0.008). No correlation between FGF-3 amplification and overall survival was noted. The data combine to suggest that FGF-3 is an indicator of aggressiveness of ovarian cancer.

Actuarial Analysis↗