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Biomedical subjects

P Russell

Publications and source records attributed to P Russell.

At least 271 records · Page 15Linked to original sources
PubMed1989

The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors.

Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being both ER+ and PR+. There was no significant relationship between receptor expression and stage, grade, or histological subtype. Thirteen percent of diploid tumors were receptor negative in contrast to 38% of aneuploid tumors (P less than 0.01). There was no significant association between ER status and ploidy, but 60% of diploid tumors were PR+ in contrast to 33% of aneuploid tumors (P less than 0.02). Eleven percent of tumors overall were both ER rich and PR rich and comprised 23% of diploid and 5% of aneuploid tumors (P less than 0.01). Receptor-negative tumors had a median S phase of 18.8% which was significantly higher than the median S phase of 12% in receptor-positive tumors (P less than 0.02). A similar analysis was also performed on specimens from 9 patients with borderline epithelial ovarian tumors and 12 with benign epithelial ovarian tumors. Up to 50% of benign and borderline epithelial tumors had measurable receptors, but all were diploid with a relatively low S phase fraction. The functional significance of steroid receptor expression in ovarian cancer is unclear, but the association with ploidy and proliferative activity particularly in patients with malignant ovarian tumors may allow better identification of prognostic subsets and aid in selection of patients for hormonal therapy.

Adult↗
PubMed1989

A comparative study of proliferating (borderline) and invasive epithelial ovarian tumours in young women.

A series of 18 patients with proliferating or borderline ovarian tumours and 18 with invasive ovarian tumours is discussed. Proliferating tumours occurred at a younger mean age than invasive disease, and presented at an earlier stage, both contributing factors to their more favourable outlook. Histopathological assessment revealed that the majority of both proliferating and invasive tumours were of serous origin. Mucinous cell type occurred less often as did the endometrioid and clear cell types. The management of the proliferating tumours involved 'radical' surgical procedures in 11 of 18 (61.6%) patients. Only 7 patients (38.8%) had conservative surgical procedures performed. Six patients (33%) had adjuvant chemotherapy while 2 (11%) also underwent abdominopelvic irradiation. All patients with invasive disease had radical surgery and adjuvant chemotherapy and 2 also received abdominopelvic irradiation. The fact that epithelial malignancies of the ovary do occur in younger women needs to be remembered by gynaecologists contemplating surgical procedures on younger patients with adnexal masses. Proliferating or borderline tumours tend to occur more frequently in the younger age groups, and contrary to the implication of their name, they are associated with significant morbidity and mortality.

Adolescent↗
PubMed1989

Blepharophimosis plus ovarian failure: a likely candidate for a contiguous gene syndrome.

We describe four females from three families with blepharophimosis, epicanthus inversus, and ptosis who were found to have premature ovarian failure. In two families the inheritance was autosomal dominant and in one it was a new mutation. Two females had, in addition, dysmorphic facial features which have been described in other cases. We suggest that the aetiology of the blepharophimosis ovarian failure syndrome is a contiguous gene syndrome.

Adult↗
PubMed1988

Alteration of a developmentally regulated, heat-stable polypeptide in the lens of the Philly mouse. Implications for cataract formation.

The beta-crystallin basic principal polypeptide (beta Bp) appears to be altered in the lens of the Philly mouse and may be the main defect in this hereditary cataract. Northern blot analysis showed that an mRNA encoding for beta Bp is present in the Philly mouse lens, but normal beta Bp could not be detected. Instead, a different protein related to beta Bp has been observed. Western blot analysis with antibodies against specific beta Bp peptide sequences showed that the Philly protein shares the same amino-terminal residue as beta Bp but lacks a part of the carboxyl-terminal half of normal beta Bp. The altered protein is slightly smaller than beta Bp and has a more acidic isoelectric point by two-dimensional gel electrophoresis. It also lacks the property of heat stability characteristic of normal beta Bp. The mapping of the alteration in beta Bp may give insight into the nature of the heat stability of this protein as well as some indication of the structural components that are necessary to maintain optical clarity in the lens.

Animals↗
PubMed1988

The oxidative modification of lens proteins.

In summary, in vitro oxidation of lens crystallins mimics many of the post-translational modifications observed with age and in cataracts These results lend further support to earlier proposals that oxidation is a key factor in cataract formation. The extent to which ascorbate contributes to the oxidation reactions in vivo is not known. In addition to the data presented here that ascorbate can produce these effects in vitro, other observations support the possibility that under certain conditions ascorbate may be involved in the generation of reactive oxygen species in the lens. Using electron spin resonance the ascorbyl radical can be detected early in nuclear cataract formation, and there appears to be a decrease in total ascorbic acid (reduced and oxidized), suggesting further oxidation of ascorbate. Iron and copper are both present in mammalian lenses, and there are reports of increased copper levels in the lens with age and in cataracts. Increased metal ion concentrations would facilitate these oxidative processes.

Aged↗
PubMed1988

Development and characterization of a human cell line from an ovarian mixed Müllerian tumor (carcinosarcoma).

A cell line derived from a human ovarian carcinosarcoma was established in tissue culture and in nude mice. Two sublines, LDF and HDF, separated by discontinuous density centrifugation were also established from the parent line JoN. The cloning efficiency of the JoN line was 21%. Morphologic features of adenocarcinoma cells characteristic of the parent JoN cells were retained in the sublines and clones; all lines showed the same karyotype and DNA content (pseudodiploid and pseudotetraploid). Keratin, as demonstrated immunohistochemically, was strongly expressed in the parent line JoN and the xenograft tumor, but not at all in the LDF sublines and only moderately in the HDF sublines. Vimentin, however, was expressed in neither the parent line JoN nor the xenograft tumor, but was present in both sublines. Transglutaminase and plasminogen activator activity was high in the parent line JoN. Neither, sublines nor clones showed the same high enzyme activity as the parent line. It is concluded that this human tumor line JoN is comprised of epithelial cells, capable of multidirectional differentiation.

Animals↗
PubMed1988

Ectopic hormone production by a prostatic small cell carcinoma xenograft line.

The xenograft line, UCRU-PR-2, has been characterized further. Established from a primary human undifferentiated small cell carcinoma of the prostate, it has been maintained as a stable xenograft line in nude mice and is currently in passage 9. The tumor has maintained the features of small cell undifferentiated carcinoma but shows epithelial as well as neuroendocrine characteristics. In this paper, we describe synthesis and secretion of peptide hormones, ACTH, beta-endorphin and somatostatin in vivo and ACTH and beta-endorphin in vitro by the tumor, UCRU-PR-2. This suggests that the gene for proopiomelanocortin is expressed and that processing of the molecule occurs. This line may yield insights into the histogenesis of the subtypes of prostate cancer, and also aid studies of regulation of ectopic hormone production.

Adrenocorticotropic Hormone↗
PubMed1988

An association among blepharophimosis, resistant ovary syndrome, and true premature menopause.

Four cases are described of a very rare association among blepharophimosis, resistant ovary syndrome, and true premature menopause. Plasma levels of follicle-stimulating hormone and luteinizing hormone were significantly elevated and estradiol significantly decreased in all four cases. Ovarian biopsies demonstrated large numbers of unstimulated primordial follicles in three cases and no follicles in one case. Two of the four women were sisters, with the older having true premature menopause and the younger having resistant ovary syndrome. The explanation for the association of blepharophimosis with primary ovarian dysfunction is unknown, but the possibility of a microdeletion of genetic material containing two geographically associated but independent genes could not be confirmed or excluded by high-resolution chromosome banding. All families affected by the autosomal dominant condition of blepharophimosis should be counseled about the high incidence of ovarian dysfunction and female infertility, at least in one form of the syndrome.

Adult↗
PubMed1988

Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer.

The prognostic value of cellular DNA content in ovarian cancer (malignant common epithelial tumors) was investigated by flow cytometric analysis of paraffin-embedded tumor blocks from 128 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian cancer entered in a prospective clinical trial of combination v sequential therapy with chlorambucil and cisplatin. Seventy-three percent of tumors were aneuploid and 27% were diploid. Multivariate analysis using a Cox model showed that cellular DNA content (P less than .001) and FIGO stage (P less than .02) were the only significant independent prognostic variables. The median survival was 13 months for patients with aneuploid tumors and 60 months for patients with diploid tumors (P less than .0001). Further analysis indicated that the good prognosis associated with diploid tumors was limited to patients with stage III disease, all patients with stage IV (spread beyond the peritoneal cavity or liver metastases) disease having a poor prognosis irrespective of ploidy. On pathological review, nine borderline ovarian tumors (of low malignant potential) were identified, and seven of these were diploid. These tumors have an unusually favorable prognosis, despite apparent dissemination within the peritoneal cavity, a paradox which is often difficult to explain using conventional histological criteria. Although the vast majority of tumors in this study (93%) were classified as invasive epithelial ovarian cancers, it is possible that some of the patients with stage III diploid tumors may have had malignancies that were predominantly of low malignant potential, thus accounting in part for the prognostic significance of DNA content. By incorporating flow cytometric DNA analysis with careful histopathological assessment, it may be possible to better identify patients with an inherently good prognosis. This assumes particular importance, as the relatively favorable prognosis of patients with stage III diploid ovarian tumors appears to be independent of the type of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

An evaluation of CA125, CA1 and peanut lectin immunoreactivity in epithelial ovarian neoplasms: correlation with histopathological features, prognostic variables and patient outcome.

The ability to produce monoclonal antibodies to tumour associated antigens, together with advances in immunocytochemistry, provide the potential for establishing a new functional classification of human tumours. This approach was used to investigate whether the expression of CA125, CA1 and the Thomsen-Friedenreich antigens reflected the biological behaviour of ovarian tumours and, if so, had a potential role in the clinico-pathological assessment of ovarian neoplasms. Expression of these antigens was assessed in benign, borderline and malignant ovarian epithelial tumours and attempts were made to determine if there was any correlation between immunoreactivity and tumour grade, histological subtype, FIGO Stage, tumour ploidy or patient outcome. There was no evidence that expression of these antigens had clinical significance, although it is possible that reactivity with antibody OC125 might identify patients in whom CA125 antigen levels in the sera could be used as a marker to monitor disease progress.

Antibodies↗
PubMed1988

The EDTA extractable protein is glycosylated in the bovine lens.

The EDTA extractable protein (EEP) can be prepared from the bovine lens using sonication; however, urea washing of the membrane fraction was essential in decreasing the non-specific binding of the crystallins to the EEP fraction. Both the 32 and the 35 kilodalton (kD) proteins from EEP were shown to be glycoconjugates using periodate labelling. The EEP from the lens bound a variety of lectins at both 32 and 35 kD. The binding of the lectins suggested that EEP is composed of proteins having galactose or N-acetylgalactosamine groups as well as fucose residues. The glycosylation of EEP adds another possible regulatory step for the control of these calcium binding proteins in the lens.

Animals↗
PubMed1987

Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.

Fission yeast wee1- mutants initiate mitosis at half the cell size of wild type. The wee1+ activity is required to prevent lethal premature mitosis in cells that overproduce the mitotic inducer cdc25+. This lethal phenotype was used to clone wee1+ by complementation. When wee1+ expression is increased, mitosis is delayed until cells grow to a larger size. Thus wee1+ functions as a dose-dependent inhibitor of mitosis, the first such element to be specifically identified and cloned. The carboxy-terminal region of the predicted 112 kd wee1+ protein contains protein kinase consensus sequences, suggesting that negative regulation of mitosis involves protein phosphorylation. Genetic evidence indicates that wee1+ and cdc25+ compete in a control system regulating the cdc2+ protein kinase, which is required for mitotic initiation.

Amino Acid Sequence↗
PubMed1987

The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis.

The newly discovered fission yeast mitotic control element nim1+ (new inducer of mitosis) is the first dose-dependent mitotic inducer identified as a protein kinase homolog. Increased nim1+ expression rescues mutants lacking the mitotic inducer cdc25+ and advances cells into mitosis at a reduced cell size; loss of nim1+ delays mitosis until cells have grown to a larger size. The nim1+ gene potentially encodes a 50 kd protein that contains the consensus sequences of protein kinases. Genetic evidence indicates that nim1+ is a negative regulator of the wee1+ mitotic inhibitor, another protein kinase homolog. The combined mitotic induction activities of nim1+ and cdc25+ counteract the wee1+ mitotic inhibitor in a regulatory network that appears also to involve the cdc2+ protein kinase, which is required for mitosis.

Alleles↗
PubMed1987

Xenografted small cell undifferentiated cancer of prostate: possible common origin with prostatic adenocarcinoma.

The first xenograft line of small cell undifferentiated carcinoma of the prostate (UCRU-PR-2) has been established and characterized. The donor tumor and the xenograft share the common morphological and ultrastructural features of small cell undifferentiated carcinoma (including neurosecretory granules) but also elaborate epithelial membrane antigen and carcinoembryonic antigen, in addition to neurone-specific enolase. The line expresses a diploid DNA complement. Androgen and estrogen receptors are not expressed, although prostatic acid phosphatase is present in sera from tumor-bearing mice in low levels. From these studies, we postulate a possible common stem cell origin for adenocarcinoma and small cell undifferentiated carcinoma of the prostate; further studies of a cell line derived from this tumor may clarify the issue.

Acid Phosphatase↗
PubMed1987

Cytogenetic findings in cell lines derived from four ovarian carcinomas.

Six cell lines, established from four primary ovarian carcinomas were examined cytogenetically. The lines varied greatly in their chromosome complement. All cells from the lines were aneuploid, although one cell line contained two populations having a pseudodiploid and a pseudotetraploid modal chromosome number. Every chromosome group was involved with loss and gain of chromosomes, but some individual chromosomes were more prone to aneuploidy than others. Chromosome #6 was the most stable throughout. Structural changes gave rise to many marker chromosomes. Although most markers were random and the majority unidentifiable, some abnormalities of clonal origin were found. Deletions especially of chromosome #1, were the most common change. Further sequential studies may elicit the origin, stability, and timing of the chromosome abnormalities.

Adenocarcinoma↗
PubMed1987

Aging effects of vitamin C on a human lens protein produced in vitro.

Human lens gamma-crystallin obtained from the expression of a gene construct stably integrated into mouse L cells was incubated with ascorbate in the presence of iron and oxygen. The resulting oxidation of the gamma-crystallin led to more acidic species of this protein. These alterations were similar to the changes seen with aging in the human lens. The results suggest that oxidation of lens crystallins may be responsible for the changes seen on aging and cataract development and that ascorbate may contribute to these alterations.

Aging↗
PubMed1987

Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress.

Antineoplastic Combined Chemotherapy Protocols↗