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Biomedical subjects

G Fisher

Publications and source records attributed to G Fisher.

At least 37 records · Page 2Linked to original sources

Nursing management of the patient with bone metastases.

OBJECTIVES: To review the problem of bone metastases and strategies aimed at the management of bone metastases. DATA SOURCES: Review articles, book chapters, research studies, and clinical practice. CONCLUSIONS: As patients survive for longer periods, effective management of bone metastases becomes critical to maintaining or improving quality of life. Controlling pain, preventing fractures and oncologic emergencies, and promoting mobility and function are the outcomes of successful management. IMPLICATIONS FOR NURSING PRACTICE: Use of a clinical algorithm may assist the nurse in identifying bone metastases and managing the clinical sequelae, such as pain.

Bone Neoplasms↗

Analysis of meiotic chromosome pairing in the female mouse using a novel minichromosome.

Analysis of a radiation-induced minichromosome using classical cytogenetic techniques and fluorescence in situ hybridization (FISH) has shown this element to be composed primarily, if not entirely, of repeat sequence DNAs that are common to the ends of all chromosomes in the mouse genome. This novel chromosome has been used to examine further the role of centromeric and telomeric DNA sequences in the initiation of homologous chromosome pairing and synapsis in female germ cells. In pachytene oocytes of a fetus carrying two copies of the minichromosome, it was found that these elements were collocalized, but had not undergone synapsis, in half of the cells analysed. The minichromosomes formed a synaptonemal complex in approximately 14% of oocytes. Overall, therefore, the minichromosomes showed a surprising ability to achieve the first phase of homologous chromosome pairing, i.e. collocalization, despite their dearth of chromosome-specific DNA sequences. It is suggested that this collocalization largely results from the tendency of mouse chromosome ends to form centromeric and telomeric clusters at zygotene. The observations here provide support for the proposition that clustering of chromosome ends in early meiosis fosters pairing interactions and synapsis.

Animals↗

Cumulative risk of second primary cancers in women with index primary cancers of uterine cervix and incidence of lower anogenital tract cancers, Michigan, 1985-1992.

A retrospective cohort study of women with cancers of the lower anogenital tract was derived from the Michigan Tumor Registry records for the years 1985-1992. Incidence rates of invasive cervical, vulvar, vaginal and anal cancers were analyzed with respect to age, race, year of diagnosis, stage at diagnosis, and histopathology. The incidence of metachronous primary cancers following initial primaries of the cervix was also investigated. Anogenital cancers constituted about 4% of all cancers in Michigan women between 1985 and 1992. Age-adjusted incidence rates per 100,000 women per year for each site were found to be as follows: 10.1 (cervix), 1.9 (vulva), 1.0 (vagina), and 0.6 (anus). The incidence rates of women in the United States for cancers in the anogenital region were higher in blacks than in whites, with the exception of vulvar cancer. U.S. blacks were more likely to develop squamous cell carcinomas, but less likely to develop adenocarcinomas of the cervix and vagina when compared to whites. Over the 5- to 8-year follow-up period, 6.5% of the women with index cases of cervical cancer developed second primary cancers. This represented a 40% increase in the risk of incident primary cancers compared to the risk in the general population of Michigan women. The significant occurrence of second primaries of the vagina following index primaries of the cervix suggests a shared etiology, such as infection with human papillomavirus. The incidences of cancers related to smoking, including cancers of the urinary bladder, lung/bronchus, and lower anogenital tract were also increased.

Adolescent↗

Retinoic acid receptor beta regulates growth and differentiation in human pancreatic carcinoma cells.

BACKGROUND & AIMS: Retinoic acid receptor beta (RAR beta) expression is lost or decreased during malignant transformation in human pancreatic adenocarcinoma. The aim of this study was to evaluate the role of RAR beta expression in the propagation of a malignant phenotype in human pancreatic carcinoma cells. METHODS: Overexpression of RAR beta in the human pancreatic carcinoma cell line DAN-G was achieved by selecting stable transfected cell clones. Genomic integration and expression were verified by Southern and Northern blotting and electrophoretic mobility shift assays. Growth was determined by cell number and xenografts transplanted into nude mice. Differentiation was examined by immunohistochemistry. RESULTS: Overexpression of RAR beta in DAN-G cells inhibited cellular proliferation in vitro and in vivo. Furthermore, RAR beta overexpression resulted in induction of cellular differentiation in xenografted tumors as evidenced by increased tumor cell expression of duct cell differentiation markers carcinoembryonic antigen (CEA), CA19-9, and cytokeratin 7. CONCLUSIONS: Decreased expression of RAR beta plays a key role in the maintenance of a malignant phenotype in human pancreatic adenocarcinoma and therefore represents a novel target for experimental strategies in the treatment of pancreatic cancer patients.

Animals↗

Signal amplification in the detection of single-copy DNA and RNA by enzyme-catalyzed deposition (CARD) of the novel fluorescent reporter substrate Cy3.29-tyramide.

We demonstrate that the CAtalyzed Reporter Deposition method (CARD), utilizing the novel fluorescent reporter Cy3.29-tyramide, is successful in the Fluorescent in Situ Hybridization (FISH) detection of RNA and single-copy DNA. Histone 4 expression is detected in RNA extracts of 5-phase, synchronized HeLa cells by dot-blot analysis. Gene expression of histone 4 in HeLa cells is demonstrated by FISH via CARD, utilizing oligonucleotide probes. Fluorescence intensity measurements on CARD-amplified histone 4 RNA detection showed (a) a 25-fold amplification of the signal brightness by biotinylated oligonucleotide probes and (b) a sixfold amplification of the signal brightness by horseradish peroxidase (HRP)-labeled histone 4 probes vs the directly stained control. The sensitivity of the CARD method is demonstrated by the FISH detection of single-copy DNA on human corneal fibroblast and HeLa S5 interphase nuclei. Chromosomal localization of the single copy DNA is demonstrated on HeLa S3 metaphase chromosome spreads.

Avidin↗

Clinical decision making based on radionuclide determined ejection fraction in oncology patients.

UNLABELLED: Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy. A resting LVEF of 50% is usually used as the lower limit of normal values. The decision to change chemotherapy, however, is complex and is affected by many factors, including ejection fraction. METHODS: To determine how LVEF data were used by clinical oncologists in clinical decision making, we performed a retrospective analysis of patients referred for ejection fraction measurements from the hematology/oncology divisionS of Stanford University from March 1992 through March 1995. The records of 565 patients treated with potentially cardiotoxic chemotherapy were evaluated. RESULTS: LVEFs < 50% were found in 153 patients. The charts of patients with reduced ejection fractions were reviewed to determine if the radionuclide measurement resulted in either discontinuation of the cardiotoxic agent or substitution of a less cardiotoxic drug or mode of administration. These specific changes in therapy occurred in only 43 of the 153 (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection fractions < or = 40%. Patients with lower ejection fraction values were more likely to have their therapy changed than those with LVEFs close to normal. Patients with ejection fractions < or = 30 generally had cardiotoxic agents discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not changed, 81% had a normal increase in LVEF with exercise. CONCLUSION: In clinical practice at our institution, ejection fraction < 50% is not used as an absolute contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%, potentially cardiotoxic therapy is most often discontinued or omitted. Radionuclide evidence of cardiac reserve may account for decisions to continue cardiotoxic agents despite ejection fractions < 50% in the majority of patients. Further study will be needed to establish standard criteria. Reserve function, as measured by the change in ejection fraction from rest to stress may be an important parameter used by oncologists to help select patients for continued therapy in spite of a reduced ejection fraction. Our results argue that use of fixed criteria may be too restrictive.

Antineoplastic Agents↗

Bone metastases: Part I--Pathophysiology.

Many cancers (especially breast, prostate, and lung cancers) metastasize to the bone. The most frequent site of bone involvement is the axial skeleton (i.e., cranium, ribs, spine, and pelvis). The sequelae of bone metastases include pain, hypercalcemia, pathologic fractures, and spinal cord compression. As patients survive for longer periods, effective management of bone metastases becomes critical to maintaining or improving quality of life. Controlling pain, preventing fractures and oncologic emergencies, and promoting mobility and function are the outcomes of successful management. Use of a clinical algorithm can assist the nurse in identifying bone metastases and managing the clinical sequelae. Knowledge of the pathophysiology and the ability to assess bone metastases will contribute to the nurse's ability to manage the clinical problems and to improve the quality of life of patients with cancer.

Bone Neoplasms↗

Bone metastases: Part II--Nursing management.

Nurses play a crucial role in identifying bone metastases and managing clinical sequelae, such as pain. Understanding the metastatic process is necessary for delivering effective nursing care. Part I of this article described the pathophysiology and assessment. Part II will provide an overview of the nursing management of the sequelae of bone metastases, including pain, pathologic fractures, spinal cord compression, hypercalcemia, and anemia. Risk factor identification can lead to prevention and early detection of these clinically significant problems. Clinical management of bone metastases will contribute to the nurse's ability to improve the quality of life of patients with cancer.

Bone Neoplasms↗

Cytogenetic and genetic studies of radiation-induced chromosome damage in mouse oocytes. I. Numerical and structural chromosome anomalies in metaphase II oocytes, pre- and post-implantation embryos.

The incidences of X-ray induced numerical and structural chromosome anomalies were screened in a range of developmental stages from metaphase II oocytes through to post-implantation embryos. Following 1 Gy of acute X-rays to immediately preovulatory stage oocytes, the rate of hyperploidy (chromosome gain) was found to be elevated over levels in unirradiated controls, at metaphase II, in 1-cell and 3.5 day pre-implantation embryos but not in 8.5 day post-implantation foetuses. In the latter, however, the frequency of mosiacism was significantly increased. A similar response of an increase in mosaicism but not in hyperploidy in 8.5 day post-implantation embryos was also found after irradiation of dictyate stage oocytes with 4 Gy of acute X-rays. Significantly elevated frequencies of structural chromosome anomalies were present in metaphase II oocytes and pre-implantation embryonic stages, but could not be detected in block-stained chromosome preparations from 8.5 day post-implantation foetuses. However, analysis of chromosome preparations after G-banding showed that almost 14% of 14.5 day foetuses carried a chromosome rearrangement after 1 Gy of X-rays to immediately preovulatory stage oocytes. Overall, our data indicate that the presence of radiation-induced chromosome gains are incompatible with embryonic survival but that a proportion of embryos with structural chromosome damage develop past mid-gestation. These latter embryos are therefore potentially capable of contributing to the genetic burden of the next generation.

Animals↗

Cytogenetic and genetic studies of radiation-induced chromosome damage in mouse oocytes. II. Induced chromosome loss and dominant visible mutations.

The rates of X-ray induced loss of chromosome 19 in mouse oocytes were investigated in 2 experiments using a genetic complementation test. After 1 Gy of acute X-rays to immediately preovulatory stage oocytes, chromosome 19 loss was estimated to have occurred in 1.68% of cells. In comparison, after 4 Gy of acute X-rays to dictyate stage oocytes, the rate was estimated at 1.18%. The slightly higher rate of chromosome loss in the former cell stage after a smaller dose of radiation reflects the known increased radiosensitivity of mouse oocytes in the period shortly before ovulation. Comparison of the observations here for chromosome 19 with published data for chromosome 1 suggests that chromosome length is one of the principal factors in determining the initial rate of induced loss in mouse oocytes. Ten dominant visible mutations were recovered among 1674 offspring following irradiation of preovulatory oocytes, and 8 in 2025 offspring after treatment of dictyate cells. Nine dominant mutations were karyotyped, 5 of these were found to be associated with a visible chromosome rearrangement. The data obtained in the present study show that radiation-induced chromosome anomalies in female germ cells are not all filtered out by prenatal embryonic death but that a proportion has the potential to contribute to the genetic burden of the next generation.

Animals↗

Involvement of D-aspartic acid in the synthesis of testosterone in rat testes.

D-Aspartic acid (D-Asp) is an endogenous amino acid which occurs in many marine and terrestrial animals. In fetal and young rats, this amino acid occurs prevalently in nervous tissue, whereas at sexual maturity it occurs in endocrine glands and above all in pituitary and testes. Here, we have studied if a relationship exists between the presence of D-Asp and the hormonal activity. The following results were obtained: 1) Both D-Asp and testosterone are synthesized in rat testes in two periods of the animal's life: before birth, about the 17th day after fertilization and, after birth, at sexual maturity. 2) Immunocytochemical studies have demonstrated that this enantiomer is localized in Leydig and Sertoli cells. 3) In vivo experiments, consisting of i.p. injection of D-Asp to adult male rats, demonstrated that this amino acid accumulates in pituitary and testis (after 5 h, the accumulation was of 12 and 4-fold over basal values, respectively); simultaneously, luteinizing hormone, testosterone and progesterone significantly increased in the blood (1.6-fold, p < 0.05; 3.0-fold, p < 0.01 and 2.9-fold, p < 0.01, respectively). 4) Finally, in vitro experiments, consisting of the incubation of D-Asp with isolated testes also demonstrated that this amino acid induces the synthesis of testosterone. These results suggest that free D-Asp is involved in the steroidogenesis.

Animals↗

Prospects, problems, and prerequisites for national health examination surveys in developing countries.

Design options for the development of health information systems are evaluated. The health examination survey is found to be an appropriate method for meeting data needs for health planning, program design, and evaluation activities in developing countries. The model proposed is a national cross-sectional prevalence survey employing both interviews and physical examinations to produce a health status profile of a countries population. Examination data are objective, internationally comparable, and not dependent upon reports of clinical encounters in the population. Limitations inherent to health examination surveys are reviewed in reference to their potential in developing countries. Not all countries may be able to conduct health examination surveys; criteria are presented to assist in evaluation of the feasibility of application in specific countries.

Cross-Sectional Studies↗

Induction of apoptosis in mature T cells by tumour necrosis factor.

T-cell receptor-induced apoptosis regulates immune responses and can result from interactions between Fas (Apo1/CD95) and Fas ligand (FasL). Mutations in the genes for Fas and FasL cause disorders resembling human autoimmune diseases in lpr and gld mice, respectively. However, peripheral T-cell deletion takes place in lpr mice, and autoimmune syndromes occur in mouse strains without Fas or FasL defects. Here we show that tumour necrosis factor (TNF) can mediate mature T-cell receptor-induced apoptosis through the p75 TNF receptor. Blockage of both TNF and FasL is required to abrogate T-cell death and TNF mediates the death of most CD8+ T cells, whereas FasL mediates the death of most CD4+ T cells. Our results suggest that autoregulatory apoptosis of the mature T cells can occur by two distinct molecular mechanisms.

Animals↗

D-aspartate in the male and female reproductive system of Octopus vulgaris lam.

Free D-aspartate (D-Asp) has been previously found in the nervous system of Octopus vulgaris (Mollusca: Cepalopoda) and has recently also been found in many endocrine tissues of the rat. The present study examined whether this enantiomer also occurs in the reproductive system and the brain of the octopus. In this mollusk, D-aspartate was present in both the male and the female reproductive systems. In males, it was found at high concentrations in the prostate, vas deferens, Needham's sac, and testis. In females, a high concentration was found in the oviduct, accessory nidamental gland, and ovary. The concentration varied between 0.4 and 2.9 mumol/g wet tissue, which corresponds to a percentage of D-Asp/total D+L-Asp between 7 and 33%. No appreciable quantities of D-Asp were found in the digestive, excretory, circulatory, and muscular systems, indicating that in the octopus this enantiomer may play a role in both the nervous and the reproductive systems.

Animals↗

Autocrine feedback death and the regulation of mature T lymphocyte antigen responses.

Antigen-induced T cell death is an important regulatory mechanism in the peripheral immune system. Evidence suggests that this process depends on T cell growth-inducing lymphokines such as IL-2 and occurs in proportion to the degree of T cell receptor occupancy. Strong T cell receptor stimulation leads to the synthesis of death molecules such as Fas ligand and tumor necrosis factor that cause T cell suicide. We propose that T cell death under these circumstances is the culmination of a feedback control mechanism termed propriocidal regulation or autocrine feedback death that regulates the expansion of specific T cell clones under conditions of high lymphokine and antigen load. In a quasi-stochastic system such as the antigen receptor repertoire, feedback information may be essential for the appropriate regulation of peripheral immune responses. Our understanding of this feedback mechanism affords a means to manipulate antigen-specific T cell death in vivo. The application of this approach to the therapy of T cell-medicated immunological diseases is discussed.

Animals↗