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Biomedical subjects

P Nowell

Publications and source records attributed to P Nowell.

At least 19 recordsLinked to original sources
PubMed2001

Protecting sleep quality in later life: a pilot study of bed restriction and sleep hygiene.

We tested two interventions for improving sleep consolidation and depth in normal elderly participants: a modification of sleep-restriction therapy and sleep-hygiene education. Twenty-one elderly participants without sleep disorders were randomized to sleep hygiene plus bed restriction (i.e., restricting time in bed by 30 minutes nightly for one year) or to sleep hygiene alone. Participants in the bed-restriction group showed a median increase in sleep efficiency of 6.1% versus 1.8% in participants receiving sleep hygiene instruction, and an increase in allnight delta EEG power. Self-reported mood on awakening in the morning showed greater improvement over the first eight weeks in the sleep-hygiene condition. The use of sleep hygiene was associated with initial improvement in daytime well-being, whereas bed restriction led to sustained improvements in sleep continuity and sleep depth.

Aged↗
PubMed2000

Disruption of the IFN-gamma cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis.

Recent evidence indicates that the slowly expanding population of CD5+ B cells that characterizes chronic lymphocytic leukemia (CLL) results primarily from defects in responses to cytokines that regulate apoptosis (e.g. I1-4, TGF-beta, IFN-alpha, IFN-gamma). We have now demonstrated not only that the enhanced anti-apoptotic effect of IFN-gamma on these neoplastic B cells is apparently mediated through increased levels of IFN-gamma receptors but also that there are increased numbers of IFN-gamma-expressing CD4 and CD8 T cells in these patients. This is the strongest evidence to date that multiple alterations in the IFN-gamma cytokine network contribute to the pathogenesis of CLL.

Adult↗
PubMed2000

Sleep in neuropsychiatric disorders.

Sleep disorders have been recognized for millennia as a common complication of medical and neurologic disease. Virtually all neuropsychiatric disorders carry with them the potential for disturbances of sleep. When such complications do exist, they are typically associated with decreased quality of life, increased morbidity, and, in some cases, increased mortality rates. The prevalence of major sleep disorders among neurologic patients is high, but the rate of detection and treatment is quite low. The major sleep-related problems in this population can be divided into six areas: insomnia, circadian rhythm (sleep-wake schedule) disorders, hypersomnia, sleep-related breathing disorders, motor disturbances in sleep, and parasomnias. In this brief review, general clinical principles, diagnostic assessment and management guidelines for each of these areas are considered and their specific manifestations in neuropsychiatric disorders identified.

Brain Diseases↗
PubMed1993

Sequential development of Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and myeloid leukemia in a child with type 1 neurofibromatosis: a clinical and cytogenetic case report.

In her 8 1/2 years of life, a girl with neurofibromatosis type 1 (NF1) developed four sequential primary malignant neoplasms: Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and acute myeloid leukemia. The last three tumors were characterized by chromosomal abnormalities non-randomly associated with that particular disease. There was no evidence of germline p53 mutation or of mutation of p53 in the last two tumors. We hypothesize that an unusual mutation of the NF1 gene in this child promoted growth in tissues where the normal or mutated NF-1 gene product is usually silent or growth inhibitory.

Bone Marrow↗
PubMed1991

A clonal CD4-positive T-cell line established from the blood of a patient with Sézary syndrome.

The reported inability to establish long-term T-cell lines from the blood of cutaneous T-cell lymphoma patients with circulating neoplastic T cells has hindered the development of an in vitro system to investigate Sézary syndrome. We have established a rapidly proliferating T-cell line from the peripheral blood of a patient with Sézary syndrome, which expresses a mature helper T-cell phenotype and contains cytogenetic abnormalities and T-cell receptor gene rearrangements identical to those in the patient's blood. The method of establishment and characteristics of this line are described.

Aged↗
PubMed1990

BCL2-mediated tumorigenicity of a human T-lymphoid cell line: synergy with MYC and inhibition by BCL2 antisense.

A gene-transfer approach was used to explore the function of the BCL2 (B-cell lymphoma/leukemia 2) gene in a human T-cell line, Jurkat. Though stable introduction of a BCL2 expression plasmid into Jurkat T cells was by itself insufficient, the combined transfer of BCL2 and MYC genes markedly enhanced the tumorigenicity of these cells in athymic mice. Moreover, a BCL2 antisense expression plasmid ablated tumor formation by Jurkat cells, providing further evidence that this oncogene contributes to the regulation of the in vivo growth of these human T lymphocytes. In addition to their influence on tumor formation, BCL2 sense and antisense expression plasmids increased and decreased, respectively, the in vitro survival of Jurkat T cells in serum-free medium. These observations extend to T cells the finding of synergy of BCL2 with MYC previously reported for B cells and provide evidence that BCL2 can regulate the growth of human T cells.

Animals↗
PubMed1990

Lasers in ophthalmology.

Lasers in ophthalmology have evolved tremendously during the last 3 decades. The laser is a valuable tool for the ophthalmologist today and will continue to be in the future. Currently, through laser technology advancements, vision is being maintained for some patients who would otherwise have severely impaired eye sight because of the lack of appropriate intervention. With the recent advances in excimer laser research, many patients may not have to wear glasses at all. Laser surgery is also minimizing the need for hospitalization and is offering a cost-effective means of treatment for ophthalmologic conditions. Laser technology is indeed revolutionizing ophthalmology.

Cataract Extraction↗
PubMed1987

Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines.

Eight permanent cell lines were established from cells of 50 consecutive patients with childhood acute leukemia. Three cell lines required growth factor-containing conditioned media. Analysis using blocking antisera and recombinant granulocytic macrophage (GM) colony-stimulating factor (CSF) identified GM-CSF as a growth factor required to establish the latter three cell lines and necessary for their continuous proliferation in chemically defined medium. Two of the GM-CSF-dependent cell lines were derived from patients with undifferentiated T- and a biphenotypic B-myelomonocytic leukemia, which suggests that GM-CSF might maintain proliferation of leukemias originating from immature progenitor cells. Cytogenetic analysis indicated that all established leukemic cell lines were aneuploid, with six lines containing chromosomal alterations related to those observed in the leukemic cells of the patient. Two patients did not have an abnormal clone identified in the marrow but did yield an aneuploid cell line. These studies indicate that GM-CSF-dependent leukemic cell lines can be established in a fraction of childhood leukemia. These cell lines lend themselves to studies aimed at the evaluation in vitro of the role of growth factors in controlling proliferation and differentiation of leukemic cells.

Acute Disease↗
PubMed1986

Disappearance of cytogenetic abnormalities and clinical remission during therapy with 13-cis-retinoic acid in a patient with myelodysplastic syndrome: inhibition of growth of the patient's malignant monocytoid clone.

Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.

Anemia↗
PubMed1985

Preleukemia and leukemia with 12p- and 19q+ chromosome alterations following Alkeran therapy.

Among 20 patients with acute nonlymphocytic leukemia or dysmyelopoietic preleukemia secondary to Alkeran therapy for another tumor, four had a del(12)(p11-p12) and four had a translocation to 19q13 among multiple karyotypic alterations in their neoplastic hematopoetic clones. It is suggested that these two cytogenetic abnormalities may occur nonrandomly in such hemic disorders and may play a limited role in their pathogenesis.

Chromosome Deletion↗
PubMed1985

A 2p;11q chromosome translocation in dysmyelopoietic preleukemia.

Three patients with dysmyelopoietic preleukemia had a marrow clone with translocation t(2;11)(p21;q23) as the only chromosome change. In one patient, the cytogenetically altered cells disappeared following treatment with 13-cis-retinoic acid. Although these patients did not constitute a homogeneous clinical subgroup, the 2p;11q translocation should probably be added to the short list of nonrandom karyotypic alterations involving 11q23 that have been described in various hematopoietic disorders.

Aged↗
PubMed1985

Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma.

Epidermal growth factor (EGF) receptor is expressed selectively by human melanoma cells which show the presence of an extra copy of chromosome 7. None of the cells of benign pigmented lesions (nevi) or radial growth phase (nonmetastatic) primary melanoma expressed EGF receptor and none of these cells showed an extra copy of chromosome 7. The results indicate that a single extra dose of a gene (for EGF receptor) may provide a selective advantage to cells in the late stages of tumorigenesis.

Antibodies, Monoclonal↗
PubMed1985

Characteristics of cultured human melanocytes isolated from different stages of tumor progression.

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.

Antibodies, Monoclonal↗
PubMed1984

Two adult siblings with thrombocytopenia and a familial 13;14 translocation.

A woman with thrombocytopenia that progressed to aplastic anemia, and her brother, who had persistent thrombocytopenia, both had a constitutional t(13;14) translocation. Six other family members, in three generations, had the same translocation, but no hematologic disorder. There was evidence suggestive of increased chromosomal fragility in lymphocyte cultures from two members of the kindred, but not in the two patients. The findings support a postulated association between the t(13;14) and hematologic disorders, but whether the mechanism involves an inherited defect in chromosomal stability is unproved.

Chromosome Fragility↗
PubMed1984

Progressive preleukemia with a chromosomally abnormal clone in a kindred with the Estren-Dameshek variant of Fanconi's anemia.

One of two sisters with hypoplastic anemia and increased chromosomal fragility, but no clinical stigmata of Fanconi's anemia (FA), progressed to preleukemia (with a clone of chromosomally abnormal cells in the bone marrow), and then to acute nonlymphocytic leukemia. The findings indicate that constitutional genetic instability can lead to karyotypically aberrant neoplastic clones in the Estren-Dameshek variant of FA as well as in the more typical chromosomal fragility syndromes.

Adolescent↗
PubMed1983

Cytogenetics of childhood preleukemia.

Chromosome studies were done on ten children with childhood preleukemia characterized by anemia, thrombocytopenia, blasts in the circulation, and hypercellular marrow with excess blasts. The syndrome was clinically similar to adult preleukemia (myelodysplastic disorder). A chromosomally abnormal clone was found in the marrow in five patients: three with monosomy 7; one with a chromosome No. 21 replaced by two isochromosomes for 21q; and one with multiple alterations including an extra, abnormal chromosome No. 7. It was not apparent that a karyotypic change indicated a worse prognosis. The observed chromosome abnormalities appeared to overlap less with those in acute nonlymphocytic leukemia occurring de novo than is the case in adults, perhaps reflecting differing contributions of genetic and environmental factors to the pathogenesis of the disease at different ages.

Acute Disease↗