Biomedical subjects

D Higgs

Publications and source records attributed to D Higgs.

15 recordsLinked to original sources

PubMed1996

Determinants of haemoglobin level in steady-state homozygous sickle cell disease.

High total haemoglobin levels in homozygous sickle cell (SS) disease are a risk factor for painful crises, avascular necrosis of the femoral head, proliferative sickle retinopathy, and the acute chest syndrome. Since lowering the haemoglobin level may ameliorate these features, understanding the determinants of total haemoglobin may be of practical importance. A range of possible determinants including red cell characteristics, reticulocytes, serum iron, transferrin saturation, serum ferritin, alpha thalassaemia status, red cell mass and plasma volume, oxygen affinity, red cell survival, transferrin receptor and erythropoietin levels have been measured in 62 patients selected to provide a range of total haemoglobin and fetal haemoglobin levels. There were weak negative associations of haemoglobin with mean cell volume and mean cell haemoglobin concentration, strong negative associations with proportional reticulocyte counts, oxygen affinity, plasma volume, serum transferrin receptors, and erythropoietin levels and strong positive associations with red cell mass. Weighted analysis suggested that the statistically independent determinants of haemoglobin level were alpha thalassaemia, sex, red cell mass/body weight, plasma volume/body weight, fetal haemoglobin, and red cell count. The apparent contributions of red cell survival, P50, reticulocyte count, serum transferrin receptor and erythropoietin levels were explained by the effects of these other variables. The independent determinants as a group explained 91% of the variation in haemoglobin level.

Adult↗

PubMed1994

Helix pomatia agglutinin binding is a useful prognostic indicator in colorectal carcinoma.

BACKGROUND: Most deaths from colorectal carcinoma are due to metastases. A relatively reliable prognostic indicator at surgery to date is the Dukes' stage, but this is a morphologic approach that does not elucidate biochemical changes to explain why cells became metastatic. The binding sites for the lectin from the Roman snail Helix pomatia (HPA) were shown to be good prognostic indicators in breast and gastric cancer, and accordingly, this study was performed to evaluate the use of HPA binding sites as prognostic markers in colorectal carcinoma. METHODS: The histochemically detected expression of HPA binding sites in colorectal carcinomas (n = 130) was increased. The results of the histochemical findings were correlated with patient survival and tumor recurrence. RESULTS: The results indicated that the prognosis for the groups of patients whose colorectal cancer cells binded to HPA in tissue sections was almost as bad as those with Dukes' Stage C disease. CONCLUSION: Because HPA binds to N-acetylgalactosamine, the authors' results indicate that this sugar residue is at least partly involved in the process of human colorectal carcinoma cells metastasizing to regional lymph nodes and possibly also to distant sites.

Acetylgalactosamine↗

PubMed1993

The regulation of human globin gene expression.

The haemopoietic system provides a well-characterized and accessible system for studying the mechanisms of developmental regulation and differentiation in higher eukaryotes. Our current understanding of the steps involved in the early stages of differentiation are poorly understood but a great deal is now known about the mechanisms by which globin expression is regulated in cells committed to the erythroid lineage. Many of the critical cis-acting sequences and some of the important trans-acting factors involved have been identified and current work is focusing on how these interact to produce high levels of tissue-specific and developmentally regulated expression of the human globin genes.

Animals↗

PubMed1993

Transcriptional activation of human zeta 2 globin promoter by the alpha globin regulatory element (HS-40): functional role of specific nuclear factor-DNA complexes.

We studied the functional interaction between human embryonic zeta 2 globin promoter and the alpha globin regulatory element (HS-40) located 40 kb upstream of the zeta 2 globin gene. It was shown by transient expression assay that HS-40 behaved as an authentic enhancer for high-level zeta 2 globin promoter activity in K562 cells, an erythroid cell line of embryonic and/or fetal origin. Although sequences located between -559 and -88 of the zeta 2 globin gene were dispensable for its expression on enhancerless plasmids, they were required for the HS-40 enhancer-mediated activity of the zeta 2 globin promoter. Site-directed mutagenesis demonstrated that this HS-40 enhancer-zeta 2 globin promoter interaction is mediated by the two GATA-1 factor binding motifs located at -230 and -104, respectively. The functional domains of HS-40 were also mapped. Bal 31 deletion mapping data suggested that one GATA-1 motif, one GT motif, and two NF-E2/AP1 motifs together formed the functional core of HS-40 in the erythroid-specific activation of the zeta 2 globin promoter. Site-directed mutagenesis further demonstrated that the enhancer function of one of the two NF-E2/AP1 motifs of HS-40 is mediated through its binding to NF-E2 but not AP1 transcription factor. Finally, we did genomic footprinting of the HS-40 enhancer region in K562 cells, adult nucleated erythroblasts, and different nonerythroid cells. All sequence motifs within the functional core of HS-40, as mapped by transient expression analysis, appeared to bind a nuclear factor(s) in living K562 cells but not in nonerythroid cells. On the other hand, only one of the apparently nonfunctional sequence motifs was bound with factors in vivo. In comparison to K562, nucleated erythroblasts from adult human bone marrow exhibited a similar but nonidentical pattern of nuclear factor binding in vivo at the HS-40 region. These data suggest that transcriptional activation of human embryonic zeta 2 globin gene and the fetal/adult alpha globin genes is mediated by erythroid cell-specific and developmental stage-specific nuclear factor-DNA complexes which form at the enhancer (HS-40) and the globin promoters.

Base Sequence↗

PubMed1991

Knowledge and beliefs about cancer in a socioeconomically disadvantaged population.

Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors.

Consumer Behavior↗

PubMed1991

The haematology of homozygous sickle cell disease after the age of 40 years.

Haematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40-73 years. Cross-sectional analyses in 5-year age bands indicated age-related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age-related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.

Adult↗

PubMed1991

The red cell distribution width in sickle cell disease--is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.

Adolescent↗

PubMed1989

Ifosfamide: a clinical review.

Although ifosfamide first underwent clinical trials 15 years ago, it has largely been ignored by the American oncology community until the last few years. Earlier concerns about dose-limiting hemorrhagic cystitis have been mitigated by the development of effective urothelial protectors such as mesna. Furthermore, ifosfamide is not completely cross-resistant with cyclophosphamide. Ifosfamide has activity in a variety of disseminated refractory solid tumors that do not traditionally respond to conventional alkylating agent therapy, specifically refractory germ cell tumors, soft tissue sarcomas, and malignant lymphomas. The decreased myelosuppression and lack of apparent cross-resistance compared with cyclophosphamide make ifosfamide an ideal drug for inclusion in combination chemotherapy. While clarification of the differences between ifosfamide and cyclophosphamide is ongoing, ifosfamide may eventually replace cyclophosphamide in conventional combination chemotherapy regimens for a variety of solid tumors. At present, it has clear-cut major activity in refractory germ cell tumors and has become an integral component of a curative salvage regimen.

Antineoplastic Agents↗

PubMed1986