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Biomedical subjects

F Hall

Publications and source records attributed to F Hall.

At least 19 recordsLinked to original sources

A randomized trial of three iron dextran infusion methods for anemia in EPO-treated dialysis patients.

Forty-three hemodialysis patients receiving recombinant erythropoietin (rHuEPO, epoietin alpha) were randomized to receive intravenous iron dextran as a total-dose infusion, 500-mg infusion to total dose, or 100-mg bolus to total dose, in each case during the dialysis procedure. The dose of iron dextran was calculated from the patient's existing hemoglobin to achieve a desired hemoglobin. Patients were eligible to receive intravenous iron dextran if they had a serum ferritin of < or = 100 ng/mL or a serum ferritin of 100 to 200 ng/mL, along with a transferrin saturation of < or = 19%. Patients were excluded if they had prior therapy with iron dextran, aluminum intoxication, or transfusion during the study. The time to the maximum hemoglobin, acute adverse reactions, and delayed adverse reactions were analyzed statistically, and no differences were seen in any of the three groups. Total-dose intravenous iron dextran infusion is safe, convenient, less expensive, and as efficacious as divided-dose infusions.

Anemia

Multiple T cell expansions are found in the blood and synovial fluid of patients with reactive arthritis.

OBJECTIVE: To look for evidence of T lymphocyte expansions in the blood and synovial fluid (SF) of patients with reactive arthritis (ReA). METHODS: Paired peripheral blood and synovial samples from 10 patients with ReA were studied by dual color flow cytometry using T cell receptor (TCR) V beta specific and CD4 or CD8 specific antibodies. Two synovial CD8 expansions were studied by 3 color flow cytometry. Peripheral blood samples from 13 healthy, age matched individuals were studied as controls. RESULTS: Statistically significant expansions were observed in all patients, occurring in blood and SF CD4 and CD8 compartments, but were most common in the synovial CD8 compartment. Expansions studied in further detail displayed an activated "memory" phenotype. A synovial BV22S1/CD8 expansion was seen in 5/6 patients with sexually acquired ReA. CONCLUSION: Multiple T lymphocyte expansions are found in both the blood and SF of patients with ReA. Expansions were most commonly found in the synovial CD8 compartment, where they appeared to express both activation and memory markers. This indicates that T lymphocytes (and in particular cytotoxic T cells) may play a pathogenic role in ReA. These findings are consistent with either an antigen or a superantigen driven response.

Adolescent

Enteroclysis.

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Enema

Characterization of protein kinases involved in dentinogenesis.

Protein phosphorylation and dephosphorylation control many different cell functions as well as responses to internal and external signals. It has also been shown that highly phosphorylated acidic proteins have an important role in matrix mediated biomineralization, perhaps functioning as nucleators for crystal formation. Dentine phosphoprotein (DPP) is one of such proteins which is exclusively synthesized by the odontoblast cells and therefore a likely candidate to play a significant role in normal and abnormal dentine biomineralization. These studies are directed at characterizing the protein kinases involved in dentinogenesis and in particular the enzyme(s) responsible for DPP phosphorylation. In this report we present data which indicate that there are several different types of kinases in the odontoblast-enriched dental papilla mesenchyme (DPM), some of which can phosphorylate DPP, such as casein kinase I and II. However, a different DPP-kinase activity was identified. This enzyme(s) appears to be different from other reported kinases, and it is the only kinase that can phosphorylate both phosphorylated DPP and enzymatically dephosphorylated DPP.

Acid Phosphatase

Identification of a human epidermal growth factor receptor-associated protein kinase as a new member of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase family.

A putative mitogen-activated protein kinase (MAPK) has recently been identified, which potentially phosphorylates the human epidermal growth factor (EGF) receptor at a physiological site (Thr-669) and is distinguished from other MAPKs/extracellular signal-regulated protein kinases (ERKs) on the basis of chromatographic, immunological, and kinetic data. Here we report that this newly discovered MAPK is physically associated with the EGF receptor in A431 cells and with the related receptor/tyrosine kinase HER2 (encoded by c-neu) in enzyme preparations obtained from Wilm's tumors. This human EGF receptor-associated kinase is characterized as a 40-kDa Thr-669 kinase that exists in a high molecular mass complex with the respective growth factor receptor. EGF treatment of A431 cells stimulates the tyrosine phosphorylation of p40 and increases Thr-669 kinase activity in p40-containing fractions. The 40-kDa kinase is recognized by affinity-purified polyclonal antibodies directed against the sea star p44mpk and a Pan-ERK antibody directed against the conserved subdomain VIII of MAPKs/ERKs, but is not recognized by antibodies selective for the rat p44erk1 and/or the p42mapk/erk2 isoforms, thus identifying the EGF receptor-associated kinase as a novel MAPK that may regulate receptor function in vivo.

Amino Acid Sequence

Age and sleep modify finger temperature responses to facial cooling.

BACKGROUND: The increased incidence of hypothermia with age suggests that healthy 80-year-olds might show impaired responsivity to transient, localized thermal stimulation. Such a deficit might be particularly clear during sleep, when behavioral thermoregulation is less likely. METHODS: We examined finger temperature cooling in response to local cooling of the face--a response presumed to be centrally mediated. Nineteen healthy 80-year-olds (12 female) and twenty-seven 20-year-olds (10 female) were exposed to repetitive 20-minute cooling and rewarming cycles across a night of sleep deprivation and a night of sleep occurring three nights later. We sought to determine whether thermal responsivity was altered by age and sleep, but by design avoided inducing core temperature hypothermia. RESULTS: In response to facial cooling during sleep deprivation, finger temperature decreased significantly more in the young than in old. This suggested relatively greater heat retention in the young. During non-REM sleep the thermal responsivity of both groups decreased and age-related differences were no longer present. Changes in core temperature induced by the stimulation were minimal. CONCLUSIONS: The results suggest that the capability of retaining heat via peripheral vasoconstriction while awake decreases with age. Despite this vulnerability, responsivity during non-REM sleep as well as average core temperature were comparable between age groups.

Adult

G1 expression and multistage dynamics of cyclin A in human osteosarcoma cells.

Cyclin A was initially characterized as a 'mitotic cyclin', believed to function exclusively at the G2-to-M phase transition; however, recent studies have provided compelling evidence that cyclin A additionally functions earlier in the mammalian somatic cell cycle as a putative 'S-phase-promoting factor'. Moreover, numerous inconsistencies have arisen concerning the temporal induction, subcellular localization, subunit configuration, covalent modification and proteolytic destruction of cyclin A, as well as the physiological function of the cyclin A-associated protein kinase complexes. Utilizing precisely synchronized human MG-63 osteosarcoma cells, the present study demonstrates that cyclin A mRNA and protein are clearly expressed in late G1 prior to S-phase entry, as is cyclin A-associated kinase activity and concomitant phosphorylation of the Rb protein. A series of monospecific cyclin A antibodies were generated and utilized to confirm that multiple covalent modifications of cyclin A occur during the course of the cell cycle, and to characterize the subcellular dynamics in additional detail. Pharmacological blockade with mimosine was utilized to further delineate cyclin A expression and to distinguish the temporal induction from the mechanisms of enzyme activation. Subcellular fractionation and immunocytochemical staining localized nascent cyclin A to the cytoplasm, and revealed a distinct translocation to the nucleus during the G1-to-S phase transition. The results of these studies support a multistage model of cyclin A metabolism and enzyme activation.

Amino Acid Sequence

Protein kinases in dentinogenesis.

Protein modifications such as phosphorylation and dephosphorylation are known to control several cell functions including regulation of the cell cycle, signal transduction and enzyme activation/inactivation. Bone and dentin contain highly phosphorylated anionic proteins that appear to be involved in the regulation of mineralization. This study was designed to identify and characterize the enzyme(s) responsible for phosphorylation (kinases) of dentin phosphoprotein (DPP) during dentinogenesis. DPP-protein kinase activity was demonstrated in a crude homogenate of dental pulp and odontoblast cells. In parallel studies, oligonucleotides to conserved amino acid sequences present in the active site of kinases were constructed and used to screen a lambda-gt11 tooth organ cDNA library. Several cDNA clones were isolated, the size of the insert determined by PCR (polymerase chain reaction) amplification, and in situ hybridization was used to determine cellular localization during tooth organ development. Preliminary evidence provides additional molecular determinants involved with candidate kinases responsible for DPP phosphorylation and dentinogenesis.

Animals

Predicting mortality in mixed depression and dementia using EEG sleep variables.

The authors report a study of electroencephalographic (EEG) sleep predictors of two-year mortality in 26 elderly patients with mixed symptoms of depression and cognitive impairment. Patients who had died by two-year follow-up were characterized by significantly longer rapid eye movement (REM) sleep latencies at baseline, less robust REM sleep rebound following all-night sleep deprivation, and baseline apnea-hypopnea indexes greater than 3. Logistic regression analysis using the apnea-hypopnea index value and REM latency correctly predicted 77% of survivors and non-survivors. Survival time following initial measurements was significantly correlated with REM sleep time (r = 0.78, p less than .02) and duration of first REM sleep period (r = 0.75, p less than .02). The authors speculate that changes in these predictor variables may indicate impairment in the cholinergic control of cognitive function, REM sleep, and respiratory function.

Aged

Photoperiodic modulation of cephalic melatonin in planarians.

Endogenous melatonin was detected by high-performance liquid chromatography (HPLC) with electrochemical detection (EC) in the head of the planarian Dugesia dorotocephala. The identity of this elution peak was further confirmed by radioimmunoassay. In groups of planarians adapted to either normal or reversed photoperiods, the melatonin levels were always higher in those heads collected in the dark period than in those collected in the light period. This indicates that primitive animals such as planarians have already evolved a melatonin-metabolizing system that is photically driven in a manner suggestive of the way melatonin synthesis is influenced by light and dark cycles in vertebrates.

Animals

Neoplastic transformation in the planarian: I. Cocarcinogenesis and histopathology.

Although several investigators have reported that exposure to mammalian carcinogens induces abnormal tumorlike growths and teratogenic remodeling in planarians, there is no general agreement that these, or comparable responses in any other invertebrates, model mammalian carcinogenesis. To investigate this question, freshwater planarians of the species Dugesia dorotocephala were exposed to culture water containing an initiator and a promoter, either alone or in combination. Cadmium, a potent carcinogen, was used as an initiator in the protocol. Treatment with sublethal concentrations of cadmium sulfate produced a benign, but persistent, tumor in a small percentage of the planarians. The addition of 12-O-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester and well-known promoter, to the cadmium-containing solutions resulted in the induction of a progressive, potentially lethal, transplantable tumor in a large proportion of the treated flatworms. Light and electron microscopy revealed this particular tumor to be composed both of immature cells and of a single mature cell type: newly differentiated, but transformed, reticular cells. Further examination of the infiltrating tissue formations elucidated the profile of differentiation, from a population of mitotically active transformed stem cells through the transitional stages in the associated reticuloma. These results suggest that 1) the freshwater planarian displays the major phenomenology of mammalian cocarcinogenesis and that 2) the planarian reticuloma models several important features of a neoplastic stem cell disease.

Animals

Neoplastic transformation in the planarian: II. Ultrastructure of malignant reticuloma.

Cadmium and phorbol ester induced tumorigenesis in the planarian, Dugesia dorotocephala, develops as a cocarcinogenic process involving initiation and promotion in the progression of neoplastic disease. Treatment of intact planarians with sublethal concentrations of cadmium sulfate and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced a type of infiltrating tumor that proved to be potentially lethal. Surgical transplantation of such tumorous tissues into otherwise healthy planarians resulted in the same histopathological progression to lethality, which confirmed the metastatic nature of the neoplasia. Electron microscopic studies revealed that both the chemically-induced and the transplantation-based tumors involved, exclusively, the proliferation and differentiation of abnormal reticular cells, referred to as reticuloma cells. Reticular cells normally are ameboid, phagocytic, and are thought to provide the planarian with a phylogenetic predecessor of an immune surveillance system. A considerable incidence of mitosis was observed within the tumor areas; and the sequence of differentiation, from transformed stem cells to mature but nonfunctional reticuloma cells, was elucidated. This profile of differentiation supports the concept of cellular derivation via stem cell dynamics as opposed to dedifferentiation. A variety of ultrastructural abnormalities were characterized: several of which tend to substantiate the anaplastic quality of the reticuloma, while others are more specifically diagnostic for malignancy. These findings further extend the potential usefulness of the planarian malignant reticuloma as a model system for the study of neoplastic stem cell diseases.

Animals

Determination of bovine retinal melatonin with HPLC-EC.

UNLABELLED: Bovine retinae, devoid of pigment epithelium, were assayed for endogenous melatonin using high-performance liquid chromatography with electrochemical detection (HPLC-EC). A method of extracting the more polar biogenic amines and metabolites was employed, allowing for direct injection of retinal supernatants into the chromatographic column. THE RESULTS: 1) confirm the presence of melatonin in the bovine retina; 2) provide a "benchmark" of 3.01 ng/retina for normal adult retinae collected during photophase; and 3) indicate that HPLC-EC represents an adequately sensitive instrument for the detection and quantification of melatonin in a single bovine retina.

Animals

Treatment of hypertension in pregnancy by relaxation and biofeedback.

In a study of the effectiveness of systematic relaxation training alone or combined with biofeedback in the treatment of hypertension in pregnancy, 60 women were seen weekly for 6 weeks. 18 were given relaxation therapy alone (group A), 18 relaxation plus biofeedback (group B), and there were 24 controls. Whereas two-thirds of the control group had to be admitted to hospital during their pregnancies, less than a third of each experimental group had to be admitted. The experimental groups also had significantly lower systolic and diastolic blood pressure than the control group. There were no significant differences between groups A and B in hospital admission rates or blood-pressure measurements.

Adolescent