Zinc supplementation and erythropoiesis in the elderly.
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Aged↗
Biomedical subjects
M A Baker
Publications and source records attributed to M A Baker.
Aspirin enhances evaporation in hydrated and dehydrated rats.
The effect of acetysalicylic acid (aspirin) on thermoregulation in a warm environment was studied in hydrated and dehydrated adult rats to test the hypothesis that dehydration hyperthermia can be modified by an antipyretic drug. Metabolic rate (MR), evaporative water loss (EWL), and deep body temperature (Tb) were measured during 2 h of exposure to an ambient temperature of 36 degrees C after the rats had received an oral pellet of aspirin (100 mg.kg-1) or placebo. The dehydrated placebo group had a higher Tb and lower EWL than the hydrated placebo group. Aspirin increased MR and EWL in both hydrated and dehydrated animals. Aspirin did not affect Tb in hydrated rats, but reduced Tb by 0.2 degree C in dehydrated rats during the heat exposure. The elevation in EWL appears to be a thermoregulatory response to increased heat production in both hydrated and dehydrated animals after aspirin treatment. The possibility that aspirin may act in dehydrated animals to restore central thermosensitivity toward hydrated levels needs to be tested further.
Animals↗
Chemotherapy following surgery for stages IE and IIE non-Hodgkin's lymphoma of the gastrointestinal tract.
Twenty-six patients were treated with chemotherapy following surgery for gastrointestinal non-Hodgkin's lymphoma (GI-NHL). The median age was 50 years (range, 20 to 76). The primary site included stomach (16 patients), small bowel (seven), large bowel (two), and mesenteric nodes (one). Following surgery, nine patients had macroscopic and four patients had microscopic residual disease, and 13 were felt to have had complete surgical resection. Thirteen patients were stage I and 13 were stage II. Sixteen patients were treated with COPP (cyclophosphamide, vincristine, procarbazine, prednisone), nine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and one with CVP (cyclophosphamide, vincristine, prednisone). At a median follow-up of 50 months (8+ to 178+ months) ten of 12 stage I patients and nine of 14 stage II patients remain alive. Of the nine patients with macroscopic residual disease, four died of disease 6.5 to 11.0 months after diagnosis, and five are alive 8+ to 178+ months from diagnosis. Fourteen of the remaining 17 patients who had complete surgical resection are alive without disease. Death in the other three patients was due to multiple abdominal abscesses at 12 months, adenocarcinoma of the colon at 57 months, and dementia and progressive neurologic dysfunction at 65 months. No patient who had complete resection has relapsed or developed systemic disease after chemotherapy. These results suggest that complete surgical resection is an important prognostic factor and that chemotherapy without irradiation in completely resected localized GI-NHL can prevent local and systemic relapse resulting in long-term disease-free survival.
Adult↗
Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34.
Monoclonal antibodies of the CD34 class all recognize a monomeric cell surface antigen of approximately Mr 110,000 which is selectively expressed on human hemopoietic progenitor cells. This structure can be readily surface-labeled with [125I]actoperoxidase and by periodate-[3H]borohydride, but it labels only weakly with [35S]methionine, [35Sl]cysteine, 3H-amino acids, or 3H-mannose, even after prolonged labeling periods. However, the antigen is more efficiently labeled by [3H]glucosamine. Lectin binding studies, sensitivity to certain glycosidases, and gel filtration analysis of glycans released by alkaline hydrolysis indicate that this glycoprotein contains several complex-type N-linked glycans as well as several highly sialylated O-linked glycans. Western blotting experiments show that various CD34 antibodies fail to efficiently detect desialylated and/or de-N-glycosylated forms of the antigen. Experiments involving the use of tunicamycin, together with metabolic labeling studies, strongly suggest that this structure "turns over" very slowly in vivo. The CD34 antigen is not detectably labeled by 32P-phosphate in vivo, nor are immune complexes containing it associated with phosphokinase activity in vitro. Sequential immunoprecipitation and Western blotting studies indicate that this antigen is not a member of the leukosialin/sialophorin family despite the fact that these molecules share several structural similarities. Partial amino acid analysis of highly purified CD34 antigen revealed no significant sequence similarity with any previously described structures.
Amino Acid Sequence↗
Radiosensitization, thiol oxidation, and inhibition of DNA repair by SR 4077.
The mechanism of radiosensitization by diazenedicarboxylic acid bis(N),N-piperidide (SR 4077), a less toxic analog of diamide, was studied using Chinese hamster ovary cells. SR 4077 gave an average SER of 1.58 for postirradiation incubations of 0.5, 1.0, or 2.0 h. Intracellular GSH and protein thiols decreased rapidly following drug addition and GSSG increased. The GSH/GSSG ratio shifted to 1/1.6 after SR 4077 addition but returned to greater than 10/1 between 0.5 and 1.0 h. After 4 h, total intracellular GSH was only 58% of pretreatment level and extracellular GSSG increased. Protein thiols decreased to 18% of pretreatment values, recovered most rapidly between 0.5 and 1.0 h, and reached 87% of pretreatment level after 4 h. A decrease in DNA single-strand break repair as measured by alkaline filter elution rate over 0.5 h was seen, and the initial rate of repair was slower than in cells not treated with SR 4077. DNA double-strand break repair as measured by neutral filter elution rate was delayed during the first hour after irradiation when cells were treated with SR 4077. The times for maximum radiosensitization, GSH and protein thiol oxidation and recovery, and DNA strand break repair kinetics were closely linked. We propose that a protein thiol(s) required in repair processes was reversibly oxidized during SR 4077 treatment.
Animals↗
Acute leukemia occurring 19 years after treatment of acute lymphoblastic leukemia.
A 22-year-old woman presented with acute lymphoblastic leukemia (ALL) during pregnancy. She had been successfully treated for ALL at the age of 3 years and had received maintenance treatment for 11 years. Complete remission of 3 years or more is an important factor for long-term survival and potential cure. Relapses may occur in the first 5 years after maintenance is discontinued. Later relapses are distinctly unusual. We have found six more cases of ALL occurring long after the initial remission in the English literature. It is unclear whether late relapse represents true relapse or a second leukemia. Life-long follow-up of children with ALL may be necessary.
Acute Disease↗
Presence of cytidine 5'-monophospho-N-acetylneuraminic acid:Gal beta 1-3GalNAc-R alpha(2-3)-sialyltransferase in normal human leukocytes and increased activity of this enzyme in granulocytes from chronic myelogenous leukemia patients.
We have examined granulocytes from patients with chronic myelogenous leukemia (CML) and from normal subjects to determine whether activity of a specific sialyltransferase might account for the aberrant sialylation of O-linked membrane oligosaccharides in CML cells. Total membrane preparations of morphologically mature CML and normal granulocytes were tested for sialyltransferase activity using the substrates galactosyl-beta 1-3-N-acetyl-D-galactosamine-alpha-O-nitrophenyl and N-acetyl-D-galactosamine-alpha-phenyl. N-Acetyl-D-galactosamine-alpha-phenyl was not an acceptor with either CML or normal cells. With galactosyl-beta 1-3-N-acetyl-D-galactosamine-alpha-O-nitrophenyl, sialyltransferase activity was 2.8 times higher in CML cells compared to normal cells. Product identification by high performance liquid chromatography showed that enzyme from both normal and CML granulocytes linked sialic acid to galactosyl-beta 1-3-N-acetyl-D-galactosamine-R by the alpha(2-3) and not the alpha(2-6) linkage. The enzyme CMP-N-acetylneuraminic acid: galactosyl-beta 1-3-N-acetyl-D-galactosamine-R alpha(2-3)-sialyltransferase has not previously been described in human granulocytes. The marked increase in activity of this enzyme in CML and the resulting increase in sialylation may contribute to the pathophysiological behavior of CML granulocytes.
Antifreeze Proteins↗
Effect of verapamil and other agents on the distribution of anthracyclines and on reversal of drug resistance.
We studied the intracellular distribution of drugs within anthracycline-sensitive and -resistant cells by computer-assisted digitized video fluorescence microscopy. We found that the antitumor antibiotic, daunorubicin, distributes differently in anthracycline-sensitive and -resistant human leukemia cells (HL-60). Verapamil and other agents known to circumvent resistance in pleiotropic drug-resistant cell lines were able to change the pattern of distribution of daunorubicin in the anthracycline-resistant HL-60 cells back to the distribution found in anthracycline-sensitive HL-60 cells. To investigate the biochemical basis for this effect, we studied the distribution of daunorubicin and doxorubicin in a hydrophobic/hydrophilic (membrane/cytoplasmic) environment using the two-compartment cell-free system of Folch. Our results demonstrate that various unrelated drugs known to overcome resistance will also change the distribution of the anthracyclines in the hydrophobic/hydrophilic compartments. Our data allow the hypothesis that various unrelated agents known to circumvent resistance may act by altering the hydrophobic/hydrophilic solubility of anthracyclines in the resistant cell.
Antibiotics, Antineoplastic↗
Respiration in heat stressed camels.
Respiration and heat exchange in relation to brain temperature (Th) and body temperature (Tb) were investigated in four heat stressed camels subjected daily to high temperature (47 degrees C) in a climate chamber while resting when hydrated and dehydrated by approximately 10%, 15% and 20% of initial weight. Diurnally Tb followed patterns described previously. Th was usually 0.2-0.5 degrees C greater than Tb: occasional reversals with brain cooling were observed. Minute ventilation increased with Tb: above 37.5 degrees C it was approximately half as much in dehydrated as in hydrated animals. Respiratory frequency increased with Tb up to 60/min. Tidal volume fell with increasing frequency; above 25 breaths/min, tidal volume approximated dead space volume. Exhaled air was almost always unsaturated with no systematic effect of dehydration. Metabolic rate fell on dehydration reducing ventilatory demand. Th and Tb were measured in two of the animals walking outdoors: then Th fell below Tb if exercise exceeded 30 min. The data indicate that heat stressed camels pant, but turbinate vasoconstriction in a hot environment prevents cooling of the brain by carotid rete heat exchange.
Animals↗
The management of leukaemia in the elderly.
Leukaemia is relatively common in the elderly compared to the general population, with over half of all cases of leukaemia occurring in patients aged 65 and over. Special problems are associated with treating patients in this age group. The leukaemias may be intrinsically different, in part because of the high incidence of preceding myelodysplasia. There is increased likelihood of coincident disease. There is lower tolerance to toxic complications, such as infection and bleeding, associated with a decreased resilience of normal haematopoiesis. There is more difficulty in obtaining intravenous access in elderly patients. These problems render patients ineligible for marrow transplants. Myelodysplastic syndromes occur predominantly in the elderly. There are a number of myelodysplastic syndromes now identified, each with its characteristic natural history. Management decisions are based on accurate diagnosis of the specific syndrome, consideration of prognostic features, a period of observation, and conservative treatment principles. More than half the cases of acute myeloblastic leukaemia also occur in the elderly. Prognostic factors must be examined and the literature carefully scrutinized for results pertinent to the elderly patient. In some patients treatment may be justifiably withheld, others may benefit from low dose cytosine arabinoside and some patients should receive aggressive combination chemotherapy. Management of the chronic leukaemias in the elderly is a less controversial area. Chronic lymphocytic leukaemia is the most common of the leukaemias in this age group. Prognostic factors can be determined using staging criteria. observation alone is indicated in many patients. Chlorambucil and prednisone are the most widely used drugs for symptomatic disease. Aggressive combination chemotherapy may benefit a few patients with advanced or refractory CLL. Hairy cell leukaemia is a rare disorder but many of the patients are over age 65. The elderly male patient may have a particularly benign course and require no therapy. Splenectomy is the standard first line of therapy, but recombinant alpha-interferon is sufficiently effective and non-toxic that it should be the treatment of choice in some patients. Deoxycoformycin is also effective in preliminary trials and may soon be routinely indicated. It is not often appreciated that half of all patients with chronic myelogenous leukaemia are aged 65 and over.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Toward meaningful noise research.
The present review considers a series of studies of noise conducted in collaboration with Dr. Michel Loeb. This review attempts to provide a theoretical perspective as well as to summarize the most important findings of those studies. The work reviewed shows that noise effects interact with other variables, such that a noise effect on one sex is reversed for the other, and is also reversed at different times of the day. A second experiment confirmed this finding with a different arithmetic task. Further work indicated parallels between noise and fatigue, with aftereffects depending upon both work and noise. The final experiment repeated some of these findings with a different task battery of information processing tasks while showing that noise effects further depend on the meaningfulness of the noise background.
Circadian Rhythm↗
Acute leukemia during pregnancy: the Toronto Leukemia Study Group experience with long-term follow-up of children exposed in utero to chemotherapeutic agents.
The incidence of acute leukemia in pregnancy is low and even referral centers have limited experience. Although the short-term risks for children exposed in utero to cytotoxic agents are predictable, there is no information on long-term complications. We report here our experience in the treatment of seven cases of acute leukemia diagnosed during pregnancy, and a literature review of 51 cases published since 1975. Fifty-three patients received chemotherapy during their pregnancies. Forty-nine of the 58 cases resulted in the birth of 50 live infants. Twenty-eight infants were born prematurely, and four had low birth-weights for their gestational age. Thirty-three percent of the newborns exposed to chemotherapy in the last month of pregnancy were cytopenic at birth, but other perinatal complications were not increased. Only one child (present series) had obvious congenital malformations, and this same infant later developed a neuroblastoma arising in the adrenal gland and a papillary carcinoma of the thyroid. Follow-up data are not provided in most previously reported cases, but long-term follow-up of our cases from 1 to 17 years has shown normal growth and development and no further malignancies. A central registry is strongly advised in order to document the long-term complications arising in children exposed to chemotherapy in utero.
Abnormalities, Drug-Induced↗
Intrapulpal foreign objects: a case report.
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Child↗
Determining prognosis for cancer patients.
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Adult↗
Effects of ligands on gold inhibition of selenium glutathione peroxidase.
Gold inhibits selenium-dependent glutathione peroxidase (GSH Px) in vitro. Chrysotherapy has been used for over five decades without complete understanding of its pharmacodynamics. This study shows that gold is potentially an inhibitor of GSH Px in vivo. Reported are conditions for assay of GSH-Px activity showing that the inhibition by gold species can be reversed. The study demonstrates the high affinity of gold for the selenohydryl-active site of GSH Px relative to the affinities of other physiological ligands; GSH Px was inhibited to a greater extent by a small molecular-weight fraction isolated from kidneys of gold-treated rats than by the fraction isolated from kidneys of rats not treated with gold. The data provide a new perspective on the action of gold-containing drugs in vivo.
Animals↗
Structural and functional features of a cell surface phosphoglycoprotein associated with tumorigenic phenotype in human fibroblast x HeLa cell hybrids.
Monoclonal antibodies have been raised against a dimeric cell surface antigen (p75/150) which is specifically associated with the tumorigenic phenotype in human fibroblast X HeLa hybrids. During biosynthesis, a precursor molecule (p70/140), was associated with microsomal membranes in vivo but possessed no detectable cytoplasmic domains. At this stage, each p70 monomer contained 3 "high-mannose" type N-linked glycans which were subsequently processed into endoglycosidase H-insensitive complex oligosaccharides on the mature cell surface forms. Cleavage of this cell surface form with endoglycosidase F yielded non-N-glycosylated polypeptides of Mr = 60,000/120,000. All the monoclonal antibodies identified similar non-N-glycosylated polypeptides in cells grown in the presence of tunicamycin. p75/150 could be weakly labeled with [3H]palmitic or myristic acid. In vivo, p75/150 was found to be phosphorylated on serine residues. Immunoprecipitates of p75/150 from HeLa or tumorigenic hybrid cell lysates exhibited protein kinase activity in vitro, which phosphorylated p75/150 itself, also on serine residues. We were unable to detect this kinase activity in normal fibroblasts and in the nontumorigenic hybrid cells. Furthermore, we were unable to detect p75/150 or its precursors by either cell surface labeling, metabolic labeling, or Western blotting in nontumorigenic cell hybrids; p75/150 thus represents a tumor-specific marker in this system. Tryptic peptides of highly purified p75/150 have been generated, but their amino acid sequences did not reveal any significant homology with previously described proteins.
Amino Acid Sequence↗
Nonstress test and maternal position.
Antepartum evaluation of 225 low-risk primipara and 262 high-risk primipara and multipara using nonstress testing revealed 53 to be nonreactive when the test was performed in the supine position. When the test was repeated in the lateral decubitus position, it became reactive nonstress testing in 21 of these patients. This group of patients with a supine nonreactive nonstress test and a lateral reactive nonstress test demonstrated an associated compression of the abdominal aorta by the pregnant uterus in the supine, but not the lateral position. This study distinguishes three types of nonreactive nonstress tests: those due to placental insufficiency, those resulting from compression of the abdominal aorta by the pregnant uterus, and the falsely nonreactive. The percentage of false nonreactive nonstress tests results will be reduced by performing the test in the lateral decubitus position.
Aorta, Abdominal↗
Changes in the granulocyte membrane following chemotherapy for chronic myelogenous leukaemia.
Granulocytes from patients with chronic myelogenous leukaemia (CML) have been previously shown to have aberrant sialylation of membrane glycoproteins. We have examined the granulocytes from CML patients receiving intermittent chemotherapy to determine the relationship of the oligosaccharide changes to treatment. Compared to cells from non-leukaemic patients, granulocytes from untreated CML patients showed less adherence to nylon wool, decreased reactivity with peanut lectin, and decreased binding of the synthetic chemotactic peptide formyl-methionine-leucine-phenylalanine (FMLP). Granulocytes from CML patients treated with chemotherapy showed nylon wool adherence, peanut lectin reactivity and FMLP binding comparable to non-leukaemic cells. Chemotherapeutic agents may interfere with oligosaccharide synthesis with a resulting change in the composition of cell surface glycoconjugates.
Agglutination Tests↗