Copper supplementation in premature infants.
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Copper↗
Biomedical subjects
L Hall
Publications and source records attributed to L Hall.
The use of the red cell surface antigen to predict the malignant potential of transitional cell carcinoma of the ureter and renal pelvis.
This is the first report on the use of the red cell surface antigen test in predicting the malignant potential of transitional cell carcinoma of the ureter and renal pelvis. In 29 cases evaluated there was an 80 per cent correlation. The red cell surface antigen determination was shown to have practical value in the management of these tumors.
Antigens, Surface↗
5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons.
In an attempt to stimulate Hb F synthesis in baboons by means other than erythropoietic stress, we considered the possibility that an agent that inhibits methylation of CpG sequences in DNA may be effective. 5-Azacytidine, a cytosine analogue that cannot be methylated, is such an agent. Animals whose packed red cell volume was maintained at approximately 20% by bleeding were given 10 daily intravenous injections of the drug (6 mg/kg) in 12 days. Hb F levels in these animals started to increase on day 5 of this regimen and peak levels, which were 6-30 times higher than those produced by bleeding alone, occurred 5-7 days after the last dose of the drug. In animals previously identified as genetically "high" or "low" Hb F responders, the maximal Hb F levels were 70-85% and 35-40% respectively. In dose-response studies 5-azacytidine given daily at 3-4 mg/kg produced maximal Hb F increases. The drug did not correlate the percentage (number) of Hb F-containing cells (F cells) beyond the maximal number achieved by bleeding alone and thus its main effect was to increase Hb F per F cell. The finding that Hb F synthesis can be modulated to such a high degree by a drug may have therapeutic implications--e.g., in sickle cell anemia, in which stimulation of Hb F synthesis may prevent sickling.
Animals↗
The construction and partial characterization of plasmids containing complementary DNA sequences to human calcitonin precursor polyprotein.
(1) Total poly(A)-containing RNA isolated from human thyroid medullary carcinoma tissue was shown to direct the synthesis in the wheat germ cell-free system of a major (Mr 21000) and several minor forms of human calcitonin precursor polyproteins. Evidence for processing of these precursor(s) by the wheat germ cell-free system is also presented. (2) A small complementary DNA (cDNA) plasmid library has been constructed in the PstI site of the plasmid pAT153, using total human thyroid medullary carcinoma poly(A)-containing RNA as the starting material. (3) Plasmids containing abundant cDNA sequences were selected by hybridization in situ, and two of these (ph T-B3 and phT-B6) were characterized by hybridization--translation and restriction analysis. Each was shown to contain human calcitonin precursor polyprotein cDNA sequences. (4) RNA blotting techniques demonstrate that the human calcitonin precursor polyprotein is encoded within a mRNA containing 1000 bases. (5) The results demonstrate that human calcitonin is synthesized as a precursor polyprotein.
Calcitonin↗
Heterogeneity of guinea-pig caseins synthesized and sequestered by cell-free protein-synthesizing systems.
1. Individual mRNA species encoding guinea-pigs caseins A, B and C, and alpha-lactalbumin, were purified by hydridization to recombinant milk-protein plasmid DNA immobilized on diazobenzyloxymethyl-paper or diazobenzyloxymethyl-cellulose. Addition of the purified mRNA species to a reticulocyte-lysate cell-free system, in the presence or absence of a dog pancreas microsomal membrane fraction, established a precursor-product relationship between the primary translation products and those sequestered within microsomal vesicles, as determined by polyacrylamide-gel analysis in one and two dimensions. 2. Three sequestered variants of sequestered casein A were identified, but only single forms of sequestered casein B and alpha-lactalbumin. Sequestered variants of casein C proved to be unexpectedly basic, and did not focus on the pH gradient utilized. 3. Comparative analysis of milk proteins synthesized in the reticulocyte-lysate and wheat-germ cell-free systems by two-dimensional gel electrophoresis demonstrated both quantitative and qualitative differences. In particular, marked but variable heterogeneity was apparent within the primary translation products of casein A and casein B. Pre-casein C did not focus. Limited N-terminal processing of the primary translation products was also evident. These observations are discussed in relation to (i) unscheduled post-translational modifications by cell-free protein-synthesizing systems and (ii) multiplicity of signal sequences. 4. Overall we demonstrate that complex precursor-product relationships between primary translation products and their sequestered variants, programmed in vitro by a mixed mRNA population, may be readily analysed by using individual mRNA sequences purified by hybridization to immobilized cloned complementary-DNA sequences.
Animals↗
alpha-Lactalbumin is not a marker of human hormone-dependent breast cancer.
It has been proposed that milk protein gene expression in human breast carcinomas may indicate a functional oestrogen receptor mechanism, and may therefore be diagnostic of tumours responsive to endocrine therapy. Unfortunately this has not been proved, largely because of inconsistencies in the immunoassay procedures used to identify milk proteins, in particular alpha-lactalbumin, in tissue extracts or serum. Alternative procedures include the identification of milk protein mRNA by cell-free protein synthesis, and the identification of milk protein RNA transcripts by hybridization to a sequence-specific probe. Here we describe experiments using alpha-lactalbumin cDNA probes, purified using recombinant plasmids, which demonstrate that although polyadenylated and non-polyadenylated alpha-lactalbumin transcripts are present in normal human mammary tissue during pregnancy and lactation, alpha-lactalbumin transcripts are not detectable in the human tumour tissues studied. These experiments do however show that a peptide, which shares antigenic determinants with human alpha-lactalbumin is present in some breast tumour tissues.
Breast Neoplasms↗
The construction, identification and partial characterization of plasmids containing guinea-pig milk protein complementary DNA sequences.
A complementary DNA (cDNA) plasmid library has been constructed in the plasmid pAT153, using poly(A)-containing RNA isolated from the lactating guinea-pig mammary gland as the starting material. Double stranded cDNA was inserted into the EcoRI site of the plasmid using poly(dA . dT) tails, then transformed into Escherichia coli HB101. From the resulting colonies we have selected and partially characterized plasmids containing cDNA copies of the mRNAs for casein A, casein B, casein C and alpha-lactalbumin. However, the proportion containing casein C cDNA was exceptionally low, and these contained at best 60% of the mRNA sequence.
Animals↗
The construction, identification and characterisation of plasmids containing human alpha-lactalbumin cDNA sequences.
We describe the cloning of double-stranded cDNA synthesized from lactating human mammary gland total poly(A)-containing RNA, into the EcoRI site of the plasmid pAT153. Nine recombinants were shown to contain alpha-lactalbumin cDNA sequences as determined by positive hybridisation translation of complementary RNA. Restriction enzyme maps were determined for six of these. Alignment of the restriction map with the known amino acid sequence of human alpha-lactalbumin provided evidence that two plasmids, designated phO-53 and phB-35, contained the complete coding sequence of the primary translation product (pre-alpha-lactalbumin). Hybridisation studies using purified human, monkey and guinea-pig alpha-lactalbumin cDNA demonstrated that greater nucleotide sequence divergence has occurred within the rodents than the primates, and that rodent alpha-lactalbumin mRNAs retain regions of homology with primate alpha-lactalbumin mRNAs.
Animals↗
Factors affecting the breathing rate of mice as used for studies of radiation damage to lungs.
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Aging↗
The effects of naloxone on methylphenidate-induced mood and behavioral changes: a negative study.
The effects of naloxone on IV methylphenidate-induced mood, behavior, and neurohumoral changes were assessed in eight psychiatric inpatients. While methylphenidate alone produced anticipated changes, the indications for significant naloxone-methylphenidate interactions were minimal. It is speculated that larger doses of naloxone might be required to produce modification of the psychostimulant effects.
Behavior↗
Effect of dextran-S (alpha, 1-3 dextran) on the growth of plasmacytomas MOPC-104E and J558.
The murine plasmacytomas MOPC-104E and J558 secrete IgM-lambda and IgA-lambda, respectively, which are antibodies to alpha, 1-3 dextran, a constituent of dextran-S (DEX-S) extracted from Leuconostoc mesenteroides. A single i.p. injection of 10 microgram DEX-S into BALB/c mice from 7 days before and up to 3 days after the implantation of 5 x 10(3) plasmacytoma cells protected the BALB/c mice from developing the tumors. Immunization with other antigens, such as Escherichia coli lipopolysaccharide, inulin (alpha, 1-6 linkage), and dextran T-10 (no known alpha, 1-3 linkages) did not protect the mice from developing the tumors. Growth of LPC-1 was not affected by DEX-S. The mechanism of this growth inhibition is unknown. It does not appear to depend solely on binding of antigen to tumor cells, and the limits of the effective time intervals between antigen and tumor injection suggest dependence on the presence of antibody to alpha-1,3 dextran.
Animals↗
mRNA species directing synthesis of milk proteins in normal and tumour tissue from human mammary gland.
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Adenocarcinoma↗
Spontaneous regression of Friend murine leukemia virus-induced erythroleukemia. IV. Effects of radiation and athymia on leukemia regression in mice.
The spontaneous regression of the erythroleukemia induced by the regressing Friend murine leukemia virus (F-MuLV) complex was inhibited by irradiation of the animals prior to F-MuLV inoculation. This inhibition was proportional to the dose of radiation used. Treatment of the mice with the bone-seeking isotope 89Sr also inhibited erythroleukemia regression, which implicates the same effector mechanisms involved in the resistance to F-MuLV or F-MuLV-induced immunosuprression. Erythroleukemias induced in athymic nude mice by the regressing F-MuLV complex exhibited higher rates of lethality than did the leukemias in heterozygous or homozygous thymus gland-containing controls. These data suggested the involvement of the immune system in erythroleukemia regression and the specific participation of thymus cells and an 89Sr-susceptible function, perhaps marrow-dependent cells, in the process of regression.
Animals↗
Metabolic stability of the extrachromosomal ribosomal RNA genes in the slime mould Physarum polycephalum.
The rRNA genes of the slime mould Physarum polycephalum are located on free, linear DNA molecules of a discrete size, Mr=38X10(6). Using an isotope dilution technique we have examined the metabolic stability of these extrachromosomal genes during active, balanced growth. Microplasmodia, prelabelled with [3H]thymidine, were used to prepare synchronous surface plasmodial cultures which were subsequently grown on unlabelled medium. The gross synthesis of ribosomal DNA was then determined over three consecutive mitotic divisions from the ratio of 3H to 14C in a hybrid formed between the extracted ribosomal [3H]DNA and a [14C]rRNA probe. It was found that ribosomal DNA, like chromosomal DNA, is completely stable during active growth.
Drug Stability↗
Synthesis and transport of myosin in Physarum polycephalum.
Immunological techniques have been used to study the rate of synthesis and intracellular transport of myosin in the slime mould Physarum polycephalum. Quantitative precipitation of myosin in homogenates of Physarum was achieved using an antimyosin antibody produced in rabbit in response to purified Physarum myosin. Dodecylsulphate-gel electrophoresis revealed that about 50% of the precipitated material is myosin. The rates of synthesis of total cellular protein and myosin were measured over the mitotic cycle. Both were found to increase exponentially or linearly between two successive nuclear divisions. Similarly, no difference in the proportion of myosin-synthesising polysomes, assayed by precipitation with antimyosin serum, could be detected between the S phase and G2 phase of the mitotic cycle. Myosin makes up nearly 2% of total plasmodial proteins. Its transport into the nucleus occurs predominantly during the G2 phase.
Animals↗
The organisation of genes for transfer RNA and ribosomal RNA in amoebae and plasmodia of Physarum polycephalum.
1. Using hybridisation techniques nuclei from both amoebae and plasmodia of Physarum polycephalum were found to contain 275 genes each coding for 5.8-S, 19-S and 26-S rRNA, 685 genes for 5-S rRNA and 1050 genes for tRNA. 2. Hybridisation of these RNA species to both amoebal and plasmodial DNA fractionated on CsCl gradients reveal that the 5.8-S, 19-S and 26-S rRNA genes are located at a satellite position (formula: see text) with respect to the main band of DNA, whereas 4-S RNA genes are located exclusively in the main band of DNA (formula: see text). 3. This result was confirmed by demonstrating that only the 5.8-S, 19-S and 26-S rRNA species hybridise to purified plasmodial ribosomal DNA. 4. The 19-S and 26-S rRNA genes of amoebae are located on extrachromosomal DNA molecules of a discrete size (Mr = 38 X 10(6)) with identical properties to plasmodial ribosomal DNA.
Cell Nucleus↗
Spontaneous regression of Friend virus-induced erythroleukemia. II. regression of Friend murine leukemia virus-induced lymphocytic leukemia.
We characterized several aspects of spontaneous regression of lymphocytic leukemia in mice. The disease, induced by the helper murine leukemia virus (MuLV) component obtained from the regressing Friend virus complex (RFV), was characterized by spleen and lymph node enlargement, thymus involvement, and anemia. Leukemia regression occurred in about 25% of infected mice and resulted in the return of lymphoid organs to near-normal weight and normal histology and the recovery from anemia. A tenfold to 1,000-fold decrease in virus titer was seen in those mice in which leukemia regressed when compared to leukemic animals, although infectious virus was still recoverable from apparently normal spleens. The sera of mice in which leukemia regressed contained potent virus-neutralizing activity that was associated mainly with immunoglobulins. These studies firmly supported the evidence that the regressing phenotype of RFV was due to its helper MuLV component (MuLV-RF).
Animals↗