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Showing papers by "Howard Hughes Medical Institute published in 1978"


Journal ArticleDOI
TL;DR: In a family where the sickle gene was contained in a variant 13.0 kb fragment, restriction endonuclease mapping was used for antenatal diagnosis of sickle-cell disease and confirmed the diagnosis reached after investigation of a 100% sample of fetal blood.

328 citations


Journal ArticleDOI
TL;DR: The results indicate that the effect of E. coli L‐asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L‐glutaminase activity.
Abstract: The effects of E. coli L-asparaginase on cultured human pancreatic carcinoma (MIA PaCa-2) have been studied. The enzyme (1 U/ml) inhibited growth and protein synthesis in both MIA PaCa-2 and PANC-1, another pancreatic carcinoma cell line, but had little or no effect on human breast carcinoma or melanoma cells. The inhibition of protein synthesis by E. coli L-asparaginase was largely reversed by L-glutamine but not by L-asparagine. The growth of both MIA PaCa-2 and PANC-1 showed absolute dependence on L-glutamine. These results indicate that the effect of E. coli L-asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L-glutaminase activity. Although the addition of L-glutamine to the culture appeared to prevent cell death caused by L-asparaginase, it did not restore the ability of the cells to proliferate. Asparaginase derived from vibrio succinogenes, which is virtually free of L-glutaminase activity, was equally inhibitory to MIA PaCa-2 cell growth but did not affect protein synthesis. It is concluded that the inhibition of growth of cultured pancreatic carcinoma cells by E. coli asparaginase is a combined function of both its L-asparaginase and L-glutaminase activity.

73 citations



Journal ArticleDOI
TL;DR: Stabilizing agents should be added to diluting fluids in preparing allergens for skin testing or immunotherapy to prevent losses of allergenic activity during the process of making the extreme dilutions required with potent extracts.
Abstract: Intradermal skin testing may often give inaccurate results because of poor stability of allergens and loss of protein by adsorption to the walls of containers and syringes during the process of making the extreme dilutions required with potent extracts. To test the ability of stabilizers to prevent such losses of allergenic activity, three diluents for allergens were compared: standard phosphate-buffered saline (PBS), pH 7.4, containing 0.4% phenol and the same buffer containing either 0.03% human serum albumin (HSA) or 0.005% Tween 80. Tenfold dilution series of ragweed, grass, Altemaria , and dust allergens were tested by the intradermal threshold dilution technique in the same group of patients five times over six months, comparing stored dilutions with dilutions freshly made from the same batches of lyophilized extracts. Results with Tween 80 and HSA buffers were identical and highly reproducible; however, each new set of dilutions in standard buffers frequently showed within 24 to 48 hr after preparation a lower skin test potency which varied unpredictably between ten and one thousandfold. Furthermore, upon prolonged storage at 4 °C, dilutions in standard buffer lost further activity. Storage of radiolabeled antigen E (AgE) in ordinary glass tubes for 24 hr showed adsorption of about 5% of the labeled protein to glass in the absence of stabilizers but only 0.5% in the presence of stabilizers. We conclude that stabilizing agents should be added to diluting fluids in preparing allergens for skin testing or immunotherapy.

40 citations



Journal ArticleDOI
TL;DR: The results indicate that human bone marrow CFU-C's are heterogeneous and that the two purified CSF fractions from human lung have different CF U-C specificity.

26 citations


Journal Article
TL;DR: Simulation by PGF reflected an absolute increase in granulocytic colonies, whereas inhibition by PGE affected both granulocyte and macrophage colony formation, suggesting the relative levels of PGE and PGF may play a determining role in the modulation of granulopoiesis.

22 citations


Journal ArticleDOI
TL;DR: The nucleotide sequence of the entire 5' untranslated region of human gamma-globin mRNA has been determined by analyzing complementary DNA synthesized from the mRNA with reverse transcriptase and the hexanucleotide sequence CUUCUG is found near the 5' ends of all three human globin mRNAs, suggesting a possible role of this sequence or ribosomal binding.
Abstract: The nucleotide sequence of the entire 5' untranslated region of human gamma-globin mRNA has been determined. This was accomplished by analyzing complementary DNA (cRNA) synthesized from the mRNA with reverse transcriptase. The CDNA was labeled at its 3' end with 32"p using terminal deoxynucleotidyl transferase, digested with the restriction endonuclease Hae III and the end-labeled fragment isolated ans sequenced by the method of Maxam and Gilbert. Including the initiation codon AUG, the 5' untranslated region of human gamma-globin mRNA contains 57 nucleotides, compared to 41 in alpha- and 54 in beta-globin mRNA. There is very little homology between alpha and gamma sequences in the 5' region. There is considerable homology between beta- and gamma-globin mRNAs in the regions proximal and distal to the initiation codon, but the entire sequence shows less homology than the human and rabbit beta-globin mRNAs. The hexanucleotide sequence CUUCUG is found near the 5' ends of all three human globin mRNAs, suggesting a possible role of this sequence or ribosomal binding. Both guanosine and cytidine were found at the 19th nucleotide position from the 5' end of the gamma mRNA. We believe this heterogeneity arises from the difference in nucleotide sequence between the A gamma and G gamma loci.

19 citations


Journal ArticleDOI
TL;DR: The effects of anemia and hypoxia on erythropoiesis in Lepisosteus platyrhincus were examined in this paper, where cells morphologically similar to erythroblasts appeared in the circulation and their appearance was paralleled by increases in δ-aminolevulinic acid and 3 H-thymidine uptake by peripheral blood cells.

19 citations


Journal ArticleDOI
TL;DR: It was concluded that the initial presence of HBeAg correlated with the persistence of HBsAg because 15 of the 16 H beAg + patients were stillHBsAg + at death or last follow-up, whereas 7 of the 8 HBe Ag − patients had become HBs Ag − at a mean period of 3.8 months.

19 citations


Journal ArticleDOI
TL;DR: A nasopharyngeal carcinoma occurred in a 41-year-old white woman who had received Fowler's solution (potassium arsenite) almost yearly for more than 20 years for the treatment of psoriasis.
Abstract: • A nasopharyngeal carcinoma occurred in a 41-year-old white woman who had received Fowler's solution (potassium arsenite) almost yearly for more than 20 years for the treatment of psoriasis. Palmar and plantar keratoses were present. Because of the rarity of this malignant neoplasm in white people, a relationship with arsenic ingestion is suggested. ( Arch Dermatol 114:602-603, 1978)

Journal ArticleDOI
TL;DR: Serum-free conditioned medium prepared from these cultures provides an excellent source of CSF and propagating cell lines from autopsy lung tissue which secrete CSF into the medium overcome considerable difficulty in purification.

Journal ArticleDOI
TL;DR: The importance of α-amyl enzyme in achieving efficient conversion of starch into glucose is illustrated by a comparison of the time courses of degradation of amylopectin by glucoamylase preparations containing low and high levels ofα- amylase.

Journal ArticleDOI
TL;DR: Hemoglobins D-Los Angeles and Aida were encountered in an Asian Indian, unassociated with any clinical manifestations, and the identical change in isoelectric points of the two variants produced an interesting electrophoretic pattern.
Abstract: Hemoglobins D-Los Angeles (β 121 Gin) and Aida (α64 Asn) were encountered in an Asian Indian, unassociated with any clinical manifestations. These hemoglobins had normal oxygen affinities and were stable to heat and isopropanol. The ratio of α chain synthesis to β chain synthesis was close to unity. The identical change in isoelectric points of the two variants produced an interesting electrophoretic pattern.The coexistance of more than one hemoglobin variant in an individual or family has provided valuable

Journal ArticleDOI
TL;DR: It is concluded that guanadrel sulfate may be useful in the symptomatic management of patients with thyrotoxicosis and proximal and distal muscle strengths were initially decreased, when compared with healthy subjects, and improved substantially with guanADrel therapy.
Abstract: Eleven patients with Graves' disease were treated with guanadrel sulfate and observed for changes in neuromuscular and cardiovascular manifestations. No notable changes in pulse rate or muscle strength were detected in either these patients during a three-day pretreatment period or in five control patients with Graves' disease receiving placebo for six days. Thyroid hormone levels were not altered by seven days of guanadrel sulfate therapy (5 to 20 mg orally every six hours), and no adverse side effects were encountered. Mean supine resting pulse fell from 102 ± 6 (mean ± SEM) to 90 ± 3 beats per minute ( P ( Arch Intern Med 138:1106-1108, 1978)