Hb Le Lamentin or alpha 2 20(B1)His----GLN beta 2 found in a Spanish family.
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Biomedical subjects
Publications and source records attributed to H Hu.
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We have analyzed the sequence of the beta globin gene of a chromosome that is linked to the occurrence of an inclusion body beta-thalassemia characterized in the heterozygote by moderate anemia, severe red cell abnormalities, splenomegaly, inclusion body formation, elevated Hb A2 levels, and an increased in vitro alpha/beta chain synthetic ratio. The data indicate a change in codon 114 from CTG (Leu) to -GG that resulted in a frameshift and the presumed synthesis of an abnormal beta chain that is 156 residues long with a completely different C-terminal amino acid sequence. The change in codon 114 gives a -GGGCCC- sequence that creates a new ApaI site; the resulting 2.6-kilobase fragment has been observed in all subjects with this thalassemia condition. Protein structural analyses failed to demonstrate any trace of the abnormal beta chain, even in reticulocytes and nucleated red cells that were isolated by density gradient centrifugation. The inclusion bodies appear to contain mainly normal alpha chains. It is assumed that the structure of the beta-Geneva chain prevents it from combining with normal alpha chains; this results in a rapid breakdown of the abnormal protein during the early stages of red cell maturation and an accumulation of free alpha chains.
This report describes a new fetal hemoglobin variant, Hb F-Xinjiang, which was observed in a newborn baby of the Han nationality. Its electrophoretic mobility at pH 8.6 was slower than that of Hb D. Structural analyses identified the variant as A gamma T25(B7)Gly----Arg. Heat stability test showed that the variant was unstable.
A slow-moving gamma chain variant was discovered in the cord blood of an infant born to parents of the Han nationality from Jiangsu. The variant, which migrated electrophoretically at alkaline pH between Hb A and Hb D, was characterized by an Asp----His substitution at gamma 73, while residues gamma 75 and gamma 136 were occupied by Ile and Ala, respectively. As the A gamma T-chain was also present, this baby has two types of abnormal gamma-chain. The variant was named Hb F-Xin-Su.
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The distribution pattern of adrenocorticotropin-like immunoreactivity (ACTH-LI) in cats using the avidin-biotin modification of an immunocytochemical method shows cell bodies containing ACTH-LI in the medial basal hypothalamus, especially in the infundibular nucleus. The fibers from these neurons extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus coeruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. The distribution pattern of the cell bodies and fibers containing ACTH-LI bears several similarities to that seen in rats. The pattern differs from that of rats in the fact that the termination in the amygdala is more extensive and that ACTH-LI was not observed in cell bodies in any location other than the medial basal hypothalamus.
The suprageniculate nucleus of the posterior thalamus is a source of non-intralaminar thalamic nucleus which projects selectively to the medial and intermediate regions of the caudate nucleus in cats.
The carcinogenic effects of di(2-ethylhexyl) phthalate (DEHP), including its potential as an initiator and as a promoter of carcinogenesis, were studied in mouse liver and skin and in rat liver in vivo, and in mouse epidermis-derived JB6 cells in vitro. A mouse model for liver initiation and promotion involved initiation by injection of N-nitrosodiethylamine (DEN) intraperitoneally into male B6C3F1 mice at 4 weeks of age, followed by exposure to either DEHP in the diet (3000, 6000, or 12,000 ppm) or phenobarbital in the drinking water (500 ppm), beginning 1 to 2 weeks later and continuing for periods of from 1 day to 18 months. Female F344/NCr rats were subjected to a similar protocol in which promotion continued for 14 weeks. DEHP promoted focal hepatocellular proliferative lesions (FHPL), including hyperplastic foci and neoplasms initiated by DEN in mice but not in rats. Skin-painting studies in female CD-1 or SENCAR mice involved initiation by a single topical exposure to 7,12-dimethylbenz[a]-anthracene (DMBA) applied to the dorsal skin, followed by repeated percutaneous exposure to a tumor promoter, either DEHP or 12-O-tetradecanoylphorbol-13-acetate (TPA). To test for two-stage skin tumor promotion, SENCAR mice were initiated with DMBA and then TPA was administered for only 2 weeks, after which DEHP was subsequently administered for 26 weeks. DEHP displayed very weak complete promoting activity and definite second stage promoting activity in SENCAR mouse skin, but was inactive under our conditions on CD-1 mouse skin. In vitro promoting activity of DEHP and its hydrolysis products, mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol (EH), was studied by using promotable mouse epidermis-derived JB6 cells. DEHP and MEHP promoted JB6 cells to anchorage independence, while EH did not.
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Data from the medical treatment group of the Aspirin in TIA study were reviewed, and prospective analysis of patients with asymptomatic bruits was performed to see whether carotid stenosis (0 to 49% or 50 to 99%) or ulceration produced an increased risk of ipsilateral TIA or infarct. In symptomatic arteries, greater than 50% stenosis without ulceration implied a higher risk of subsequent symptoms. Ulceration was associated with an increased risk only in nonstenotic vessels. Lesion anatomy was not related to outcome in asymptomatic arteries, and the incidence of cerebral infarct was low. Factors other than anatomy must play a large role in determining subsequent risk.
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BACKGROUND: The inherent limitations of [E1-]Ad vectors as gene therapy vehicles suggest that further modifications may improve their overall performance profiles. However, Ad vector modifications can have untoward effects on their basic biology, e.g., some helper-virus dependent Ad vectors have been found to be unstable without the presence of preterminal protein (pTP) activities. Despite this concern, we generated a new class of helper-virus independent Ad vector that was multiply deleted for the E1, polymerase, and pTP genes, and investigated the ramifications of these deletions upon several vector performance parameters. METHODS: The construction and propagation of an [E1-, polymerase-, pTP-]Ad vector was achieved with the use of trans-complementing cells co-expressing the Ad E1, polymerase and pTP genes. RESULTS: High titer production of the [E1-, polymerase-, pTP-]Ad vector was successfully accomplished via conventional Ad purification techniques. This unique class of Ad vector was capable of long-term gene transfer in vivo (despite lacking pTP functions) that was concomitant with a significantly decreased hepatic toxicity. CONCLUSIONS: Previous studies had suggested that Ad genome persistence in vivo may be dependent upon the presence of low level vector genome replication and/or pTP functions. Our results suggest that [E1-, polymerase-, pTP-]Ad vectors can overcome these barriers. The further benefits afforded by the use of this class of Ad vector (increased cloning capacity, high level growth, decreased propensity to generate replication competent Ad (RCA), decreased toxicity) suggests that they will be highly beneficial for use in several aspects of human gene therapy.
The innervation of Meissner's corpuscles (Mc) is complex, consisting of different types of sensory nerve fibers. We investigated the neurochemistry of Mc in human digital skin by indirect immunofluorescence, using a wide panel of both general neuronal as well as neurotransmitter-related molecules. Structural proteins (protein gene product 9.5, neuron-specific enolase, neurofilament) were found to consistently label the entire neuronal component of Mc. Immunoreactivity for gamma-melanocyte stimulating hormone was detected in the large diameter fibers running spirally within the corpuscles, while a number of peptide transmitters (substance P, calcitonin gene-related peptide, neurokinin A, galanin, somatostatin) were found in the thin unmyelinated fibers in both intra- and extracorpuscular locations.