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Biomedical subjects

A Liu

Publications and source records attributed to A Liu.

At least 217 records · Page 12Linked to original sources

Fluorine-18-labeled androgens: radiochemical synthesis and tissue distribution studies on six fluorine-substituted androgens, potential imaging agents for prostatic cancer.

We have synthesized six androgens labeled with 18F as potential imaging agents for prostatic cancer. These include 16 beta-fluorine-substituted testosterone, dihydrotestosterone and mibolerone, 16 alpha- and 16 beta-fluorine substituted 7 alpha-methyl-19-nortestosterone, and 20-fluoro-R1881 (metribolone). All of the radiochemical preparations proceeded in satisfactory yield, giving material with adequately high effective specific activity for the in vivo studies. In the tissue distribution studies in diethylstilbestrol-treated male rats, high selective uptake by the prostate was observed that ranged from 0.39% to 1.21% injected dose (ID)/g at 1 hr and 0.20 to 0.47 at 4 hr, with prostate-to-blood and prostate-to-muscle ratios ranging from 3.28 to 9.45, respectively, at 1 hr and 4.06 to 35.0, respectively, at 4 hr. Those compounds that are likely to be metabolized rapidly showed lower prostate uptake but higher uptake selectivity at 4 hr; at earlier times, uptake selectivities were more comparable. Compounds with a 16 beta-fluorine substituent showed extensive metabolic defluorination, resulting in ca. 50% of the dose being deposited in bone at 4 hr. This is consistent with a 16 alpha-hydroxylation process that may proceed rapidly with these compounds, but would be retarded by a 17 alpha-methylation, blocked by inversion of stereochemistry at C-16, and would not affect fluorine at the C-20 position. These fluoroandrogens, together with 20-fluoromibolerone described previously, are the first positron-emitting androgens to show high affinity and selective uptake by androgen target tissues in vivo, and they may be useful as in vivo prostate imaging agents in man.

Animals↗

Experience with the island inferior gluteal thigh flap compared with other local flaps for the reconstruction of the pelvic area.

The pelvic area can be one of the most difficult areas in the body to reconstruct. We divide pelvic wounds into three functional categories: spinal cord injury with no sensation or motor function, spinal cord injury with partial sensorimotor function, and miscellaneous injury, such as that resulting from congenital causes, trauma, or tumor resection. We have found the posterior thigh, particularly the island inferior gluteal thigh flap, to be an excellent choice for all three types of wounds, with the added advantages of sensate coverage and sparing of ambulation musculature in patients for whom such aspects are important. We have found that designing flaps based on the vascular territories of major blood vessels--the angiosome approach described by Taylor and Palmer--provides an excellent and reliable flap for most wounds in the pelvic area. In most patients, the major source vessel is the inferior gluteal artery and the flap is taken as an island flap. When this is not possible or when the island flap does not offer an advantage, we have chosen other local flaps. Our report covers our experience with 36 such procedures in 31 patients, with follow-up ranging from 3 months to 2 years.

Adolescent↗

Gene mapping in the idiopathic generalized epilepsies: juvenile myoclonic epilepsy, childhood absence epilepsy, epilepsy with grand mal seizures, and early childhood myoclonic epilepsy.

Idiopathic generalized epilepsies, i.e., juvenile myoclonic epilepsy (JME), childhood absence epilepsy, and epilepsy with grand mal [generalized tonic-clonic seizures (GTCS)], are the most common genetic epilepsies. Linkage studies using Bf, HLA serologic, and DNA markers by three independent investigators, one from Los Angeles and two from Berlin, have localized the JME locus to the short arm of chromosome 6 (6p). Because members of the same JME family have the same JME phenotype of childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or early childhood myoclonic epilepsy (ECME), our observations give evidence for a single-locus etiology in 6p for JME and for at least some of the childhood absence seizures, epilepsy with grand mal (GTCS) seizures, and ECME. Studies should now address whether locus heterogeneity exists within childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or ECME. Markers linked to JME (Bf, HLA serologic, and DNA markers in the DQ region) can be used to resolve etiologic heterogeneity. Using such markers, both linked and unlinked forms of phenotypes that are clinically indistinguishable may be detected and provide evidence for etiologic heterogeneity. Studies should also concentrate on narrowing the JME locus to 2 to 3 cm by screening families with recombinant events using RFLPs, candidate genes, and new expressed sequences on chromosome 6.

Adolescent↗

Fuzzy Logic for medical expert systems.

The use of linguistic approximation enables knowledge to be represented in a more meaningful way and this is especially important in medical domain as it involves a lot of subjective decision making; Fuzzy Logic, introduced by Zadeh, has the ability to represent this imprecise expression. In this paper, an alternative approach of Fuzzy Logic in handling the approximate reasoning in expert systems will be described. The approach does not use the General Modus Ponen on the compositional rule of inference, but instead it uses a collection of rules to specify the properties of the inference (in making decision). An example of medical domain is described as its application.

Diagnosis, Computer-Assisted↗

Mapping the gene for juvenile myoclonic epilepsy.

The practice of epileptology at a molecular level, where gene products are identified by gene mapping, will soon be possible for a growing number of epilepsies. Juvenile myoclonic epilepsy (JME) is the first of such epilepsies to be mapped to a chromosome, namely chromosome 6p21.3. Family studies of 68 JME probands from California revealed 50% of all families reported seizures in first- or second-degree relatives. Twelve percent of all family members other than the proband had epileptic seizures. Eighty percent of symptomatic siblings and 6% of asymptomatic siblings had diffuse 4- to 6-Hz multispike-wave complexes. Twelve percent of asymptomatic parents had diffuse, nonspecific slow waves mixed with spikes or sharp waves. JME is tightly linked to the Bf-HLA loci in chromosome 6. No matter what mode of inheritance is assumed, linkage to the clinical manifestations of JME and its associated EEG traits is indicated by lod scores over 3.0, as long as "EEG affected" but clinically asymptomatic family members are counted as affected during LIPED analysis. Studies are now being done to further localize the JME site. At the same time, further linkage studies should decide if JME is heterogeneous within itself and whether the same JME site in 6p21.3 underlies absence and grand mal epilepsies.

Child↗

Regulation of plasma lipid transfer by the high-density lipoproteins.

Mechanisms that regulate the activity of the plasma cholesteryl ester transfer protein (lipid protein transfer-I) are poorly understood. We have examined the role of endogenous regulators of the lipid transfer process, in particular the plasma high-density lipoproteins (HDLs), in both humans and two species previously reported to be devoid of cholesteryl ester transfer activity, the rat and the pig. Chromatography of d greater than 1.21 g/ml plasma on phenyl-Sepharose either enhanced (human) lipid transfer activity or unmasked (rat and pig) a nearly completely suppressed lipid transfer activity. The HDLs (either native or delipidated) were shown to be a rich source of a plasma lipid transfer inhibitor protein. Partial purification of the HDL-derived lipid transfer inhibitor protein was achieved by sequential chromatography on phenyl- and DEAE-Sepharose. Additional analysis of plasma from patients with very low (Tangier disease), normal, or very high levels of HDL cholesterol (hyperalphalipoproteinemia) revealed a significant inverse correlation between plasma cholesteryl ester transfer activity and the subjects HDL cholesterol level. These results suggest that circulating levels of the plasma high density lipoproteins may be an important determinant of plasma cholesteryl ester transfer activity, through the function of the HDL-derived lipid transfer inhibitor protein.

Animals↗

Distribution of vascular resistance in terminal arteriolar networks of cat sartorius muscle.

Morphometric information on the terminal arteriolar networks (n = 10) in cat sartorius muscle [Koller et al., Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H154-H164, 1987] is utilized in the calculations of distribution of vascular hindrance throughout the networks. These networks have tree-type geometry, i.e., they do not contain closed loops. The results are discussed in terms of simulated flow distribution. The flow calculations are based on the exact geometry of the arteriolar networks (the control and dilated diameter and the length of each vascular segment) and on assumed values of postarteriolar resistances. Three cases of postarteriolar resistances are considered: zero, constant, and randomly distributed. With zero postarteriolar resistances, the distribution of flow in the terminal arteriolar segments would be highly heterogenous. The simulated flow in each terminal segment is determined primarily by the number of bifurcations on the pathway leading to the terminal segment, with a slight compensation for the length of the pathways. The coefficient of variation of flow in the control state, CV(Qc), would be close to the value in the dilated state, CV(Qd). When each of the terminal segments is connected to a constant postarteriolar resistance, the CV's in both states decrease. The coefficient of variation in the dilated state becomes significantly smaller than in the control state. When postarteriolar resistances are randomly distributed, both CV's increase, and their values become closer to each other. These results suggest that postarteriolar resistances may play a very important role in distribution of flow in the microvascular network. This study formulates a framework for the quantification of the effect of arteriolar dilation on flow redistribution in the network.

Animals↗

Analysis of vascular pattern and dimensions in arteriolar networks of the retractor muscle in young hamsters.

A quantitative analysis of the distribution of microvascular blood flow and oxygen delivery requires a detailed description of the vascular network geometry. The distributions of lengths and diameters were determined in terminal arteriolar networks of the cheek pouch retractor muscle of young (34 +/- 2 days) hamsters. We compared the Strahler centripetal vessel ordering scheme, which assigns lowest order to the capillaries and proceeds upstream toward the larger vessels, with the centrifugal ordering scheme, which begins with the input arteriole and proceeds downstream toward the capillaries. The terminal networks of the retractor muscle typically contain 2 to 4 Strahler orders and 2 to 6 centrifugal orders. The coefficients of variation of diameter and length are smaller for Strahler ordering than for centrifugal ordering. In addition, for Strahler ordering, we found that the sequence of number of vessels obeyed Horton's law. We have compared three different methods of calculating the bifurcation, diameter, and length ratios. As an alternative method for analyzing network topology, we also studied the distribution of the number of segments on each pathway from the inlet of a network to a capillary. The information obtained from this analysis is useful for the mathematical modeling of flow in the microvascular network.

Animals↗

Quantitative analysis of arteriolar network architecture in cat sartorius muscle.

The geometry of the arteriolar network is one of the major determinants of blood flow distribution within a tissue. The purpose of this study was to describe the distribution of geometrical variables (lengths, diameters) as well as the pattern of branching in the nonarcading portion of the arteriolar network in skeletal muscle. The exteriorized cat sartorius muscle was used as the experimental model. The intravascular fluorescence of fluorescein isothiocyanate (FITC)-labeled Dextran 150 was observed with a low-light-level video camera, and the vascular networks were mapped. Arteriolar lengths and diameters were measured, and vessel position in the network was characterized by Strahler's method of ordering, in which the first-order arterioles give rise to most of the capillaries. Typically, the nonarcading, terminal networks contain three or four arteriolar orders. The sequences of the number of vessels, mean diameter, and mean length for each order are accurately described by geometric progressions (Horton's law). The distribution of diameters within each order was rather narrow: typically two-thirds of the vessels fell within 20% of the mean value. The spread was reduced by half when vessels within a single network were considered. During vasodilation to a standard stimulus the relative dispersion of diameters increased modestly. The distribution of vessel lengths was broader than for diameters. Two-thirds of vessels of a single order fell within 50-75% of the mean. The spread was less within individual networks. The variability of vessel geometry and branching patterns was substantially less within a single network than for a population drawn from a group of networks.

Anatomy↗

Oral mucous membrane pemphigoid. A study of sixty-five patients.

Sixty-five patients with oral mucous membrane pemphigoid were examined, treated, and followed for a mean of 3.5 years. Seventy-two percent were women, and the mean age was 59 years. In most patients multiple oral sites were involved and the gingiva was affected in 94% of the patients. Seven patients had ocular lesions (symblepharon), and seven others had nasal, vaginal, or pharyngeal involvement. Persons with skin lesions (bullous form) were not included in this series. Topical and systemic anti-inflammatory/immunosuppressive medications were successful in controlling signs and symptoms. There were no spontaneous remissions. Candidiasis, tobacco, other diseases, and drugs did not appear to be related to the pemphigoid.

Adult↗

Nucleotide sequence of a portion of the Autographa californica nuclear polyhedrosis virus genome containing the EcoRI site-rich region (hr5) and an open reading frame just 5' of the p10 gene.

The nucleotide sequence of a 1587 bp region lying within the HindIII-Q fragment of Autographa californica multiple nucleocapsid nuclear polyhedrosis virus (AcMNPV) DNA has been determined. It begins in the EcoRI-S-EcoRI-X region, continues to the HindIII-P/Q boundary and contains an open reading frame that codes for a polypeptide of 240 amino acids (p26). This open reading frame is also included in the 1100 and 1500 base transcripts previously mapped to this region. The sequence reveals that the 5' ends of the 1100 and 1500 base transcripts are located 20 bp downstream from the end of a putative TATA box (TAATTAAAT) and 19 bp upstream from the translation start codon (ATG) of the p26 open reading frame. The translation termination codon (TAA) falls in the immediate 5' flanking region of the major late p10 gene of AcMNPV, 3 bp downstream from the putative TATA box. The probable polyadenylation site for the 1100 base transcript lies 23 bp downstream from the cap site for the 750 and 2500 base transcripts encoding the p10 protein. The 5' flanking region of the p26 open reading frame contains the EcoRI site-rich region, hr5, whose sequence is included here. The EcoRI site-rich region, hr5, consists of six imperfect tandem repeats of a sequence that includes the EcoRI recognition site. These direct repeats also include many inverted repeats.

Amino Acid Sequence↗

The design of a diet restricted in saturated very long-chain fatty acids: therapeutic application in adrenoleukodystrophy.

Adrenoleukodystrophy is an inherited, progressive disorder of the CNS white matter and adrenal glands, associated with the pathognomonic accumulation of saturated very long-chain fatty acids, particularly C26:0. It has been previously demonstrated that the fatty acids that accumulate in adrenoleukodystrophy are, at least in part, of dietary origin. This observation, coupled with success of dietary phytanic acid restriction in a related disorder, Refsum's disease, encouraged us to develop a diet that would restrict dietary C26:0 intake. We report here the very long-chain fatty acids content of 135 common foods and development of a diet that restricts C26:0 intake to 3 mg, compared to 12 to 40 mg in the standard American diet. To limit C26:0 intakes it was found necessary to restrict fatty foods and the outer coverings of vegetables and fruits. In contrast to the success of phytanic acid restriction in limiting disease progress in Refsum's patients, administration of the very long-chain fatty acid-restricted diet to seven adrenoleukodystrophy patients for 3- to 24-month periods was found to be ineffective in lowering their plasma very long-chain fatty acids or in improving clinical status. Recently endogenous synthesis of C26:0 has been demonstrated and this may account for the failure of dietary therapy in adrenoleukodystrophy. It is possible that dietary restriction may augment other therapies in the future.

Adrenoleukodystrophy↗

Chromosome analysis of isolated colony erythroblasts in chronic myelogenous leukaemia.

To isolate and karyotype the progeny of erythroid progenitors, we applied colony erythroblasts derived from plasma clot marrow cultures from two healthy adults and two patients with newly diagnosed Ph1+ chronic myelogenous leukaemia (CML) to discontinuous Stractan density gradients. Erythroid colony proliferation by patient cells was increased relative to that of normal donor cells (P less than 0.01). 'Endogenous' colonies appeared in patient but not in normal donor marrow cultures. Greater than 95% of nucleated cells equilibrating at rho greater than or equal to 1.071 were basophilic proerythroblasts. While analysis of chromosome spreads of normal donor cells in this fraction showed normal karyotypes, cells from patient marrow cultures were Ph1+, whether cultured in the presence or absence of added erythropoietin. These findings suggest that chromosome abnormalities of erythroid progenitors may be expressed by their progeny in tissue culture, and that Stractan may be a useful supporting medium for separating colony erythroblasts for chromosome analysis.

Adult↗

The primary sequence of rabbit alpha-globin mRNA.

The rabbit alpha-globin DNA insertion in the chimeric plasmid pHb 72 (Liu et al., 1977) has been sequenced by the method of Maxam and Gilbert (1977). This has enabled us to determine the messenger RNA(mRNA) sequence beginning in the 5' untranslated region 9 nucleotides before the initiation codon and extending through the first 361 nucleotides of the translated region. The data reported here overlap and are in complete agreement with sequences determined by Baralle (1977) for the 5' end of the mRNA and by Proudfoot et al. (1977) for the 3' end. Our sequence is also in agreement with the partial complementary RNA (cRNA) sequencing data which we reported previously (Paddock et al., 1977), this work marks the completion of the primary sequence of the rabbit alpha-globin mRNA. These observations reaffirm the high fidelity with which gene copies can be synthesized in vitro, cloned in a bacterial plasmid and maintained in the host. The general features of the mRNA nucleotide sequence are duscussed with particular attention given to the base composition and codon preferences observed and to comparison of this sequence with other completed mRNA gene sequences. A new computer program has been used to search for the most stable base-pairing arrangement of the completed mRNA.

Amino Acid Sequence↗