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Biomedical subjects

A Li

Publications and source records attributed to A Li.

At least 361 records · Page 20Linked to original sources
PubMed1987

Molecular characterization of beta-thalassemia major and beta-thalassemia intermedia in China and Southeast Asia.

We have studied the spectrum of mutations producing beta-thalassemia (beta-thal) in South China and Southeast Asia in two groups of patients. In randomly selected patients with beta-thal major we characterized 78 beta-thal genes. In patients with beta-thal intermedia, 22 beta-thal genes were studied. The relevant mutation was characterized in all 78 genes of the first group, and 21 of 22 (96%) of mutant genes in the second group. Eight point mutations were found among the 100 genes studied. Of these eight alleles, four constituted 90% of the total. Prenatal diagnosis of beta-thalassemia in this region should be feasible by simplified techniques for direct detection of point mutations.

Asia, Southeastern↗
PubMed1986

Elevation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) polychlorinated biphenyls. Structure-activity relationships.

Administration of the commercial polychlorinated biphenyl (PCB) Aroclor 1254 to immature male Wistar rats resulted in increased levels (80-110%) of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) hepatic cytosolic receptor protein which remained elevated for 14 days. The effects of structure on the activity of individual PCB congeners to modulate hepatic cytosolic receptor levels were compared to the structure-activity relationships (SARs) which have been developed previously for PCBs as inducers of hepatic microsomal monooxygenases. 3,3',4,4'-Tetra- and 3,3',4,4',5-pentachlorobiphenyl induced the cytochrome P-448-dependent monooxygenase, ethoxyresorufin O-deethylase (EROD), and resembled 3-methylcholanthrene in their mode of monooxygenase enzyme induction. These congeners also bound to the receptor protein; however, neither compound increased hepatic cytosolic receptor protein levels. Several PCB congeners which exhibit low binding affinities for the cytosolic receptor protein resembled phenobarbitone (PB) in their mode of monooxygenase enzyme induction and, like PB, elevated cytosolic receptor protein levels. Nevertheless, a comparison of the time course of monooxygenase enzyme induction and receptor protein elevation by 2,2',4,4',5,5'-hexachlorobiphenyl and PB illustrated significant differences in their activities. PB-mediated elevation of receptor levels was maximized 24 hr after the last dose, and 48 hr later the receptor levels decreased to control values. In contrast, 5 days after administration of a single dose of 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumoles/kg) the receptor levels were elevated significantly, and these increased levels (205-127% increases over control) persisted for 14 days. There was no correlation between increased levels of hepatic receptor protein and the induction of the cytochrome P-450-dependent monooxygenases, aldrin epoxidase or 4-dimethylaminoantipyrine N-demethylase. Two PCBs, 2,3,3',4,4',5- and 2,2',3,4,4',5-hexachlorobiphenyl, which resembled Aroclor 1254 in their mode of monooxygenase enzyme induction, also elevated hepatic receptor protein levels but were less active than the PB-type inducers. Thus, the SARs developed for PCBs which elevate cytosolic receptor levels demonstrate that the most active compounds exhibit the lowest affinity for the receptor protein and do not induce EROD. In contrast, the more toxic PCB congeners which are approximate isostereomers of 2,3,7,8-TCDD both induced EROD and bound with high affinity to the receptor protein but did not increase hepatic cytosolic receptor protein levels.

Animals↗
PubMed1986

Dynamic changes of lung lymph flow and the release of lysosomal enzyme from the lungs after severe steam inhalation injury in goats.

Chronic lung lymph fistulae were produced in six goats according to Winn's and Stothert's methods with our modification to define the pathophysiology of pulmonary oedema after severe steam inhalation injury. Arterial blood gas, lung lymph flow (QLym), lymph/plasma total protein concentration ratio (L/P), and beta-glucuronidase (beta-G) in plasma and lung lymph were monitored for 24 h post-injury. The pathological changes in the lung tissues were also determined at the end of the study. It was found that directly after injury, QLym increased steadily to a peak value at 6 h, followed by declining values at 18 and 24 h. L/P decreased promptly during the 60 min after injury and then also steadily increased to a peak value at 4 h (P less than 0.05). A significant increase in plasma beta-G was only observed at 4 h post-burn. However, lung lymph beta-G activities and lymph beta-G transport increased immediately after injury, reaching a peak at 4 h (5 and 12 times above baseline values, respectively, P less than 0.01). Significant hypoxaemia and hypocapnia occurred at 2 h post-burn and deteriorated progressively throughout the study. There were obvious pulmonary interstitial and alveolar oedema microscopically. This study demonstrates that the increase in transvascular fluid and protein flux after steam inhalation injury is mainly due to increased pulmonary microvascular permeability. Nevertheless, a hydrostatic pressure effect can not be completely excluded, especially in the first hour post-burn. Lysosomal enzyme release is considered to be one of the important factors which damage lung microvascular elements and induce an increase in their permeability.

Animals↗
PubMed1985

Antagonist actions of bicuculline methiodide and picrotoxin on extrasynaptic gamma-aminobutyric acid receptors.

The effects of picrotoxin and bicuculline methiodide to block depolarizing responses of extrasynaptic receptors for gamma-aminobutyric acid (GABA) are compared using excitability testing of myelinated axons in amphibian peripheral nerve. The actions of the antagonists appear both complex and dissimilar. Picrotoxin (10-1000 microM) produces large reversible depressions of the maximal response to GABA (0.01-10mM) and increases the EC50 from 0.33 to 12.6 mM. With high concentrations of agonist and antagonist an insensitive component is apparent. The action of picrotoxin is not classically noncompetitive: it may represent a mixed antagonism (competitive and noncompetitive) or a noncompetitive one, masked by the presence of receptor reserve and (or) secondary depolarizing influences (e.g., GABA-evoked [K+] o accumulation). Bicuculline methiodide (10-200 microM) shifts the GABA concentration-response curve to the right; maximal responses persist and are even enhanced. The impression that bicuculline methiodide has a competitive action is supported by analysis of its inhibition of responses to low concentrations of the agonist. It is suggested that the enhancement of GABA responses by bicuculline methiodide and their apparent resistance to block by picrotoxin may be due to a common secondary effect of the antagonists such as a decrease in membrane conductance to K+ and (or) block of transmitter uptake.

Animals↗
PubMed1984

beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects.

To perform a systematic analysis of beta-thalassemia genes among Chinese, we have determined the DNA haplotype in the beta-globin gene region of 37 Chinese beta-thalassemia chromosomes. Only four haplotypes were found. Blot hybridization analysis of erythroid RNA from patients homozygous for haplotypes 1, 2, and 3 demonstrated different patterns, suggesting that a different mutation was associated with each haplotype. The mutation associated with haplotype 1 was a C----T substitution at IVS-2, position 654. This mutation produces a new donor splice site and leads to formation of a beta-globin RNA with an insertion of 73 nucleotides. The mutation associated with haplotype 2 was a nucleotide insertion of A between codons 71 and 72, which results in a frameshift and premature termination of beta-globin synthesis. Haplotype analysis suggests that these two mutations may account for up to 85% of beta-thalassemia genes in this ethnic group. The haplotype 3 gene contained a transcriptional "TATA" box mutation that has been previously reported. Oligonucleotide hybridization demonstrated that the mutation associated with haplotype 4 was the same IVS-1 position 5 substitution commonly observed among beta-thalassemia genes in Asian Indians. Since haplotype 4 of Chinese differs at polymorphic sites on either side of the IVS-1 position 5 mutation from the haplotype associated with this mutation in Indians, the mutation presumably arose independently in these two populations.

China↗
PubMed1978

Comparative study of ten bacteriocins of Clostridium perfringens.

Bacteriocins of Clostridium perfringens were prepared by ammonium sulfate precipitation of supernatant broth from 10 bacteriocinogenic strains. These bacteriocins were compared with respect to their ability to produce spheroplasts in a sensitive indicator strain; their inducibility; sensitivity to pH, proteolytic enzymes, and boiling; and their effect on macromolecular synthesis. Two bacteriocins were stable over a wide range of pH values and resisted boiling, and three bacteriocins were resistant to trypsin. Five bacteriocins shut down DNA, RNA, and protein synthesis; three bacteriocins had varying effects on DNA and RNA synthesis; and two bacteriocins had little effect on macromolecular synthesis. Antiserum prepared against one bacteriocin highly neutralized three bacteriocins with partial neutralization of five others; two bacteriocins were unaffected. Mutant strains selected for resistance to bacteriocin 28 also demonstrated coresistance to two other closely related bacteriocins and partial resistance to five others.

Bacteriocins↗
PubMedDate not supplied

A photometric method to analyze induced erythrocyte shape changes.

In this paper, a photometric method was introduced to quantify biochemically-induced red blood cell (RBC) shape changes when no shear force was acting on the cells. To obtain the photometric RBC shape parameter (RF1), a monolayer of point-attached RBCs was prepared on the floor of a flat flow chamber and the transmission of light perpendicular to the monolayer plane was measured: 1) in phosphate buffered saline with 0.1% bovine serum albumin (PBS+) and 2) in PBS+, containing a shape changing compound (in both, the RBCs were not deformed due to shear flow). To normalize the data, a third transmission value at a shear stress of 3 Pa was measured in PBS+ from the same RBC monolayer. To validate the photometric data, RF1 of RBCs exposed to shape changing agents was correlated by linear regression analysis with 1) data obtained with the tangent-counting technique (TC) and 2) the morphological index (MI). The coefficient of correlation was calculated at 0.95 for the TC data and 0.94 for the MI data, respectively. The sensitivity of the photometric method was tested with stomatocytogenic chlorpromazine (CP) and echinocytogenic sodium salicylate (SA). CP (2.5 microM) induced a significant decrease of RF1 to -0.045 (N = 6 donors, p < 0.01), whereas SA (2.5 mM) increased RF1 to +0.027 significantly (N = 6, donors, p < 0.01). Both the CP-induced and the SA-induced shape changes appeared less than 2 min after application of the shape changing agents, and changed gradually within another 30 min when the agent was present in PBS+, partly disappearing within about 2 min after reincubation of the shape transformed RBCs in PBS+ not containing the agent.

Adult↗
PubMedDate not supplied

Phrenic response to hypercapnia in the unanesthetized, decerbrate, newborn rat.

We developed a decerebrate, vagotomized, newborn rat preparation to investigate brainstem respiratory control mechanisms without the influence of anesthesia, supra-pontine structures, or vagally mediated feedback mechanisms. We measured the changes in phrenic nerve electrical activity in response to breathing 3% and 5% CO2 in unanesthetized, vagotomized, decerebrate newborn rats from 0 to 10 days of age and compared them with the changes in anesthetized, vagotomized, newborn rats and adult, vagotomized, decerebrate or anesthetized, animals. Phrenic nerve activity was irregular in the young newborn rats and became more regular between 7 and 10 days of age. T1 and T1/Ttot increased with age but increasing age had no influence on the response to CO2. The response to CO2 was dominated by increases in phrenic amplitude, minute activity, and inspiratory slope with no change in timing variables. These responses are similar to those that have been reported previously in vagally intact animals, suggesting that vagal feedback contributes little to the response to hypercapnia in the newborn rat. In summary, decerebrate newborn rats consistently respond to hypercapnia by increasing inspiratory drive similar to conscious animals.

Animals↗