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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 595 records · Page 33Linked to original sources

A pressurized injection/suction system for ventilation in the presence of complete airway obstruction.

OBJECTIVE: To describe the design and ventilatory characteristics of a new mode of ventilation (pressurized injection/suction ventilation). DESIGN: Descriptive and analytical laboratory study. SETTING: Laboratory study. SUBJECTS: Simulated lung model and dogs. INTERVENTIONS: We tested the ability to maintain ventilation through a 2.5-mm internal diameter ventilating stylet in the setting of simulated complete airway occlusion. A microprocessor-controlled ventilator mode was used wherein injection of oxygen under high pressure (flow rate 95 L/min) alternates with suction of expired gas (flow rate 18 L/min) through the ventilating stylet. MEASUREMENTS AND MAIN RESULTS: In a lung model, we achieved a maximum minute ventilation of 12.9 L/min. In two dogs, we maintained stable oxygenation (mean PaO2 603 +/- 47 torr [80.4 +/- 6.3 kPa]) and ventilation (mean PaCO2 19 +/- 3 torr [2.5 +/- 0.4 kPa]) for 15 mins at maximum minute ventilation settings. No clinically important deleterious effects on the tracheal mucosa were observed. The ventilator system's safety-abort feature prevented overinflation or excessive deflation of the dogs' lungs in every test of simulated malfunction of the pressure-monitoring mechanism. CONCLUSIONS: Pressurized injection/suction ventilation can maintain adequate gas exchange in an animal model with near-complete airway obstruction. Further work is needed to develop the safety and clinical applications of pressurized injection/suction ventilation in the management of patients with near-complete airway occlusion.

Airway Obstruction↗

Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation. A randomized controlled trial.

We performed a prospective randomized, double-blind study to assess the efficacy of selective depletion of CD8+ bone marrow cells in preventing acute graft-versus-host disease (GVHD) in 38 patients undergoing HLA-identical sibling donor bone marrow transplantation for leukemia. All patients received CsA for GVHD prophylaxis. Nineteen patients received marrow depleted of CD8+ cells by ex vivo treatment with anti-leu2, an anti-CD8 mAb and complement; four patients had moderate (grade 1 or 2 acute GVHD) and the only patient who experienced grade 3 manifestations was a technical failure. The control group consisted of 19 patients who received unmodified bone marrow; one patient had grade 1, 4 patients had grade 2, and 10 had grade 3 or 4 acute GVHD. The actuarial incidence of grade > or = 2 acute GVHD was 20 +/- 20% in the CD8-depleted group compared with 80 +/- 18% in the controls (P = 0.004). Death in 5 of the control patients and the single patient in whom CD8 depletion was a technical failure was related to acute GVHD. Graft failure occurred in 2 patients in the CD8-depleted group and in none of the controls. Leukemic relapse occurred in 2 patients receiving CD8-depleted bone marrow and 2 patients in the control group. Seven patients receiving marrow depleted of CD8+ cells are alive and free of leukemia and 9 patients in the control group are alive, 7 of whom remain leukemia-free (P = 0.88). The 3-year actuarial leukemia-free survival is 37 +/- 22% of the CD8-depleted group and 36 +/- 22% for the control group. These results indicate that selective depletion of CD8+ cells from the bone marrow significantly reduces the incidence and severity of acute GVHD.

Adolescent↗

The crying pattern of Korean infants and related factors.

In a study of 160 Korean infants aged between one and six months, average time spent sleeping decreased, and total daily maternal periods of contact increased, with age (though not significantly). The increment of total periods spent by the infant alone was significant, but the decrease of crying duration was not. There was no definite clustering of crying during the evening hours. The most common responses of mothers towards their baby's crying were feeding, contact and no response, in order of frequency. Compared with Western studies, the duration of crying of Korean infants was shorter and the time of holding and/or close contact with mothers longer, and colic was not found in this study. These findings may be related to the caring practice of mothers.

Age Factors↗

Mg(2+)-dependent inhibition of KATP by sulphonylureas in CRI-G1 insulin-secreting cells.

1 Patch-clamp recording techniques were used to examine the effects of tolbutamide, glibenclamide, meglitinide and thiopentone on KATP in CRI-GI insulin-secreting cells in the presence and absence of Mg2+. 2 In the absence of Mg2+ in the intracellular bathing solution, tolbutamide was significantly less effective when applied either to the intracellular or to the extracellular surfaces of cell-free patches. Removal of extracellular Mg2+ did not alter the effectiveness of tolbutamide provided that Mg2+ was present at the intracellular surface of the patch. 3 Tolbutamide was also significantly less effective when applied to the intracellular surface of cell-free patches when Mn2+ was used as a replacement for Mg2+. 4 Both the sulphonylurea, glibenclamide and the non-sulphonylurea derivative, meglitinide also showed Mg2+ dependent inhibitory effects in cell-free patches. In contrast, the barbiturate thiopentone inhibited KATP in a Mg(2+)-independent manner. 5 Whole-cell IK(ATP) were used to quantify the effects of tolbutamide and glibenclamide in the presence and absence of intracellular Mg2+. Concentration-inhibition curves, in the presence of intracellular Mg2+, resulted in IC50 values of 12.1 microM and 2.1 nM for tolbutamide and glibenclamide, respectively. In the absence of intracellular Mg2+, the corresponding IC50 values were 25.3 mM and 3.6 microM, respectively. The values of IC50 for thiopentone in the presence and absence of intracellular Mg2+ were 69.4 microM and 69.2 microM, respectively. 6 With respect to the high affinity binding sites for [3H]-glibenclamide in CRI-G1 membranes, no significant differences were found between the dissociation constants for, or the maximal binding capacities of, [3H]-glibenclamide in the presence or absence of Mg2+. 7. In the CRI-G1 insulin-secreting cell line, it is concluded that intracellular Mg2+ does not influence the affinity of the sulphonylureas for the sulphonylurea receptor but that this ion is critically important for the interaction between the sulphonylurea receptor and KATP.

Adenosine Triphosphate↗

Adults with acquired hearing loss: identification and referral patterns of community health workers.

Community health workers in one health region of New South Wales were surveyed about their criteria and referral patterns to identify and assist adults with acquired hearing losses. Reported or observed communication problems were the most commonly used criteria for identifying hearing loss, suggesting that a failure model was being utilised. Given that the literature has previously demonstrated reluctance on the part of individuals with acquired hearing loss to report their hearing difficulties, the implications of these results are discussed. Clients suspected of having acquired hearing losses were usually referred to their doctors for further investigation and treatment. Other hearing help services were not systematically utilised. Alternative strategies for identifying and managing acquired hearing loss at the community level are needed.

Community Health Workers↗

Regiospecific and stereoselective hydroxylation of 1-indanone and 2-indanone by naphthalene dioxygenase and toluene dioxygenase.

The biotransformation of 1-indanone and 2-indanone to hydroxyindanones was examined with bacterial strains expressing naphthalene dioxygenase (NDO) and toluene dioxygenase (TDO) as well as with purified enzyme components. Pseudomonas sp. strain 9816/11 cells, expressing NDO, oxidized 1-indanone to a mixture of 3-hydroxy-1-indanone (91%) and 2-hydroxy-1-indanone (9%). The (R)-3-hydroxy-1-indanone was formed in 62% enantiomeric excess (ee) (R:S, 81:19), while the 2-hydroxy-1-indanone was racemic. The same cells also formed 2-hydroxy-1-indanone from 2-indanone. Purified NDO components oxidized 1-indanone and 2-indanone to the same products produced by strain 9816/11. P. putida F39/D cells, expressing TDO, oxidized 2-indanone to (S)-2-hydroxy-1-indanone of 76% ee (R:S, 12:88) but did not oxidize 1-indanone efficiently. Purified TDO components also oxidized 2-indanone to (S)-2-hydroxy-1-indanone of 90% ee (R:S, 5:95) and failed to oxidize 1-indanone. Oxidation of 1- and 2-indanone in the presence of [18O]oxygen indicated that the hydroxyindanones were formed by the incorporation of a single atom of molecular oxygen (monooxygenation) rather than by the dioxygenation of enol tautomers of the ketone substrates. As alternatives to chemical synthesis, these biotransformations represent direct routes to 3-hydroxy-1-indanone and 2-hydroxy-1-indanone as the major products from 1-indanone and 2-indanone, respectively.

Biotransformation↗

Cloning and characterization of the socA locus which restores development to Myxococcus xanthus C-signaling mutants.

The csgA gene produces an intercellular signal during fruiting body formation of the myxobacterium Myxococcus xanthus. Sporulating pseudorevertants were isolated to allow us to understand the mechanism by which CsgA is perceived by cells and used to regulate developmental gene expression. Two strains, LS559 and LS560, which have closely linked transposon insertions, soc-559 (formerly csp-559) and soc-560 (formerly csp-560), respectively, regained all the developmental behaviors lost by the csgA mutation including the ability to ripple, form fruiting bodies, and sporulate. The sequence analysis of the socA locus revealed that there are three putative protein-coding regions, designated socA1, socA2, and socA3. The deduced amino acid sequence of socA1 exhibits characteristics of the short-chain alcohol dehydrogenase family. The deduced amino acid sequence of socA2 shares 48% identity with the frdD gene product of the frd operon in Proteus vulgaris which anchors fumarate reductase to the membrane. The deduced amino acid sequence of socA3 does not show homology to any known proteins. Genotypic complementation, Northern (RNA) blotting, DNA sequence analysis, and the pattern of gene expression all suggest that these three genes are polycistronic. Since the socA mutations effectively bypass CsgA, the question of why csgA is maintained in M. xanthus was examined by studying the long-term stability of socA spores. Unlike the wild type, socA mutant spores germinated on starvation agar. Transmission electron micrographs of spore thin sections revealed that germination is not due to an obvious structural deficiency of the socA spores. These results suggest that the ability of socA myxospores to survive long periods under unfavorable environmental conditions is severely comprised. Therefore, soxA appears to be essential for the development of M. xanthus.

Amino Acid Sequence↗

Erythroid expression of the heme-regulated eIF-2 alpha kinase.

The role of heme-regulated eIF-2 alpha kinase (HRI) in the regulation of protein synthesis in rabbit reticulocytes is well documented. Inhibitors of protein synthesis with properties similar to those of HRI have been described in some nonerythroid cell types, but it has not yet been determined whether these eIF-2 alpha kinase activities are mediated by HRI or one or more as yet uncharacterized kinases. We have studied the expression of mRNA, polypeptide, and kinase activities of HRI in various tissues from both nonanemic and anemic rabbits. Our results indicate that HRI is expressed in an erythroid cell-specific manner. HRI is present in the bone marrow and peripheral blood of both nonanemic and anemic rabbits but not in any of the other tissues tested. HRI mRNA is present at low levels in uninduced mouse erythroleukemic (MEL) cells and human K562 cells and accumulates to higher levels upon induction. The accumulation of HRI mRNA in differentiating MEL cells is dependent upon the presence of heme. The addition of 3-amino-1,2,4-triazole (AT), an inhibitor of heme biosynthesis, to the induction medium markedly reduced HRI mRNA accumulation. Simultaneous addition of hemin and AT to the dimethyl sulfoxide induction medium largely prevented the inhibition of HRI mRNA induction by AT. These findings indicate that HRI is expressed in an erythroid cell-specific manner and that the major physiologic role of HRI is in adjusting the synthesis of globins to the availability of heme.

Anemia↗

Parathyroid hormone induces sequential c-fos expression in bone cells in vivo: in situ localization of its receptor and c-fos messenger ribonucleic acids.

Localization of PTH/PTH-related peptide (PTH/PTHrP) receptor mRNA and PTH induction of c-fos expression were examined in bones of 4-week-old rats by in situ hybridization. Receptor transcripts were most highly expressed by growth plate chondrocytes from lower proliferating to upper hypertrophic cell layers. PTH/PTHrP receptor mRNA also was expressed in osteoblasts as well as in some bone marrow stromal cells. Subcutaneous administration of human PTH-(1-84) (225 micrograms/kg) induced rapid, transient, and sequential expression of the protooncogene c-fos mRNA in cells in bone. Osteoblasts and chondrocytes expressing PTH/PTHrP receptor transcripts as well as some stromal cells expressed c-fos mRNA first (15-60 min), followed by transient expression in the majority of stromal cells and in osteoclasts (1-2 h). Delayed and transient induction of c-fos in cells with few or no detectable receptor transcripts suggests that PTH acts indirectly on stromal cells and osteoclasts by either stimulating osteoblasts to secrete a substance(s) that acts locally and/or inducing changes in cell-cell contacts between osteoblasts and adjacent cells.

Animals↗

Estradiol and progesterone production by cultured granulosa cells cryopreserved from in vitro fertilization patients.

Gonadotropin-stimulated steroidogenesis was studied in cultured human granulosa-lutein cells obtained from patients undergoing procedures for in vitro fertilization. The impact of cryopreservation on cell function in vitro was studied. Granulosa cells obtained from in vitro fertilization patients were cultured in serum-supplemented medium or cryopreserved at -135 degrees C for 2-22 months. Fresh (unfrozen) cells (10(5) produced estradiol at a rate of 1320 pmol/l (over 72 h) and progesterone at about 2500 nmol/l. Estradiol production by either fresh or cryopreserved granulosa cells in culture was unaffected by physiological concentrations of follicle-stimulating hormone (7 IU/l). Adding testosterone (10(-7) mol/l) to the medium increased estradiol secretion approximately sixfold. In contrast, progesterone production was not affected by follicle-stimulating hormone or testosterone. No significant differences were observed in cultures of cryopreserved granulosa cells compared to cultures of unfrozen cells with respect to estradiol secretion, the effects of follicle-stimulating hormone or testosterone on estradiol secretion, or progesterone production. Progesterone production by fresh and cryopreserved cells was stimulated by human chorionic gonadotropin. These data indicate that cryopreservation offers the potential to facilitate prospective studies utilizing large numbers of human granulosa-lutein cells in culture.

Aromatase↗

Comparative metabolism of SC-42867 and SC-51089, two PGE2 antagonists, in rat and human hepatocyte cultures.

1. The metabolism of SC-42867 and SC-51089, two PGE2 antagonists, was studied in cultured rat and human hepatocytes. Both compounds possess an 8-chlorodibenzoxazepine moiety, but differ from each other by the nature of the side chain connected to the nitrogen atom. SC-42867 and SC-51089 and their in vitro metabolites were separated by reversed-phase hplc. The major metabolites of both compounds were identified by mass spectrometry (ms) analysis. 2. SC-42867 was metabolized on the tricyclic moiety only. Oxidative N-dealkylation with opening of the oxazepine ring was the major metabolic pathway obtained in rat hepatocytes. The metabolic profile obtained in cultured human hepatocytes was comparable with that of cultured rat hepatocytes. However, the compound was metabolized to a much lower extent by the human cells. 3. SC-51089 was extensively metabolized by both cultured rat and human hepatocytes. Human cells metabolized this compound quite differently than cultured rat hepatocytes. Aromatic hydroxylation with consequent glucuronidation and sulphation were the main metabolic pathways observed in cultured human hepatocytes. Oxidative N-dealkylation with opening of the oxazepine ring and consequent glucuronidation was the major metabolic pathway observed in rat hepatocytes. Further metabolism occurred, in contrast with the human hepatocytes, mainly on the side chain. 4. The present in vitro results are compared with data of previous in vivo studies performed in rat.

Adult↗

Antimicrobial susceptibility of Campylobacter fetus subsp. fetus isolated from blood and synovial fluid.

Campylobacter fetus subsp. fetus is a rare human pathogen, but can cause serious extraintestinal infections. Effective antimicrobial agent is required for the therapy, but we have very limited knowledge on the susceptibility of the organism. In this study, the susceptibility of 25 isolates of the organism to 14 antimicrobial agents was tested by an agar dilution method. Antimicrobial agents with low MIC ranges, in micrograms/ml, were: meropenem < or = 0.25, dirithromycin < or = 0.5, gentamicin < or = 1, amikacin, ofloxacin, tetracycline and erythromycin < or = 2. The MIC range of cefepime was 0.5-8 micrograms/ml, but those of other beta-lactams were relatively high. All of the isolates were interpreted to be susceptible to cefepime, meropenem, amikacin, gentamicin, ofloxacin, tetracycline and dirithromycin. A significant proportion of the isolates were either intermediate or resistant to ampicillin, cephalothin, cefotaxime, aztreonam, loracarbef and erythromycin. In conclusion, the organism remains susceptible to aminoglycosides and tetracycline. Greater in vitro activity of meropenem, ofloxacin and dirithromycin require clinical evaluation.

Anti-Bacterial Agents↗

Determinations of personal carbon monoxide exposure and blood carboxyhemoglobin levels in Korea.

Determinant factors for personal carbon monoxide (CO) exposures were sought in Korea, where CO poisoning has been a major public health problem due to coal briquette (Yeontan) combustion for space heating and cooking. Personal 24-hr CO exposures of 15 housewives were measured by CO passive samplers on 2 days of the week (Wednesday and Sunday). Blood samples were taken to measure carboxyhemoglobin (COHb) just after the exposure sampling. Average CO exposure and COHb level were 5.6 ppm and 2.4%, respectively. Personal CO exposures as well as COHb levels were significantly increased by the use of Yeontan, especially on a weekday. Carboxyhemoglobin levels were closely related to the time between blood collection and replacement of Yeontan: the closer the blood collection was to replace Yeontan, the higher the COHb levels were. Assuming a background COHb of 1.34%, COHb increased on average by 1.8% with a 24-hr personal CO exposure of 10 ppm. The relationship between CO exposure and COHb level was provided by simultaneous direct measurements in real environment, although a measurement of COHb at the end of exposure could not represent previous 24-hr exposure thoroughly.

Adult↗

[Mode of action of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) in target organs].

Calcium and phosphorus metabolism is mainly regulated by PTH through its actions on kidney and bone. PTHrP, which is associated with the hypercalcemia of malignancy syndrome, binds to and activates the same receptor that PTH does. cDNA clones of PTH/PTHrP receptors from rat osteosarcoma (ROS 17/2.8) and opossum kidney (OK) cells are highly homologous and are members of a novel G protein-linked receptor family that includes calcitonin, glucagon, GLP-1, GHRH, VIP, and secretin receptors. Analysis of the protein sequence predicts a receptor with 7 transmembrane domains, a 155 amino acids (aa) extracellular (EC) N-terminal, and 130aa intracellular C-terminal domaina. The extracellular domain has 6 conserved cysteines and 4 potential glycosylation sites. When transfected in COS cells, both receptors are able to bind PTH and PTHrP active fragments with equal affinity. Likewise, agonists activate both adenylate cyclase and phospholipase C efficiently. The N-terminal EC domain and the first EC loop seem to determine the receptor binding capacity with the agonists. Activation of adenylate cyclase and phospholipase C might involve multiple sites between the 3rd helix and the C-terminal tail. Partial characterization of the rat PTH/PTHrP receptor gene demonstrates the existence of at least 15 exons. The first six transmembrane domains are encoded by separated exons. The PTH/PTHrP receptor mRNA is expressed mainly in kidney and bone, and also is widely expressed in many tissues, but not all. A major 2.3-2.5 kb transcript is observed in all these tissues. Nevertheless, 2 larger transcripts are observed in kidney and liver, and multiple smaller mRNA species are observed in kidney, skin, and testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗