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Biomedical subjects

Y Lee

Publications and source records attributed to Y Lee.

At least 397 records · Page 22Linked to original sources
PubMed1994

Effect of corticosterone on the enhancement of the acoustic startle reflex by corticotropin releasing factor (CRF).

The present study evaluated the effects of adrenalectomy and chronic administration of corticosterone on the ability of CRF given intraventricularly to increase the amplitude of the acoustic startle reflex in rats. Experiment 1 showed that CRF-enhanced startle was not affected by adrenalectomy, indicating a central effect independent of the integrity of the hypothalamic-pituitary-adrenal axis. In Experiment 2, chronic injection of corticosterone augmented CRF-enhanced startle using a dose of CRF (0.25 micrograms) that normally is ineffective in increasing startle amplitude. Chronic injection of corticosterone by itself did not increase startle amplitude (Experiment 3). We suggest that the potentiation of CRF-enhanced startle by corticosterone may result from an activation of CRF in the central nucleus of the amygdala.

Acoustic Stimulation↗
PubMed1994

Excessive spinal cord toxicity from intensive central nervous system-directed therapies.

BACKGROUND: Intrathecal chemotherapy, radiation therapy, and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system (CNS) disease in hematologic malignancies. Twenty-three cases of myelopathy that occurred in patients who received intensive CNS-directed therapy were evaluated to identify the determinants of this severe CNS toxicity. METHODS: Nine cases treated by the authors and 14 collected from the literature are discussed. Twelve had Burkitt's leukemia/lymphoma. Patient ages ranged from 3 to 30 years (median, 15 years). The dose intensity of CNS-directed therapies, including intrathecal cytosine arabinoside (ara-C), intrathecal methotrexate (MTX), systemic high dose (HD) MTX, systemic HD ara-C, systemic thiotepa, and CNS radiation, was evaluated by the determination of single drug doses and cumulative total drug or irradiation doses over elapsed treatment durations. RESULTS: Central nervous system treatment was prophylactic in 10 cases; active CNS disease was being treated in 13 cases. One patient received only intrathecal ara-C before toxicity occurred; other received intrathecal ara-C and varying combinations of intrathecal MTX, HD ara-C, HD MTX, CNS radiation, and systemic thiotepa. Eight patients died of toxicity, of whom 6 had autopsy-proven cord necrosis; 3 were ventilator-dependent; 10 had persistent paraplegia or paraparesis; and 2 recovered completely. CONCLUSION: Both highly intensive, short CNS treatment sequences and lower intensity, long term cumulative treatments may result in this rare but severe myelopathy. The cause is multifactorial, with systemic chemotherapy, intrathecal chemotherapy, and radiation therapy contributing to toxicity. Multiple intrathecal ara-C and/or MTX doses given at frequent (daily) intervals should be avoided. Concurrent intrathecal ara-C and systemic HD ara-C also appear to be especially toxic. Intrathecal hydrocortisone given with intrathecal ara-C does not protect against myelopathy. Multiple, frequently spaced courses of CNS-directed therapies must be avoided, especially in patients who have received prior CNS radiation.

Adolescent↗
PubMed1994

Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships.

Hyperinsulinemia, loss of glucose-stimulated insulin secretion (GSIS), and peripheral insulin resistance coexist in non-insulin-dependent diabetes mellitus (NIDDM). Because free fatty acids (FFA) can induce these same abnormalities, we studied their role in the pathogenesis of the NIDDM of obese Zucker diabetic fatty (ZDF-drt) rats from 5 weeks of age (before the onset of hyperglycemia) until 14 weeks. Two weeks prior to hyperglycemia, plasma FFA began to rise progressively, averaging 1.9 +/- 0.06 mM at the onset of hyperglycemia (P < 0.001 vs. controls). At this time GSIS was absent and beta-cell GLUT-2 glucose transporter was decreased. The triacylglycerol content of prediabetic islets rose to 10 times that of controls and was correlated with plasma FFA (r = 0.825; P < 0.001), which, in turn, was correlated with the plasma glucose concentration (r = 0.873; P < 0.001). Reduction of hyperlipacidemia to 1.3 +/- 0.07 mM by pair feeding with lean littermates reduced all beta-cell abnormalities and prevented hyperglycemia. Normal rat islets that had been cultured for 7 days in medium containing 2 mM FFA exhibited increased basal insulin secretion at 3 mM glucose, and first-phase GSIS was reduced by 68%; in prediabetic islets, first-phase GSIS was reduced by 69% by FFA. The results suggest a role for hyperlipacidemia in the pathogenesis of NIDDM; resistance to insulin-mediated antilipolysis is invoked to explain the high FFA despite hyperinsulinemia, and sensitivity of beta cells to hyperlipacedemia is invoked to explain the FFA-induced loss of GSIS.

Adipocytes↗
PubMed1994

Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily.

We have identified a member of the steroid receptor superfamily and cloned it from human and rat hypothalamus, prostate, and testis cDNA libraries. The open reading frame between first ATG and terminator TGA can encode 615 (human) and 596 (rat) amino acids with calculated molecular mass of 67.3 (human) and 65.4 (rat) kDa. The amino acid sequence of this protein, called TR4 orphan receptor, is closely related to the previously identified TR2 orphan receptor. The high homology between TR2 and TR4 orphan receptor suggests that these two orphan receptors constitute a unique subfamily within the steroid receptor superfamily. These two orphan receptors are differentially expressed in rat tissues. Unlike TR2 orphan receptors, the TR4 orphan receptor appears to be predominantly located in granule cells of the hippocampus and the cerebellum, suggesting that it may play some role(s) in transcriptional regulation in these neurons.

Amino Acid Sequence↗
PubMed1994

Detection of two phospholipase A2(PLA2) activities in leaves of higher plant Vicia faba and comparison with mammalian PLA2's.

Leaves of higher plant Vicia faba contains two Phospholipase A2 (PLA2) activities which are detected in cytosolic fractions. Based on a gel filtration column chromatography, two cytosolic PLA2 activities migrated with molecular masses of 70 kDa and 14 kDa. The first (70 kDa peak) was optimally active at pH 4.5 and was not dependent on [Ca2+] for its activity. In the presence of 5 mM CaCl2, 'phospholipase B' activity was shown in the 70 kDa peak. The second (14 kDa peak) was optimally active in the pH range 9-10 and required millimolar concentrations of calcium for optimal activity. The two activities were not inhibited by dithiothreitol. Neither anti-pancreatic PLA2 antiserum nor anti-(pig spleen 100 kDa cytosolic PLA2) antiserum immunoprecipitated any activity of the two plant PLA2's. The present results indicate that at least the 14 kDa form of the two PLA2 enzymes detected in leaves of higher plants is biochemically and immunochemically different from the well characterized Ca(2+)-dependent mammalian PLA2's.

Animals↗
PubMed1994

Expression of scatter factor/hepatocyte growth factor is regionally correlated with the initiation of sperm motility in murine male genital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility?

Based upon findings that the scatter factor/hepatocyte growth factor (SF/HGF) has strong mitogenic and motogenic properties, and that the sperm cell acquires its fertilizing capacity and motility in the distal parts of mammalian epididymis, the present study was conducted to investigate the role of SF/HGF in initiation of sperm cell motility. This was investigated by determining the expression of SF/HGF in various regions of the murine male genital tract by scatter and cell tracking assays using MDCK epithelial cells, Western blot procedure, and the immunohistochemical procedure using paraffin sections of various regions of the male genital tract. The findings from all these assays indicate that SF/HGF is differentially expressed in various parts of the male genital tract with slight or no expression in the testes, caput epididymis, and vas deferens, and with the highest expression in cauda and corpus (distal) epididymis followed by expression in the corpus (proximal) epididymis. This region-specific SF/HGF expression pattern coincides with the pattern of acquiring the fertilizing capacity and motility by the sperm cell during its transit through the male genital tract. However, wherever SF/HGF was expressed in the male genital tract, its molecular weight was slightly higher (Mr, 82 kD), compared to the SF/HGF expressed in various other somatic tissues (Mr, 78 kD), indicating that the genital tract SF/HGF may be a different molecular species that shares some immunoreactive epitopes with the somatic cell SF/HGF. Incubation of immotile sperm from caput epididymis with the purified human placental SF/HGF of 78 kD initiated motility in 5-15% of sperm population. These results strongly suggest that the SF/HGF-like activity is expressed in the male genital tract in a region-specific manner, and this activity may have a role in initiation of sperm motility acquired during its transit through the epididymis in mammals.

Animals↗
PubMed1994

Factors affecting leakage following esophageal anastomosis.

Esophageal anastomotic leaks remain the most serious problem following extirpative procedures for esophageal carcinoma. We conducted a retrospective analysis of 352 patients with carcinoma in the thoracic esophagus who had undergone esophageal anastomosis following esophagectomy at the Kurume University Hospital between 1981 and 1990. Of these, 94 patients (27%) developed anastomotic leaks, and out of this subgroup, 21 (6%) died as a direct result of the leak. A further 20 patients (6%) underwent repair of the leak, after which they were able to tolerate oral intake. The anastomotic leak healed spontaneously in the other 53 patients (15%). The risk factors predisposing to leaks from esophageal anastomoses were determined as: (1) the anastomosis being performed via a retrosternal or subcutaneous route as opposed to an intrathoracic route, (2) the use of colonic interposition as opposed to a gastric pedicle, (3) performing a manual anastomosis as opposed to a mechanical anastomosis, and (4) employing an end-to-end anastomosis, as opposed to an end-to-side anastomosis, using a mechanical method. By introducing an anastomotic stapling device, a microvascular technique, a staged operation based on the preoperative risk analysis, and improvement in pre- and postoperative management, the incidence of anastomotic leakage could be decreased from 35% to 14%, and that of consequent hospital mortality, from 9% to 2%.

Adult↗
PubMed1994

Polyunsaturated fatty acids modulate stomatal aperture and two distinct K+ channel currents in guard cells.

Regulation of stomatal aperture is critical for both CO2 uptake and water retention by plants. Stomatal opening is produced by osmotic water flow into guard cells, which follows K+ transport across the plasma membrane. We report here that linolenic acid and arachidonic acid, but not several other fatty acids, enhance stomatal opening and inhibit stomatal closing. In patch clamped guard cell protoplasts, linolenic and arachidonic acid rapidly potentiated inward K+ currents and inhibited outward K+ currents, which are carried via distinct K+ channels. These results suggest that certain fatty acids regulate stomatal aperture by modulation of two different K+ channels and may act as second messengers for stimuli that regulate CO2 uptake and water retention by plants.

Carbon Dioxide↗
PubMed1994

Cobalt(II) Oxidation by the Marine Manganese(II)-Oxidizing Bacillus sp. Strain SG-1.

The geochemical cycling of cobalt (Co) has often been considered to be controlled by the scavenging and oxidation of Co(II) on the surface of manganese [Mn(III,IV)] oxides or manganates. Because Mn(II) oxidation in the environment is often catalyzed by bacteria, we have investigated the ability of Mn(II)-oxidizing bacteria to bind and oxidize Co(II) in the absence of Mn(II) to determine whether some Mn(II)-oxidizing bacteria also oxidize Co(II) independently of Mn oxidation. We used the marine Bacillus sp. strain SG-1, which produces mature spores that oxidize Mn(II), apparently due to a protein in their spore coats (R.A. Rosson and K. H. Nealson, J. Bacteriol. 151:1027-1034, 1982; J. P. M. de Vrind et al., Appl. Environ. Microbiol. 52:1096-1100, 1986). A method to measure Co(II) oxidation using radioactive Co as a tracer and treatments with nonradioactive (cold) Co(II) and ascorbate to discriminate bound Co from oxidized Co was developed. SG-1 spores were found to oxidize Co(II) over a wide range of pH, temperature, and Co(II) concentration. Leucoberbelin blue, a reagent that reacts with Mn(III,IV) oxides forming a blue color, was found to also react with Co(III) oxides and was used to verify the presence of oxidized Co in the absence of added Mn(II). Co(II) oxidation occurred optimally around pH 8 and between 55 and 65 degrees C. SG-1 spores oxidized Co(II) at all Co(II) concentrations tested from the trace levels found in seawater to 100 mM. Co(II) oxidation was found to follow Michaelis-Menten kinetics. An Eadie-Hofstee plot of the data suggests that SG-1 spores have two oxidation systems, a high-affinity-low-rate system (K(m), 3.3 x 10 M; V(max), 1.7 x 10 M . spore . h) and a low-affinity-high-rate system (K(m), 5.2 x 10 M; V(max), 8.9 x 10 M . spore . h). SG-1 spores did not oxidize Co(II) in the absence of oxygen, also indicating that oxidation was not due to abiological Co(II) oxidation on the surface of preformed Mn(III,IV) oxides. These results suggest that some microorganisms may directly oxidize Co(II) and such biological activities may exert some control on the behavior of Co in nature. SG-1 spores may also have useful applications in metal removal, recovery, and immobilization processes.

Journal Article↗
PubMed1994

Direct plasma radioimmunoassay for rat amylin-(1-37): concentrations with acquired and genetic obesity.

Amylin (islet-associated polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreatic beta-cell. Accurate measurement of its plasma levels is important for delineating the physiological range over which amylin acts. We describe a reproducible, highly specific, and sensitive radioimmunoassay for direct measurement of plasma amylin-(1-37). We measured changes in portal and systemic plasma amylin and insulin in three groups of anesthetized rats: lean young adult and old adult Wistar rats with acquired obesity, and Wistar fatty [WDF/TaFa (fa/fa)] rats, a model of genetic obesity and insulin resistance derived from the Wistar strain. Changes in response to fasting, feeding, and intravenous stimulation with glucose plus arginine were assessed. We find that the amylin-to-insulin ratio is constant in fasted or fed young and old rats because of proportionate increases in both entities with aging. In genetically obese Wistar rats, amylin and insulin levels are three- to tenfold higher than in lean young or obese old normal controls. Islet stimulation by feeding or intravenous glucose plus arginine resulted in a decreased amylin-to-insulin molar ratio in all groups. When normalized for the degree of islet stimulation, amylin-to-insulin ratios were significantly elevated in genetically obese vs. normal rats, both in the portal and systemic circulation. These results demonstrate that aging-related weight gain in normal rats is associated with moderate and proportional increases in amylin and insulin, whereas genetic obesity is characterized by elevated amylin and an increased amylin-to-insulin ratio. Implications for the pathogenesis of insulin resistance and obesity are discussed.

Aging↗
PubMed1994

[Anesthetic management of tetralogy of Fallot with absent pulmonary valve--a case report].

Tetralogy of Fallot is characterized by a VSD, overriding of the aorta, right ventricular hypertrophy, and pulmonary stenosis. Absence of the pulmonary valve occurs in 2.6-6% of patients with tetralogy of Fallot. Operative procedures to relieve respiratory symptoms have been described with an mortality of 35-100%. Respiratory compromise may be severe in these infants secondary to bronchial compression by the aneurysmally dilated pulmonary arteries and present a different hemodynamic profile than those with classic tetralogy of Fallot. An understanding of the anatomic and physiologic principles and their anesthetic implications will lead to improved management of these extremely ill infants. We reported the anesthetic considerations and management of a case of tetralogy of Fallot with absent pulmonary valve of an infant who experienced severe respiratory distress on the supine position.

Anesthesia↗
PubMed1993

The D domain of the thyroid hormone receptor alpha 1 specifies positive and negative transcriptional regulation functions.

Four structural domains are characteristic of the members of the thyroid/steroid receptor superfamily. Of these, the A/B and D domains are the least conserved. We have investigated the role of two clusters of positively charged amino acids within the D domain of the thyroid hormone receptor alpha 1 (TR alpha 1). The sequences Lys134-Arg-Lys and Arg188-Arg-Lys, individually or together, were substituted to the neutral residues TIT in three mutants named alpha 1-1, alpha 1-2, and alpha 1-3, respectively. Subcellular localization of transiently transfected wild-type and mutated TRs was monitored by immunostaining, using a TR alpha 1-specific antibody. The wild-type and the alpha 1-2 TRs were detected exclusively in the nucleus, in the presence or absence of thyroid hormone. In contrast, the alpha 1-1 and alpha 1-3 mutants accumulated in both cytoplasm and nucleus, underscoring the importance of the Lys134-Arg-Lys residues for correct nuclear targeting. More importantly, although the mutants had unimpaired DNA- and hormone-binding activities, all three had lost positive and negative transcriptional regulatory functions. Thus, transactivation and repression functions can be entirely dissociated from the other properties of the receptor. In addition, substitution of either one of the positively charged amino acid clusters was sufficient to convert the native TR alpha 1 into a dominant, thyroid hormone-dependent receptor antagonist. These observations, which underline the functional relevance of the D domain for TR alpha 1 function, may also have implications for the autosomal dominant syndrome of generalized resistance to thyroid hormone.

Amino Acid Sequence↗
PubMed1993

Characterization of the functional domain of tissue inhibitor of metalloproteinases-2 (TIMP-2).

Analysis of the functional domain of tissue inhibitor of metallo-proteinases-2 (TIMP-2) was performed using limited proteolytic degradation with trypsin. This treatment generated a 13.5 kDa fragment which was purified and shown to consist of an uncleaved N-terminal region extending from residue 1 to residue 132. The fragment retains the ability to inhibit activated interstitial collagenase and to block the autocatalytic activation of procollagenase.

Amino Acid Sequence↗