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Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 145 records · Page 8Linked to original sources

Effect of 6-OHDA injection on the AMPA glutamate receptor subunits in the substantia nigra of Sprague-Dawley rats.

Parkinson's disease (PD) is characterized by the destruction of dopaminergic cells in the substantia nigra (SN). The cause of the cell death and the development of Parkinsonism is however unknown. There are increasing evidences to suggest the involvement of glutamate mediated by its receptors. Using immunohistochemistry and cell counting, the present study investigated whether the numbers of neurons immunostained with glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR1, GluR2/3 and GluR4 in the SN of rats would change after the injection of 6-hydroxydopamine (6-OHDA) into the SN. The results showed that the numbers of GluR1 positive cells were significantly decreased in the substantia nigra pars compacta (SNc), pars reticulata (SNr) and pars lateralis (SNl) from 3 days (13.7%) to 3 months (40.3%) and of GluR2/3 cells, from 1 week (17.6%) to 3 months (19.1%) after 6-OHDA injection, compared to those in the contralateral non-injected side. There was, however, no significant difference in the number of GluR4 positive cells between the injected and non-injected SN. The results were discussed.

Animals↗

Enteric absorption of FK 506: estimation by a block liver perfusion technique in rats.

This perfusion model enables a pharmacokinetic study of enteral absorption and hepatic metabolic rate simultaneously. FK 506 is absorbed mainly via the proximal small intestine and metabolized rapidly by the liver during single passage. These results may lead to further analyses of absorption and metabolism of FK 506 under various conditions.

Animals↗

Characterization of neocortical non-pyramidal neurons expressing preprotachykinins A and B: a double immunofluorescence study in the rat.

Neurons expressing preprotachykinin A and preprotachykinin B, which are the precursor prepropeptides of substance P and neurokinin B (neuromedin K), respectively, were characterized immunocytochemically in the rat neocortex. Antibodies raised against C-terminal portions of preprotachykinins were used for labeling cell bodies of preprotachykinin-producing neurons. Neurons immunoreactive for preprotachykinin B were encountered four times more frequently in the neocortex than those immunoreactive for preprotachykinin A. Preprotachykinin A-immunoreactive neurons were scattered more frequently in the deep cortical layers (layers IV-VI) than in the superficial layers (layers I-III), whereas preprotachykinin B-immunoreactive neurons were distributed more frequently in the superficial layers than in the deep layers. Almost all preprotachykinin-expressing neurons were immunoreactive for GABA, suggesting that they were non-pyramidal cells. However, co-expression of the two preprotachykinin immunoreactivities in single neurons was not found. Preprotachykinin-expressing neocortical neurons were further examined with markers for subpopulations of GABAergic cortical neurons. Immunoreactivities for parvalbumin, calbindin and somatostatin were found in 69%, 27% and 11%, respectively, of preprotachykinin A-immunoreactive neurons. Conversely, preprotachykinin A-immunoreactive neurons constituted only 6% of parvalbumin-immunoreactive neurons, 4% of calbindin-immunoreactive neurons and 1% of somatostatin-immunoreactive neurons. Immunoreactivities for calretinin, choline acetyltransferase, vasoactive intestinal polypeptide, corticotropin-releasing factor and cholecystokinin were detected in 13-39% of preprotachykinin B-immunoreactive neurons. Preprotachykinin B immunoreactivity was seen in 33% of calretinin-positive neurons, 45% of cholinergic neurons, 47% of vasoactive intestinal polypeptide-positive neurons, 59% of corticotropin-releasing factor-positive neurons and 83% of cholecystokinin-positive neurons. These results indicate that preprotachykinin A- and preprotachykinin B-expressing neurons constitute separate populations of GABAergic non-pyramidal neurons in the neocortex. Since receptors for substance P and neurokinin B are expressed in GABAergic neurons [Kaneko T. et al. (1994) Neuroscience 60, 199-211] and pyramidal neurons [Ding Y. Q. et al. (1996) J. comp. Neurol. 364, 290-310], respectively, cortical neurons may use two separate lines of tachykinin signals; substance P serves as a signal between GABAergic non-pyramidal neurons, whereas neurokinin B acts as a signal of GABAergic neurons to pyramidal neurons.

Amino Acid Sequence↗

Detection and preliminary characterization of matrix metalloproteinase activity in temporomandibular joint lavage fluid.

In this study, lavage fluid was fractionated from the superior joint space in patients with temporomandibular joint (TMJ) dysfunction. A hide powder azure protease assay was used to assess protease activity in lavage fluid. No correlation between a patient's pain and the level of protease activity was demonstrated. Latent as well as active proteases were detected in the sample lavage fluid. Latent matrix metalloproteinases (MMPs) were activated using trypsin. Stromelysin-1 was detected in an active form in lavage fluid by immunozymography. The presence of high molecular weight species with protease activity was also demonstrated. This study validates the presence of stromelysin-1 as well as other MMPs in TMJ lavage fluid and proposes a mechanism for their physiologic activation.

Collagen↗

Endogenous ouabain secretion in man is not regulated by ACTH.

It has been suggested that endogenous ouabain-like substance (OLS) is of adrenal origin and the secretion of OLS may be ACTH dependent. To determine if OLS is influenced by the pituitary-adrenal axis, we studied the effect of adrenal stimulation (0.25 mg Synacthen) and suppression (1 mg Dexamethasone) on two separate groups of nine subjects. Serum OLS was measured by a radioimmunoassay (RIA) developed in our lab, and cortisol and ACTH were measured by commercial assay kits. Dexamethasone significantly (P< 0.001) suppressed serum cortisol and ACTH concentrations, without effecting endogenous OLS concentration (0.64+/-0.17 vs 0.85+/-0.18nmol/l). Synacthen increased the concentration of cortisol in serum (p < 0.001) over the test period; OLS concentration, again, remained unchanged (0.45+/-0.04 vs 0.43+/-0.05 nmol/l). In further studies, serum concentrations of cortisol and OLS were compared between left (LAV) and right (RAV) adrenal veins with that from the inferior vena cava (IVC). Concentration of cortisol in the LAV and RAV was five-fold greater than that in IVC. However, there was no difference in OLS concentration at the corresponding sites. In addition, serum OLS concentrations in patients having undergone bilateral adrenalectomy or diagnosed with Addison's disease (0.62+/-0.19 nmol/l) were similar to concentrations in healthy subjects (0.67+/-0.21 nmol/l). Examination of bovine adrenal, liver, kidney, heart and human placenta demonstrated that OLS content of bovine adrenal was comparable with other tissues analysed. HPLC studies of human serum and bovine adrenal gland produced identical elution profiles, resolving a single peak which coincided with the retention time observed for standard ouabain. We conclude that the adrenal is unlikely to be the source of endogenous OLS, the secretion of which appears to be independent of ACTH.

Addison Disease↗

Medial smooth muscle cell loss in arterial allografts occurs by cytolytic cell induced apoptosis.

OBJECTIVE: Experimental arterial allografts, used as models of chronic rejection, undergo marked loss of smooth muscle cells (SMC) from their media prior to the development of occlusive, intimal proliferative lesions. Medial SMC loss has been described in human heart transplants, and may be related to the development of occlusive coronary lesions which are the hallmark of chronic rejection. This SMC loss does not exhibit the characteristics of necrotic cell death. We sought to determine whether medial SMC loss in arterial allografts occurs by apoptosis. We further investigated these allografts for cytolytic cell-derived inducers of apoptosis, Finally, we compared two different strain combinations to assess the impact of varying histoincompatability on medial SMC loss. METHODS: Evidence for internucleosomal DNA degradation, which is characteristic of apoptosis, was sought by the in situ terminal deoxynucleotidyl transferase nick end labelling (TUNEL) method carried out on Lewis to Fisher rat femoral artery transplants (disparate at minor loci only) and Brown Norway to Lewis aortic transplants (fully disparate at major and minor loci). Isografts (Lewis to Lewis) served as controls. In a separate series of experiments graft mRNA was extracted and analysed by reverse transcription-polymerase chain reaction (RT-PCR) with primers for molecular inducers of apoptosis (TNF-alpha, Fas ligand, perforin, and granzyme-B) which are derived from cytolytic cells known to be present in allografts. RESULTS: Allograft media contained large numbers of TUNEL stained nuclei in both strain combinations. Neither isografts nor ungrafted femoral artery segments stained positive for apoptosis. RT-PCR on whole allografts in both strain combinations revealed sustained upregulation of perforin, granzyme-B, Fas-ligand and TNF-alpha mRNA concomitant with medial SMC loss. Autografts demonstrated sustained up regulation of TNF-alpha, and perforin, but only brief upregulation of granzyme-B, and no upregulation of Fas-ligand. CONCLUSIONS: These data strongly suggest that medial SMC loss in allograft arteriopathy occurs by apoptosis. Further, RT-PCR data indicate that cytolytic cell-derived inducers of apoptosis are upregulated in these grafts and may be accountable for medial SMC apoptotic cell death. Finally, fully-disparate (Brown Norway to Lewis) and minor-only incompatible (Lewis to Fisher) strain combinations both resulted in marked intimal proliferation, medial SMC loss by apoptosis, and similar patterns of expression of cytolytic cell derived inducers of apoptosis. Insofar as intimal proliferative lesion-formation may be dependent on medial damage (as in arterial-injury models), understanding the mechanism of medial SMC loss may provide a novel therapeutic approach to human cardiac transplant arteriopathy.

Animals↗

Laparoscopic removal of a bladder leiomyoma.

Bladder leiomyoma is a rare tumor that is generally removed by transabdominal, vaginal, and transurethral approaches. We successfully removed a large, transmural, extravesical bladder leiomyoma by laparoscopy.

Adult↗

The Pumilio RNA-binding domain is also a translational regulator.

Posterior patterning in the Drosophila embryo requires the action of Nanos (Nos) and Pumilio (Pum), which collaborate to regulate the translation of maternal hunchback (hb) mRNA. Previous work demonstrated that Pum recognizes sites in the 3' UTR of hb mRNA. In this report, we first define the RNA-binding domain of Pum and then show that residues essential for translational repression are embedded within this domain. We also show that Nos and Pum can repress cap-independent translation from an internal ribosome entry site (IRES) in vivo, suggesting that they act downstream of the initial steps of normal, cap-dependent translation.

Amino Acid Sequence↗

Race and gender as components of the working self-concept.

A sample of 78 U.S. students carried beepers for 1 week and reported in situ on their awareness of gender and race. The participants to whom gender and race were more important were more aware of those characteristics, and their awareness of gender and race was more variable across situations. Awareness was higher in public than in private settings; it was also higher during athletic than during academic involvement. The White participants were more aware of race when they were in the racial minority; the non-White participants were more aware of race when they were in the racial majority. All the participants were more aware of gender when they were in the gender minority.

Adolescent↗

Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers.

OBJECTIVE: To evaluate the effect of administration of 1 ampule of 50% dextrose in water solution (D50W) on serum glucose levels in healthy adult volunteers, the authors set out to determine whether a pre-D50W serum glucose level can be predicted from the ED sample. METHODS: This was a prospective, interventional study conducted from the ED of an urban, university-affiliated hospital. All subjects were healthy employee volunteers between 25 and 40 years of age. Baseline serum glucose levels were determined and all subjects were given an i.v. bolus of 25 grams of 50% dextrose solution. The main outcome measures were post-D50W serum glucose levels (observed) at 5 predetermined time intervals (5 min, 15 min, 30 min, 1 hr, and 2 hr). An expected change in serum glucose was calculated using the volume of distribution formula for glucose. RESULTS: Twenty-five volunteers (17 males and 8 females) participated in the study. The mean baseline serum glucose was 82.3 +/- 13.5 mg/dL. The mean post-infusion levels were: 244.4 +/- 44.6 mg/dL (5 min), 145.8 +/- 52.3 mg/dL (15 min), 88.1 +/- 28.8 mg/dL (30 min), 77.6 +/- 13.6 mg/dL (60 min), and 83.2 +/- 11.4 mg/dL (120 min). Using a mixed-effect regression model, statistically significant increases in serum glucose levels were found at 5 minutes (p < 0.001) and 15 minutes (p < 00001) following administration of D50W. There was a return to baseline serum glucose by 30 minutes. The expected change based on the volume of distribution formula (53.7 +/- 34.9) did not correlate with the observed changes at any measured time interval. CONCLUSION: Without pre-intervention blood drawing by emergency medical services, it is not possible to accurately predict pre-D50W serum glucose levels based on post-D50W glucose levels. The diagnosis of hypoglycemia as the etiology of altered mental status must therefore remain a diagnosis of exclusion. In addition, the return of serum glucose to baseline after 30 minutes suggests the duration of the effect of 1 ampule of D50W. Frequent re-evaluation of the serum glucose levels of suspected or proven hypoglycemic patients after administration of D50W should be considered.

Adult↗

Assessing incidence rates and secular trends in nonmelanocytic skin cancer: which method is best?

BACKGROUND: Evaluating the incidence of nonmelanocytic skin cancers in white populations and assessing the direction and strength of secular trends in these cancers have become important issues to dermatologists, oncologists, health policy analysts, and health care funders. OBJECTIVE: The objective of this paper is to evaluate the three principal methods used to assess incidence rates and secular trends. CONCLUSIONS: Each of the three methods has strengths and weaknesses. An understanding of these will enable proper assessment of the value and significance of findings presented in the literature.

Epidemiologic Methods↗

Production and characterization of fusion proteins containing transferrin and nerve growth factor.

To explore the ability to use genetic fusions of transferrin as a carrier for brain targeting and delivery, a series of fusion proteins containing both human nerve growth factor (NGF) and human transferrin was produced in mammalian cells. A protein in which the hinge region from human IgG3 joined the carboxyl terminus of NGF and the amino terminus of transferrin formed a covalent homodimer, bound human transferrin receptor, and retained full NGF in PC12 cells. In contrast, proteins in which polypeptide dimerization was not induced or in which NGF was fused through its amino terminus had greatly reduced NGF activity. The ability to maintain both biologically active NGF and transferrin as part of a fusion protein may offer a novel way to deliver NGF and other neurotrophic factors to the central nervous system.

Blood-Brain Barrier↗

Safety and clinical efficacy of zileuton in patients with chronic asthma.

Zileuton, a leukotriene pathway inhibitor used to treat asthma, improves lung function, relieves symptoms, and is well tolerated. The purpose of this 12-month, parallel-group, open-label study was to assess the efficacy of zileuton and evaluate liver function in patients treated with this drug (approximately 2% of patients treated with zileuton in controlled trials had reversible liver enzyme elevations). A total of 2,947 patients at 233 centers in the United States were randomly assigned in a 5:1 ratio to treatment with zileuton plus usual asthma care or usual asthma care alone. Efficacy variables included asthma exacerbations; need for alternative treatment, steroid rescue, emergency care, and hospitalizations; forced expiratory volume in 1 second (FEV1); and asthma symptom scores. The safety evaluation included measurement of alanine aminotransferase levels. Patients treated with zileuton had significantly fewer corticosteroid rescues (P < 0.001), required less emergency care (P < 0.05), had fewer hospitalizations, and had greater increases in FEV1 (P = 0.048). They also had significantly greater improvements in asthma symptoms. Increases in alanine aminotransferase levels to three times or more the upper limit of normal occurred in 4.6% of patients treated with zileuton and 1.1% of those receiving usual care (P < 0.001); most increases occurred during the first 2 to 3 months. Alanine aminotransferase levels decreased to less than two times the upper limit of normal or to baseline levels during zileuton treatment or after drug cessation. Jaundice or chronic liver disease did not develop in any patient. Adding zileuton to the therapeutic regimens of patients with asthma is likely to improve asthma control and lower utilization of healthcare resources.

Asthma↗

[Aortic and mitral valve aneurysms complicated with infective endocarditis: a case report].

A rare case of aortic and mitral valve aneurysms complicated with infective endocarditis was accurately diagnosed by transesophageal echocardiography. A 57-year-old man with severe aortic regurgitation due to infective endocarditis was admitted to our hospital. Transthoracic echocardiography showed an aortic valve aneurysm on the right coronary cusp and perforations on the other cusps. Transesophageal echocardiography demonstrated a small aneurysm on the anterior leaflet of the mitral valve which was not clearly visualized by transthoracic echocardiography. Color Doppler echocardiography revealed severe aortic regurgitation and mild mitral regurgitation without perforation of the mitral valve aneurysm. Aortic valve replacement and mitral valvuloplasty of the anterior mitral leaflet were performed. The right coronary cusp of the aortic valve showed marked thinning with infiltration of inflammatory cells. The postoperative clinical course was uneventful.

Aortic Valve↗

Delayed postpartum uterine dehiscence. A case report.

BACKGROUND: Delayed postpartum uterine dehiscence with hemorrhagic shock may be caused by inadequate treatment of postpartum endomyometritis. CASE: A woman developed a delayed uterine dehiscence six weeks postpartum. Inadequate antibiotic treatment for postpartum endomyometritis was thought to be the etiology. The patient required a hysterectomy for definitive treatment because of associated hemorrhagic shock. CONCLUSION: Only one other case of uterine dehiscence that resulted from endomyometritis has been reported. Broad-spectrum antibiotic therapy is indicated in postpartum endomyometritis to avoid uterine dehiscence with hemorrhagic shock.

Adult↗

[Detection of coronary artery disease by adenosine triphosphate stress echocardiography: comparison with adenosine triphosphate stress thallium myocardial scintigraphy and coronary angiography].

The clinical feasibility and usefulness of adenosine triphosphate-2Na (ATP) stress echocardiography for the detection of coronary artery disease (CAD) were assessed. Two-dimensional echocardiography and thallium-201 single photon emission computed tomography (SPECT) during ATP infusion were performed simultaneously in 58 consecutive patients (41 men and 17 women; mean age 66 +/- 12 years) with suspected CAD. ATP was infused intravenously at 0.16 mg/kg/min for 5 min and thallium was injected at 4 min. All patients underwent coronary angiography within 2 weeks of ATP echocardiography and ATP SPECT. An ischemic response during ATP infusion was detected by echocardiography as the development or worsening of a wall motion abnormality compared with the baseline and by SPECT as a perfusion defect that filled totally or partially during redistribution. Significant coronary artery stenosis was defined as > or = 75% diameter stenosis in a major epicardial vessel. The severity of the stenosis was classified as follows: Group A, lesions with significant coronary artery stenosis (> or = 75%, < 90%); Group B, lesions with severe coronary artery stenosis (> or = 90%) without collateral circulation; Group C, lesions with severe coronary artery stenosis (> or = 90%) with collateral circulation. Significant CAD was present in 43 of 58 patients. The overall sensitivity, specificity and accuracy of ATP echocardiography for detecting significant CAD were 70%, 100% and 78%, respectively, and those of ATP SPECT were 98%, 87% and 95%, respectively. In patients without previous myocardial infarction, the sensitivity of ATP echocardiography was 67%. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia were 59% and 95% in patients with 1-vessel disease, 75% and 100% in those with 2-vessel disease, and 88% and 100% in those with 3-vessel disease, respectively. The induction of wall motion abnormality by ATP echocardiography was highly concordant with ATP SPECT imaging in patients with multivessel disease. Although the sensitivity of ATP echocardiography improved in patients with multivessel disease more than in those with single-vessel disease, detection of all diseased vessels was achieved in only 10% of patients with multivessel disease. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia in individual vessels were: right coronary artery, 58% and 74%; left anterior descending artery, 59% and 97%; left circumflex artery, 27% and 68%. ATP-induced transient perfusion defects were associated with transient wall motion abnormality in only 57% of segments. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia in patients with severe coronary stenosis were: Group A, 32% and 66%; Group B, 60% and 93%; Group C, 80% and 95%. The sensitivity of ATP echocardiography was significantly higher in the lesions with collateral circulation than in those without collateral circulation. ATP stress echocardiography is useful for detecting myocardial ischemia in patients with multivessel disease and in patients with severe coronary artery stenosis (> or = 90%). In particular, transient wall motion abnormality tends to be detected in the segments perfused by collateral circulation.

Adenosine Triphosphate↗