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Biomedical subjects

T T Lee

Publications and source records attributed to T T Lee.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials.

OBJECTIVES: We sought to evaluate the current evidence for an effect of beta-blockade treatment on mortality in patients with congestive heart failure (CHF). BACKGROUND: Although numerous small studies have suggested a benefit with beta-blocker therapy in patients with heart failure, a clear survival benefit has not been demonstrated. A recent combined analysis of several studies with the alpha- and beta-adrenergic blocking agent carvedilol demonstrated a significant survival advantage; however, the total number of events was small. Furthermore, it is unclear if previous studies with other beta-blockers are consistent with this finding. METHODS: Randomized clinical trials of beta-blockade treatment in patients with CHF from January 1975 through February 1997 were identified using a MEDLINE search and a review of reports from scientific meetings. Studies were included if mortality was reported during 3 or more months of follow-up. RESULTS: We identified 35 reports, 17 of which met the inclusion criteria. These studies included 3,039 patients with follow-up ranging from 3 months to 2 years. Beta-blockade was associated with a trend toward mortality reduction in 13 studies. When all 17 reports were combined, beta-blockade significantly reduced all-cause mortality (random effect odds ratio [OR] 0.69, 95% confidence interval [CI] 0.54 to 0.88). A trend toward greater treatment effect was noted for nonsudden cardiac death (OR 0.58, 95% CI 0.40 to 0.83) compared with sudden cardiac death (OR 0.84, 95% CI 0.59 to 1.2). Similar reductions in mortality were observed for patients with ischemic (OR 0.69, 95% CI 0.49 to 0.98) and nonischemic cardiomyopathy (OR 0.69, 95% CI 0.47 to 0.99). The survival benefit was greater for trials of the drug carvedilol (OR 0.54, 95% CI 0.36 to 0.81) than for noncarvedilol drugs (OR 0.82, 95% CI 0.60 to 1.12); however, the difference did not reach statistical significance (p = 0.10). CONCLUSIONS: Pooled evidence suggests that beta-blockade reduces all-cause mortality in patients with CHF. Additional trials are required to determine whether carvedilol differs in its effect from other agents.

Adrenergic beta-Antagonists↗
PubMed1997

Modified open-door cervical expansive laminoplasty for spondylotic myelopathy: operative technique, outcome, and predictors for gait improvement.

Twenty-five patients underwent an expansive cervical laminoplasty for nontraumatic cervical spondylosis with myelopathy during the period from June 1990 to November 1994, and all had a minimum of 18 months of follow-up review. The open-door laminoplasty procedure presently reported consisted of the same approach evaluated by Hirabayashi in 1977, except that the authors of this report used three rib allografts to anchor the "open door," rather than spinous process sutures or autologous bone grafts. Posterior foraminotomies and decompression were performed in patients with clinical radiculopathy and radiographic evidence of foraminal stenosis. Preoperatively, gait disturbance was present in all patients. All 25 patients (100%) had long-tract signs on presentation. Nondermatomal upper-extremity symptoms (numbness, tingling, weakness, and pain) were quite common in this group of patients. Bowel, bladder, and/or sexual dysfunction was found in 13 (52%) of 25 patients. Preoperative radiographic studies showed a mean midline anteroposterior diameter spinal canal/vertebral body (SC/VB) ratio of 0.623 and a mean compression ratio (sagittal/lateral diameter ratio x 100%) of 37%. This procedure was quite successful in relieving preoperative symptoms and few complications occurred. Gait disturbance was improved in 21 (84%) of 25 patients and hand numbness and tingling were improved in 13 (87%) of 15 patients. Bowel or bladder function improved in 10 (77%) of 13 patients. Radiculopathy, when present, was alleviated in all four patients after the decompressive procedure. The postoperative SC/VB ratio, as measured by plain lateral radiographs and/or computerized tomography scans, was improved to 0.871, a 38% improvement. In a comparison with the preoperative SC/VB ratio using the two-tailed t-test, alpha was less than 0.001. The compression ratio improved to 63% postoperatively, which yielded an alpha of less than 0.005 according to the two-tailed t-test. Only one postoperative complication, an anterior scalene syndrome, was encountered. Various predictors of surgical outcome based on gait improvement were evaluated. Age greater than 60 years at the time of presentation, duration of symptoms more than 18 months prior to surgery, preoperative bowel or bladder dysfunction, and lower-extremity dysfunction were found to be associated with poorer surgical outcome. Even when these conditions were present, gait improvement was noted in at least 70% of the patients.

Cervical Vertebrae↗
PubMed1997

Progressive posttraumatic myelomalacic myelopathy: treatment with untethering and expansive duraplasty.

Patients with progressive posttraumatic myelomalacic myelopathy (PPMM), or tethered cord syndrome, present with symptoms and signs similar to those observed in case of progressive posttraumatic cystic myelopathy, that is, sensorimotor function deterioration, local and/or radicular pain, increased spasticity, increased autonomic dysreflexia, and sphincter dysfunction. The authors investigated surgical outcomes of untethering combined with expansive duraplasty. Forty patients with PPMM who presented with functional deterioration underwent untethering of the spinal cord and nerve roots with an expansive duraplasty. Meticulous dissections of adhesions on the dorsal and lateral aspects of the spinal cord and nerve roots were performed. Intraoperative ultrasonography was used to detect the presence of a confluent cyst and to assess the success of untethering. After surgery, the patients were treated using a protocol that involved frequent turning for 48 hours and subsequently mobilization. Preoperative magnetic resonance (MR) imaging, with and without administration of a contrast agent, was obtained in all patients, except one patient who underwent immediate and delayed computerized tomography (CT) myelography. The mean follow-up period was 3 years (range 20-57 months) for the 36 patients available for follow-up review. Spinal cord tethering was observed in all patients preoperatively. Trauma was the most common cause of this pathology, accounting for 31 of the 40 cases. Preoperative MR imaging did not demonstrate tumor recurrence in the group of five patients who had undergone an initial operation for tumor excision. The interval between the causative event and the operation was less than 5 years in half of the patients (20 of 40), with the longest interval lasting up to 37 years. Motor function deterioration was the most frequent manifestation; it was present in 31 of 40 patients. Improvements in motor function, autonomic dysreflexia, pain, sphincter dysfunction, and sensory function were found during the most recent follow-up examination in 79%, 75%, 62%, 50%, and 43% of the patients, respectively. Two patients experienced retethering of the spinal cord and one underwent a second operation. Surgical untethering and expansive duraplasty, followed by postoperative position rotation to avoid retethering, provide symptomatic relief for patients with PPMM.

Adolescent↗
PubMed1996

Overexpression of protein kinase FA/GSK-3 alpha (a proline-directed protein kinase) correlates with human hepatoma dedifferentiation/progression.

Computer analysis of protein phosphorylation sites sequence revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3 alpha (kinase F(A)/GSK-3 alpha) (a member of PDPK family) has been optimized for human hepatoma and used to demonstrate for the first time significantly increased (P < 0.01) activity in poorly differentiated SK-Hep-1 hepatoma (24.2 +/- 2.8 units/mg) and moderately differentiated Mahlavu hepatoma (14.5 +/- 2.2 units/mg) when compared to well differentiated Hep 3B hepatoma (8.0 +/- 2.4 units/mg). Immunoblotting analysis revealed that increased activity of kinase FA/GSK-3 alpha is due to overexpression of the protein. Elevated kinase FA/GSK-3 alpha expression in human hepatoma biopsies relative to normal liver tissue was found to be even more profound. This kinase appeared to be fivefold overexpressed in well differentiated hepatoma and 13-fold overexpressed in poorly differentiated hepatoma when compared to normal liver tissue. Taken together, the results provide initial evidence that overexpression of kinase FA/GSK-3 alpha is involved in human hepatoma dedifferentiation/progression. Since kinase FA/GSK-3 alpha is a PDPK, the results further support a potential role of this kinase in human liver tumorigenesis, especially in its dedifferentiation/progression.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1996

Arteriovenous malformation associated with pleomorphic xanthoastrocytoma.

A case of a left temporo-occipital arteriovenous malformation associated with a pleomorphic xanthoastrocytoma is described. The patient had the vascular lesion with a stable right hemiparesis for many years prior to his recent clinical deterioration. Correlation is made with nine previously reported cases of angiogliomas. With the close proximity and temporal correlation of the two components of this lesion, as well as pathological evidence, the authors propose that angioglioma may be the product of reactive glial proliferation and transformation secondary to a pre-existing vascular malformation and hemorrhage.

Astrocytes↗
PubMed1996

Hyperglycemia induced activation of type-1 protein phosphatase activator (kinase FA) in perfused human placenta.

We report the identification of type-1 protein phosphatase activating factor (kinase FA), a unique biologic mediator for both insulin and epidermal growth factors in the human placenta. The activity of kinase F, was found to be extremely labile in the unperfused placenta. Fresh term placentas lost more than 50% of the total kinase FA activity within 6 hours when exposed to air of incubated in medium but not perfused. In contrast, the activity of kinase FA was stable when the human term placenta was dually perfused. This indicates that placental dual perfusion is a useful method for studying protein phosphorylation-dephosphorylation involved in signal transduction. When fresh placentas were perfused with media containing glucose at 141 +/- 10, 242 +/- 12 and 436 +/- 20 mg/dL, kinase FA activity was stimulated several-fold in a glucose concentration-dependent manner when compared with control levels at delivery. The results suggest that hyperglycemia-mediated activation may represent a previously unknown control mechanisms for the regulation of protein kinase FA. The results also suggest that human placental perfusion is a good in vitro system for studying signal transduction mechanisms involved in hormonal actions and metabolic regulation.

Analysis of Variance↗
PubMed1995

Overexpression of cellular activity and protein level of protein kinase FA/GSK-3 alpha correlates with human thyroid tumor cell dedifferentiation.

Computer analysis of protein phosphorylation sites sequence revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (a member of the PDPK family) has been optimized for human thyroid tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in thyroid carcinoma (24.2 +/- 2.8 units/mg of protein) (n = 7), thyroid adenoma (14.5 +/- 2.2 units/mg of protein) (n = 6), and thyroid hyperplasia (8.0 +/- 2.4 units/mg of protein) (n = 5) when compared to five normal controls (4.1 +/- 1.8 units/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3 alpha in thyroid tumor cells is due to overexpression of the protein synthesis of the enzyme. Taken together, the results provide initial evidence that overexpression of protein level and cellular activity of kinase FA/GSK-3 alpha is involved in human thyroid tumor cell dedifferentiation, supporting an association of PDPK with neoplastic transformation and tumorigenesis. Since kinase FA/GSK-3 alpha may function as a possible regulator of transcription factors/protooncogenes, kinase FA/GSK-3 alpha may therefore play an important role in thyroid cell carcinogenesis, especially in its differentiation.

Adenoma↗
PubMed1995

Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder.

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3 alpha activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.

Amino Acid Sequence↗
PubMed1995

Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

Amino Acid Sequence↗
PubMed1995

Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.

OBJECTIVE: To study the effect of E2 and P on the epithelial cell cycle of normal human breast in vivo. DESIGN: Double-blind, randomized study. Topical application to the breast of a gel containing either a placebo, E2, P, or a combination of E2 and P, daily, during the 10 to 13 days preceding breast surgery. PATIENTS: Forty premenopausal women undergoing breast surgery for the removal of a lump. MAIN OUTCOME MEASURES. Plasma and breast tissue concentrations of E2 and P. Epithelial cell cycle evaluated in normal breast tissue areas by counting mitoses and proliferating cell nuclear antigen immunostaining quantitative analyses. RESULTS: Increased E2 concentration increases the number of cycling epithelial cells. Increased P concentration significantly decreases the number of cycling epithelial cells. CONCLUSION: Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.

Administration, Topical↗
PubMed1994

Spontaneous injection in microcolumn separations.

The phenomenon of spontaneous (ubiquitous) injection in microcolumn separations has been characterized to improve quantitative precision for ultramicrosampling and to enhance separation efficiency. By combining fluorescence imaging, video microscopy, and measurements from capillary electrophoresis, we demonstrate that spontaneous injection is caused primarily by an interfacial pressure difference formed at the inlet of the capillary. This complex injection mechanism has been modeled with some simple assumptions based on fluid dynamics. In particular, studies showed that extraneous injection is reduced up to 12-fold by etching the capillary inlet or by using a thin-walled capillary. Variations by a factor of 2 in the injection length can result from delays between sample introduction and reinsertion into the inlet vial if the timing is not controlled precisely. Evidence is presented that evaporation of buffer from the inlet can reduce the injection length by more than 1 order of magnitude.

Image Processing, Computer-Assisted↗
PubMed1994

Autophosphorylation-dependent protein kinase phosphorylates Ser25, Ser38, Ser65, Ser71, and Ser411 in vimentin and thereby inhibits cytoskeletal intermediate filament assembly.

The autophosphorylation-dependent protein kinase has been identified as a potent vimentin kinase that incorporates 2 mol of phosphates per mol of protein and generates five major phosphorylation sites in vimentin. Tryptic phosphopeptide mapping by high-performance liquid chromatography followed by sequential manual Edman degradation and direct peptide sequence analysis revealed that Ser-25, Ser-38, Ser-65, and Ser-71 in the amino-terminal domain and Ser-411 in the carboxyl-terminal domain are the phosphorylation sites in vimentin phosphorylated by this kinase, indicating that autophosphorylation-dependent protein kinase is a potent and unique vimentin kinase. Functional study further revealed that phosphorylation of vimentin by autophosphorylation-dependent protein kinase can completely inhibit polymerization and assembly of the cytoskeletal intermediate filament as demonstrated by electron microscopic analysis. Taken together, the results provide initial evidence that the autophosphorylation-dependent protein kinase may function as a vimentin kinase involved in the structure-function regulation of the cytoskeletal system. The results also support the notion that this cyclic nucleotide- and calcium-independent protein kinase may function as a multisubstrate/multifunctional protein kinase involved in the regulation of diverse cell functions.

Amino Acid Sequence↗
PubMed1994

Assessment of four rapid urease test systems for detection of Helicobacter pylori in gastric biopsy specimens.

An in vitro experiment and an in vivo clinical trial were both performed in order to assess the efficacy of four biopsy urease test systems, including one commercial kit, Temmler CUT test (Temmler Pharma, Marburg, Germany), for the rapid detection of Helicobacter pylori. We first evaluated four rapid urease test systems by inoculating bacterial suspensions of different concentrations into urea-containing media and observing the color change at room temperature. We found that the CUT test was superior in vitro to the other three urease test systems. As was expected, the lower the concentration of the inoculum, the slower was the color change and the fewer were the positive results noted. The minimal concentration of H. pylori for a positive urease test at 24 h was 1000-10,000 colony-forming units/ml in 1 drop of bacterial suspension inoculated. We then evaluated four biopsy urease test systems for the rapid diagnosis of H. pylori infection in antral and fundal mucosa biopsy specimens of 37 patients undergoing upper gastrointestinal endoscopy. All four test systems were 100% specific when compared with culture. In 69 culture-positive biopsy specimens, the CUT test was not only more sensitive (72%) than the other three systems (42%, 51%, and 45%, respectively), but also gave the fastest reaction by detecting more culture-positive biopsy specimens after 3 h of incubation at room temperature. The differences were statistically significant.

Bacteriological Techniques↗
PubMed1994

Antitumor agents--CLI. Bis(helenalinyl)glutarate and bis(isoalantodiol-B)glutarate, potent inhibitors of human DNA topoisomerase II.

Evaluation of a number of cytotoxic antitumor sesquiterpene lactones and their derivatives has led to the discovery of bis(helenalinyl)glutarate (4) and bis(isoalantodiol-B)glutarate (10) as potent inhibitors of human-derived topoisomerase II. Unlike etoposide, which inhibits by preventing the DNA rejoining process, compounds 4 and 10 inhibit topoisomerase II without causing DNA breakage. The structure-activity relationships of 4, 10, and related compounds are discussed.

Cell Line↗
PubMed1994

Suksdorfin: an anti-HIV principle from Lomatium suksdorfii, its structure-activity correlation with related coumarins, and synergistic effects with anti-AIDS nucleosides.

Suksdorfin (1), which is isolated from the fruit of Lomatium suksdorfii, was found to be able to inhibit HIV-1 replication in the T cell line, H9, with an average EC50 value of 2.6 +/- 2.1 microM. In addition, suksdorfin was also suppressive during acute HIV-1 infections of peripheral blood mononuclear cells, monocyte/macrophages and the promonocytic cell line, U937. Combinations of 1 and the anti-HIV nucleosides ddI and ddC demonstrated statistical synergy in inhibiting HIV-1 replication (ddC > ddI). However, the viral inhibition mediated by combining 1 with AZT was not statistically synergistic. Furthermore, the presence of suksdorfin did not antagonize the suppression mediated by the three nucleoside reverse transcriptase inhibitors. Comparison of the structure and activity of 1 with those of ten related compounds indicated that the dihydroseselin type of pyranocoumarin possessing a 4'-isovaleryl group is important to suksdorfin's enhanced anti-HIV activity.

Antiviral Agents↗
PubMed1994

Subdural recording and electrical stimulation for cortical mapping and induction of usual seizures.

Chronic subdural strip electrodes were used for recording of seizure origin, cortical mapping and confirmation of seizure foci by electrical stimulation. Seventeen patients were comprehensively evaluated for epilepsy surgery. All patients had failed medical treatment. Intracranial recording was necessary in 12 patients. Speech area was determined in 50% of the patients stimulated. Seizure origin was confirmed by stimulation-induced usual seizures or aura in 75% of the patients stimulated. Intracranial chronic recordings were safe and added important prognostic information, as well as helped decide the extent of resection.

Adult↗
PubMed1993

Lymphokine induction of rat microglia multinucleated giant cell formation.

Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules.

Animals↗