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Biomedical subjects

K T Lin

Publications and source records attributed to K T Lin.

At least 19 recordsLinked to original sources
PubMed2006

Difficulty in securing treatment for degenerative hip disease in a patient with Down syndrome: the gap remains open.

In 2002, the office of the U.S. surgeon general published a report detailing the discrepancies between the quality of healthcare afforded to persons with and without mental retardation. This article examines the case of a female resident of a developmental center with profound mental retardation due to Down syndrome and degenerative hip disease. Although she was in urgent need of a total hip replacement, the operation was denied or delayed by several different surgeons. Using a survey of physician attitudes, we examine several possible motivations behind the surgeons' reluctance to perform the procedure and conclude that these reasons were not appropriate in this case. Finally, we reiterate the surgeon general's call to eradicate preconceptions held in the medical community about the population of persons with mental retardation that result in similar failures to provide adequate care.

Adult↗
PubMed2001

hTid-1, a human DnaJ protein, modulates the interferon signaling pathway.

The Jak family of protein-tyrosine kinases are crucial for the signaling of a large number of different polypeptide ligands, including the interferons, many cytokines, erythropoietin, and growth factors. Through their interaction with receptors, the Jaks initiate a signaling cascade resulting in the activation of gene transcription and ultimately a cellular response to various ligands. In addition to their role in cellular signaling, alteration of Jak activity has been implicated in several disease states. In identifying Jak2-interacting proteins with the yeast two-hybrid system, we cloned the human homologue of the Drosophila melanogaster tumor suppressor gene lethal () tumorous imaginal discs, which encodes the protein Tid56. Drosophila Tid56 and its human homologue hTid-1 represent members of the DnaJ family of molecular chaperones. The TID1 gene encodes two splice variants hTid-1(S) and hTid-1(L). We confirmed the interaction between Jak2 and hTid-1(S) or hTid-1(L) by immunoprecipitation from COS-1 cells expressing these proteins. The interaction between endogenous hTid-1 and Jak2 was shown in HEp2 cells. We further showed that hTid-1 interacts with the human interferon-gamma (Hu-IFN-gamma) receptor subunit IFN-gamma R2. In addition, using a chimeric construct where the extracellular domain of IFN-gamma R2 was fused to the kinase domain of Jak2, we showed that hTid-1 binds more efficiently to the chimera with an active kinase domain than to a similar construct with an inactive kinase domain. Additionally, the data demonstrate that hTid-1 isoforms as well as Jak2 interact with Hsp70/Hsc70 in vivo, and the interaction between Hsp70/Hsc70 and hTid-1 is reduced after IFN-gamma treatment. Furthermore, both hTid-1(S) and hTid-1(L) can modulate IFN-gamma-mediated transcriptional activity.

Animals↗
PubMed2001

Cloning and functional expression of the mucrosobin protein, a beta-fibrinogenase of Trimeresurus mucrosquamatus (Taiwan Habu).

A venom-specific cDNA encoding for a thrombin-like enzyme designated as mucrosobin has been cloned and sequenced from the cDNA library of the venomous gland of Trimeresurus mucrosquamatus. The full-length cDNA of mucrosobin was assembled by oligonucleotide screening and 5'-rapid amplification of cDNA ends. The amino acid sequence deduced from the cDNA consists of 257 amino acid residues with a putative signal peptide of 24 residues. It is highly homologous to the other thrombin-like enzymes (batroxobin, mucofirase, and calobin), suggesting that it is a serine proteinase with a conserved catalytic triad of His(41), Asp(84) and Ser(179) in the deduced form of mucrosobin protein. Northern blot analysis revealed that the mucrosobin gene encodes an mRNA of 1.5 kb and suggested a tissue-specific expression in the venomous gland. In an effort to study the biological property of mocrosobin, we have expressed the 28-kDa protein as inclusion bodies in Escherichia coli. For analyzing enzymatic activity, the inclusion bodies were solubilized and the recombinant protein was refolded with a two-step dialysis protocol. The refolded recombinant protein exhibited a specific beta-fibrinogenolytic activity. This study offers a possibility of using genetic engineering to acquire a functional snake venom protein with therapeutic potential.

Amino Acid Sequence↗
PubMed2001

Colon epithelial cell death in 2,4,6-trinitrobenzenesulfonic acid-induced colitis is associated with increased inducible nitric-oxide synthase expression and peroxynitrite production.

Peroxynitrite, derived from the reaction of nitric oxide (NO(.)) with superoxide (O(2)), is a potent nitrating and oxidizing agent that can induce apoptosis in a variety of different cell types. In the present study, we investigated the possible role of peroxynitrite as a mediator of colon epithelial cell death in rat colitis. Rat colon inflammation was induced by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and rats were sacrificed 24 h after TNBS administration. Expression of inducible nitric-oxide synthase (iNOS) was detected by reverse transcription-polymerase chain reaction and immunohistochemistry. The enzymatic activities of Ca(2+)-independent iNOS and Ca(2+)-dependent constitutive nitric-oxide synthase were determined biochemically. Evidence of peroxynitrite-mediated cell injury was detected by immunostaining of nitrotyrosine. Apoptosis was examined by in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and DNA gel electrophoresis. To evaluate the specific contribution of peroxynitrite to the observed cell injury, a selective iNOS inhibitor, L-N(G)-[1-iminoethyl]lysine (L-NIL), was administered after TNBS induction. Morphological examination and analysis of TUNEL/cytokeratin double immunofluorescence revealed significant apoptosis in mucosal epithelial cells. Nitrotyrosine was colocalized with TUNEL, strongly demonstrating the association of peroxynitrite with the apoptotic death of colon epithelial cells. The administration of L-NIL reduced iNOS activity in 24-h lesions by 92% and also significantly attenuated both nitrotyrosine staining and apoptotic cell counts in the colon epithelium. These results strongly suggest that local elevated level of peroxynitrite produced from increased iNOS expression and activity is a major contributor to colon epithelial apoptosis during colon inflammation.

Animals↗
PubMed1999

Long-term beta-blocker therapy improves autonomic nervous regulation in advanced congestive heart failure: a longitudinal heart rate variability study.

BACKGROUND: beta-Blocker therapy is believed to modulate the detrimental effect of overcompensating neurohormonal activation in chronic heart failure. However, clinical doubts remain, particularly the physiologic sympathovagal balance. METHODS: To respond to clinical concern about worsening autonomic nervous perturbation in beta-blocker therapy of advanced congestive heart failure, 15 consecutive patients were longitudinally studied to elucidate the evolution of cardiac function versus 24-hour heart rate variability (HRV) before and after 1, 3, and 6 to 9 months of atenolol-combined therapy. RESULTS: Two patients died prematurely within 1 month. All 13 surviving patients showed improvement in New York Heart Association functional class, with decrease in left ventricular end-systolic and end-diastolic dimensions and increase in fraction shortening and ejection fraction by echocardiography after at least 3 months of atenolol use. The retarded therapeutic effect was accompanied by a general rise of total, very low, low-, and high-frequency components (9.0 +/- 0.5, 8.8 +/- 0.5, 6.2 +/- 0.6, and 6.1 +/- 0.5 vs 10.9 +/- 0.3, 10.7 +/- 0.4, 8.6 +/- 0.3, and 7.8 +/- 0.3; all P <.02) of daily HRV. This implied recovery of parasympathetic and baroreceptor function. Return of sympathovagal interaction was further supported by the suppression of Cheyne-Stokes type HRV as detected by Wigner-Ville distribution. CONCLUSIONS: Long-term beta-blocker therapy for advanced congestive heart failure upwardly regulates the autonomic nervous interaction in synchrony with the evolution of cardiac function performance.

Adrenergic beta-Antagonists↗
PubMed1998

Peroxynitrite induces apoptosis of HL-60 cells by activation of a caspase-3 family protease.

Apoptosis is an active process critical for the homeostasis of organisms. Enzymes of the caspase family are responsible for executing this process. We have previously shown that peroxynitrite (ONOO-), a biological product generated from the interaction of nitric oxide and superoxide, induces apoptosis of HL-60 cells. The aim of this study was to elucidate the mechanisms involved in the execution process of peroxynitrite-induced apoptosis. Proteolytic cleavage of poly(ADP-ribose) polymerase, an indication of caspase-3 family protease activation and an early biochemical event accompanying apoptosis, was observed in a time-dependent manner during peroxynitrite-induced apoptosis of HL-60 cells. Activation of caspase-3 during peroxynitrite-induced apoptosis was substantiated by monitoring proteolysis of the caspase-3 proenzyme and by measuring caspase-3 activity with a fluorogenic substrate. Furthermore, pretreatment of HL-60 cells with N-acetyl-Asp-Glu-Val-Asp-aldehyde, a specific inhibitor of caspase-3, but not N-acetyl-Tyr-Val-Ala-Asp-aldehyde, a specific inhibitor of caspase-1, decreased peroxynitrite-induced apoptosis. These results suggest that the activation of a caspase-3 family protease is essential for initiating the execution process of peroxynitrite-induced apoptosis of HL-60 cells.

Apoptosis↗
PubMed1997

Reactive oxygen species participate in peroxynitrite-induced apoptosis in HL-60 cells.

Peroxynitrite (ONOO-) is a physiological product generated by the interaction of superoxide (O2.-) and nitric oxide (.NO). We have previously shown that peroxynitrite induces apoptosis in HL-60 cells. In the present study, we demonstrated that peroxynitrite generates reactive oxygen species (ROS) in HL-60 cells. Brief exposure of HL-60 cells to ONOO- induced elevation of lucigenin chemiluminescence, indicating generation of superoxide anion. Exogenous superoxide dismutase (SOD), a scavenger of O2.-, fully abolished the chemiluminescence response, further supporting this notion. Following O2.- generation, the accumulation of hydrogen peroxide (H2O2) was observed. The addition of SOD exacerbated but that of catalase attenuated peroxynitrite-induced DNA fragmentation, suggesting that this H2O2 production contributes to the apoptotic process. In addition, pre-treatment of HL-60 cells with N-acetyl-L-cysteine (15 mM), a ROS scavenger, fully scavenged peroxynitrite-elicited ROS generation and effectively inhibited (ONOO-)-induced apoptosis, further enforcing this hypothesis. In summary, our results suggest that (ONOO-)-stimulated ROS formation may serve as a mechanism for the propagation of peroxynitrite-mediated apoptotic cell death in an intact cell system.

Apoptosis↗
PubMed1996

Identification and characterization of a high-affinity leukotriene B4 receptor on guinea pig T lymphocytes and its regulation by lipoxin A4.

A single class of high affinity leukotriene B4 (LTB4) receptors has been identified on the surface of guinea pig peritoneal exudate T lymphocytes. The Kd of these receptors is 1.6 nM, with a Bmax of 25.2 fmol/10(7) cells (1500 sites/cell). Receptor binding activity can be blocked by specific LTB4 receptor antagonists, but not by a specific LTD4 receptor antagonist, lipoxins A4 or B4 (LXA4, LXB4) or K252a, a protein kinase C inhibitor. Pretreatment of T lymphocytes with phorbol myristyl acetate or LXA4, reduced LTB4 receptor density in a concentration-dependent manner, although similar concentrations of LXB4 had no effect. LTB4 receptor down-modulation by LXA4 was reversed by K252a. 4 alpha-Phorbol 12,13-didecanoate, an inactive structural analogue of phorbol myristyl acetate, did not activate protein kinase C or decrease LTB4 receptor density. These results suggest that LTB4 receptor density on T cells may by ultimately down-regulated by a protein kinase C-dependent mechanism and are consistent with a physiological role of LXA4 in the modulation of inflammatory process.

Animals↗
PubMed1996

Leukotriene B4 modulates in vivo expression of delayed-type hypersensitivity by a receptor-mediated mechanism: regulation by lipoxin A4.

Leukotriene B4 (LTB4) is a potent proinflammatory arachidonic acid metabolite whose actions are mediated by specific receptors. Recent characterization of a high-affinity LTB4 receptor on the surface of guinea pig CD4+ T lymphocytes prompted examination of a possible role of LTB4 in modulating in vivo expression of delayed-type hypersensitivity (DTH) to tuberculin (PPD). In the absence of PPD, intradermal injections of LTB4 or LTB4/LTD4 receptor antagonists did not elicit delayed-onset erythema at 24 h. When injected together with PPD, LTB4 (1 fmol to 1 pmol) caused a significant 25 to 30% decrease in DTH expression, whereas LTB4 receptor antagonists SC-41930, LY-223982, ONO-4057 (0.1-10 nmol), caused a highly significant (P < .01) 25 to 50% increase. The effect of SC-41930 on DTH expression was inhibited by a 10-fmol dose of LTB4. LTD4 receptor antagonist LY-171883 had no effect on DTH expression. Lipoxin A4 (LXA4) interferes with binding of LTB4 to T lymphocytes or neutrophils by reducing LTB4 receptor density. It caused a small but significant enhancement of DTH expression at 1-nmol doses when injected with PPD. Lipoxin B4 had no effect. Enhancement or inhibition of grossly visible delayed skin responses to PPD by LTB4. LTB4 receptor antagonists or LXA4 was not associated with qualitative or quantitative changes in superficial or deep dermal mononuclear cell infiltrates at the reaction site. We conclude that LTB4 modulates visible expression of DTH in vivo by a receptor-mediated mechanism.

Animals↗
PubMed1995

Twice-per-day fractionated high versus continuous low dose rate intracavitary therapy in the radical treatment of cervical cancer: a nonrandomized comparison of treatment results.

PURPOSE: To compare the efficacy of two twice-per-day fractionated high dose rate (HDR) brachytherapies with a historical control group treated with low dose rate (LDR) brachytherapy for cervical cancer patients. METHODS AND MATERIALS: From 1985 to 1988, 92 patients with cancer of the cervic were treated by remote-controlled, HDR brachytherapy, six fractions of 7 Gy per fraction (42 Gy) at point A (HDR-6). Fifty-seven patients were treated with four fractions of 8 Gy per fraction (32 Gy) at point A (HDR-4). A twice-per-day program was used for all HDR patients by two split courses. As a historical control, treatment results of 259 patients treated with LDR brachytherapy (40 Gy in two split courses) were compared with those of the two HDR regimens. All patients received whole pelvic external irradiation, 36-45 Gy (mostly 40 Gy) before brachytherapy. RESULTS: Five-year local control rates were not significantly different for the three groups (HDR-6 = 82.0%, HDR-4 = 85.5%, and LDR = 89.5%, respectively). Five-year survival rates were also comparable (67.7%, 77.9%, and 74.1%, respectively). However, late complications were lower in HDR-4 than HDR-6 (11.0% vs. 25.6%). CONCLUSIONS: Both 5-year local control and survival rates were comparable among the three groups. However, HDR-4, which was more biologically equivalent to our LDR regimen, showed fewer complications compared to HDR-6. In addition, our twice-per-day schedule shortened the hospital stay.

Adult↗
PubMed1995

Peroxynitrite-induced apoptosis in HL-60 cells.

Peroxynitrite (ONOO-), an anion and a potent oxidant, generated by the interaction of nitric oxide (NO) and superoxide is able to induce apoptosis in HL-60 human leukemia cells in a time- and concentration-dependent manner. Characteristic morphology of apoptosis can be observed 3 h after HL-60 cells are exposed to 10 microM ONOO-. Treatment of HL-60 cells with increasing concentrations of ONOO- from 1 to 100 microM confirms the concentration dependence of apoptosis as evidenced by: 1) degradation of nuclear DNA of these cells into integer multiples of approximately 200 base pairs; 2) colorimetric DNA fragmentation assay; and 3) evidence of condensation of chromatin and nuclear fragmentation shown by propidium iodide staining. Under the same conditions, peroxynitrite causes apoptosis in another transformed cell line, U-937 cells, but is ineffective at inducing apoptosis in normal endothelial cells derived from human umbilical cord and normal human peripheral blood mononuclear cells. This direct evidence of peroxynitrite inducing apoptosis implicated a new function of this potent oxidant.

Apoptosis↗
PubMed1994

The study of anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with systemic lupus erythematosus and central nervous system involvement.

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

Adolescent↗
PubMed1993

Measurement of anti-endothelial and anti-cardiolipin autoantibodies and intercellular adhesion molecules-1 in patients with systemic and cutaneous vasculitis.

Two types of autoantibodies and intercellular adhesion molecule-1 (ICAM-1) were measured in patients with vasculitis. There were 13 patients with systemic vasculitis, and 12 with cutaneous vasculitis. The measured antibodies included antiendothelial cell antibodies (AECA) and anti-cardiolipin (ACL) antibodies of three isotypes. Results showed that patients with systemic vasculitis had elevated levels of ICAM-1 and IgG isotype ACL antibodies. Higher levels of ICAM-1 and IgG isotype ACL antibody were found in patients with systemic vasculitis than in those with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement, and for following the disease course.

Adolescent↗