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H-M Lee

Publications and source records attributed to H-M Lee.

8 recordsLinked to original sources

Serotonergic pre-treatments block in vitro serotonergic phase shifts of the mouse suprachiasmatic nucleus circadian clock.

The suprachiasmatic nucleus (SCN) contains a circadian clock that maintains its time-generating and phase-modulating capacities in vitro. Previous studies report clear differences in the ability of serotonergic stimuli to phase-shift the SCN clock when applied directly to the SCN either in vivo or in vitro: while mice and rat circadian clocks are readily phase-shifted by serotonin (5-HT) or 5-HT agonists applied in vitro, hamster and mice circadian clocks respond inconsistently to 5-HT agonists injected directly into the SCN in vivo. Here we have investigated one possible explanation for these differences: that the SCN isolated in vitro experiences reduced endogenous 5-HT signaling, which increases clock sensitivity to subsequent 5-HT stimulation. For these experiments we treated mouse SCN brain slices with low concentrations of compounds that increase serotonin signaling: 5-HT, a 5-HT agonist (8-OH-DPAT), the 5-HT precursor, l-tryptophan, or the 5-HT re-uptake inhibitor, fluoxetine. Pretreatment with each of these substances completely blocked subsequent phase-shifts induced by mid-subjective day treatment with either 5-HT or 8-OH-DPAT, while they did not block phase-shifts induced by the adenylate cyclase activator, forskolin. Time-course data on l-tryptophan-induced inhibition are consistent with this treatment inducing receptor internalization, while timing of the recovery from inhibition is consistent with receptor reinsertion. Together these data support the hypothesis that SCN clock sensitivity to serotonergic phase modulation is affected by the amount of prior serotonin signaling present in the SCN, and that this signaling alters the density of surface 5-HT receptors on SCN clock neurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model.

STUDY DESIGN: Randomized study. OBJECTIVES: To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha production. SETTING: Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. METHODS: Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-alpha. RESULTS: The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-alpha in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. CONCLUSION: Thalidomide treatment before ischemic insult reduces early phase ischemia/reperfusion injury of the spinal cord in rabbits.

Animals↗

Liposomal cargo unloading induced by pH-sensitive peptides.

Amphiphilic peptides designed to have a pH-dependent conformational change and membrane activity are described. At physiologic pH, the peptides would exist in a random coil conformation, but at endosomal pH values they would switch to amphiphilic alpha-helices, disrupt membranes, and release liposomal contents. A series of peptides have been investigated that contain a high percentage of Glu residues for the pH-induced conformational switch, and Leu residues for optimal lipid binding. Circular dichroism (CD) results in aqueous and liposomal environments were performed and demonstrate a pH-dependent shift to helicity upon acidification. Liposomal release data at neutral and acidic pH, also document the success of this design strategy.

Binding Sites↗

Metastatic renal cell carcinoma presenting as epistaxis.

Metastatic tumors in the nasal and paranasal sinuses are very rare. The origin of metastatic tumors in the nasal or paranasal sinuses is often renal cancer. Renal cell carcinomas are known for their tendency to early metastasis, and symptoms due to the metastatic lesion may be the only initial manifestation. In this paper we deal with the case of a 73-year-old patient who presented with recurrent epistaxis. The presence of a primary renal cell carcinoma was recognized only after surgical removal of the metastatic tumor. The presentation, difficulties in diagnosis and treatment of this tumor are discussed, with a review of the literature.

Aged↗

Clinical analysis of extranodal non-Hodgkin's lymphoma in the sinonasal tract.

We investigated the clinical analysis of non-Hodgkin's lymphoma (NHL) of the sinonasal tract, including the survival rate and treatment outcome. Fifty patients who had previously received a diagnosis of extranodal NHL of the sinonasal cavity from May 1992 to April 2001 were included. We reviewed the patients' clinical characteristics and the survival rates, retrospectively. Of 50 patients, 49 were classified as having extranodal NK/T cell lymphoma and only one patient as having diffuse large B cell (DLBC) lymphoma according to the new WHO classification. Even though higher mortality rates were observed in patients receiving chemotherapy alone than in those receiving chemotherapy and radiation therapy in the advanced stage, the combination treatment of chemotherapy and radiation therapy failed to demonstrate a significantly higher survival rate.

Adolescent↗

A giant pyogenic granuloma in the nasal cavity caused by nasal packing.

Pyogenic granuloma is a benign, rapidly growing hemorrhagic lesion of unknown origin. This disorder, however, is obscure to many rhinologists, because the nose is a relatively rare location for the lesion. In the practice of otorhinolaryngology, nasal packing is a very common procedure for nasal bleeding and postoperative hemostasis. However, few pyogenic granulomas occurring from nasal packing have been reported in the literature. A 56-year-old man underwent nasal packing with vaseline gauze because of nasal bleeding. Two months later, a dark brown nasal tumor was found in his nasal cavity. He underwent endoscopic endonasal removal of the tumor. The pathology result showed a pyogenic granuloma. This is the third case recorded in the literature of a confirmed pyogenic granuloma occuring as a complication of nasal packing. This uncommon lesion should be considered in the differential diagnosis of a rapidly growing hemorrhagic lesion within the nasal fossa.

Bandages↗

Quantitative analysis of the velocity related pathophysiology of spasticity and rigidity in the elbow flexors.

OBJECTIVE: To quantify velocity dependent and position related properties of increased muscle tone measured during a constant velocity stretch. METHODS: Elbow flexors were vertically stretched under four different velocities (40, 80, 120, and 160 degrees /s) through a 75 degrees range of motion in 12 patients with hemiparesis, 16 with parkinsonism, and 12 normal controls. From reactive torque measurement, a linear second order model was adopted to dissociate velocity dependent viscous and velocity independent elastic components. The averaged speed dependent reflex torque (ASRT)--defined as the deviation of measured torque from baseline torque--was used to quantify the viscous component of hypertonia. Velocity sensitivity of ASRT (VASRT) and segmented ASRT (SASRT), derived from the slope of the regression line among ASRT velocity plots and from segmentations of reactive torque, respectively, were used to differentiate the increased muscle tone of spasticity and rigidity. RESULTS: ASRT and VASRT were significantly higher in both spasticity and rigidity than in normal controls. SASRT analysis showed three different position related patterns among spasticity, rigidity, and normal groups: spasticity showed progressively increasing muscle tension relative to position; rigidity showed increased (relative to the norm) but constant muscle tone over the entire stretch range; the normal control group showed a consistently low reactive torque over the entire range. CONCLUSIONS: Velocity dependence analysis indicates that rigidity and spasticity have approximately equal velocity dependent properties. For differentiating these two types of hypertonia, position dependent properties my be employed.

Adult↗

Combination gene therapy with adenoviral vector-mediated HSV-tk+GCV and IL-12 in an orthotopic mouse model for prostate cancer.

We previously demonstrated significant therapeutic activities associated with adenoviral vector-mediated Herpes Simplex Virus/thymidine kinase (AdHSV-tk) with ganciclovir (GCV) in situ gene therapy in the RM-1 orthotopic mouse prostate cancer model and interleukin-12 (AdmIL-12) in situ gene therapy in the RM-9 orthotopic mouse prostate model for prostate cancer. In both protocols, local cytotoxicity and activities against pre-established lung metastases were demonstrated. To test whether combined AdHSV-tk+GCV+IL-12 gene therapy would lead to enhanced therapeutic effects when compared to either treatment alone, we used RM-9 mouse prostate cancer cells in both orthotopic and pre-established lung metastases models of prostate cancer. Combined treatment with a single injection of optimal doses of AdHSV-tk+GCV or AdmIL-12 led to significantly increased suppression of orthotopic tumor growth. IL-12 gene therapy alone was more effective than AdHSV-tk+GCV in suppressing spontaneous lymph node metastases and pre-established lung metastases but combination gene therapy did not result in additional anti-metastatic activities. Combination gene therapy also did not achieve significantly better animal survival compared to AdHSV-tk+GCV or AdmIL-12 alone. Analysis of localized antitumor activities demonstrated that AdHSV-tk+GCV therapy induced higher levels of necrosis compared to AdmIL-12 or combination therapy. However, both treatments alone and combination therapy produced similar increases in apoptotic index. To address the possible mechanisms of locally co-operative cytotoxic activities, we analyzed the systemic natural killer (NK) response and the numbers of tumor-infiltrating immune cells using quantitative immunohistochemical analysis. AdHSV-tk+GCV therapy alone led to detectable increases in iNOS-positive cells, CD4+and CD8+T-cells and moderately increased numbers of F4/80 (macrophage selective)-positive cells within treated tumors. In contrast, AdmIL-12 elicited a highly robust pattern of tumor infiltration for all four of these immune cells that was in general mimicked by combination therapy. Further analysis of the accumulation of transforming growth factor-beta1 (TGF-beta1) immunohistochemical staining demonstrated that AdHSV-tk+GCV treatment, but not AdmIL-12 treatment, produced cancer cell-associated increases in this cytokine relative to control Ad-beta-gal injections. Interestingly, local injection with AdHSV-tk+GCV induced significant splenocyte-derived NK cell cytolytic activities with maximal response 7 days following treatment, whereas AdmIL-12 injection produced significantly higher NK activity with maximal response 2 days following injection. The combined treatment produced a higher systemic NK response over the 14-day treatment period. Depletion of NK cells in vivo demonstrated that this immunocyte subpopulation was responsible for early locally cytotoxic activities induced by AdHSV-tk+GCV but not AdmIL-12 and that NK activities were largely responsible for activities against pre-established metastases generated by both gene therapy protocols. Prostate Cancer and Prostatic Diseases (2001) 4, 44-55

Journal Article↗