Biomedical subjects

David D Kim

Publications and source records attributed to David D Kim.

7 recordsLinked to original sources

PubMed2006

Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension.

Danshen, a Chinese herb, reduces hypertension in Oriental medicine. We hypothesized that Danshen acts partially through endothelial nitric oxide synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone II(A), an active ingredient of Danshen, and the two-kidney, one-clip renovascular hypertension model in hamsters. Oral tanshinone (50 microg/100 g body wt) reduced mean arterial pressure (MAP) from 161.2 +/- 6.9 to 130.0 +/- 7.8 mmHg (mean +/- SE; P < 0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3 +/- 9.2 mmHg. Topical tanshinone at 1 microg/ml and 5 microg/ml increased normalized arteriolar diameter from 1.00 to 1.25 +/- 0.08 and 1.57 +/- 0.11, respectively, and increased periarteriolar nitric oxide concentration from 87.1 +/- 11.3 to 146.9 +/- 23.1 nM (P < 0.05) at 5 microg/ml in hamster cheek pouch. N(G)-monomethyl-L-arginine inhibited tanshinone-induced vasodilation. Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone prevented the hypertension-induced reduction of eNOS and increased eNOS expression to levels higher than sham-operated control in hamster cheek pouch. Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47 +/- 0.08 in the cremaster muscle of control mice and to 1.12 +/- 0.13 in cremasters of eNOS knockout mice. In ECV-304 cells transfected with eNOS-green fluorescent protein, tanshinone increased eNOS protein expression 1.35 +/- 0.05- and 1.85 +/- 0.07-fold above control after 5-min and 1-h application, respectively. Tanshinone also increased eNOS phosphorylation 1.19 +/- 0.07- and 1.72 +/- 0.20-fold relative to control after 5-min and 1-h application. Our data provide a basis to understand the action of a Chinese herb used in alternative medicine. We conclude that eNOS stimulation is one mechanism by which tanshinone induces vasodilation and reduces blood pressure.

Animals↗

PubMed2006

Retrovirus-mediated over-expression of decay-accelerating factor rescues Crry-deficient erythrocytes from acute alternative pathway complement attack.

Decay-accelerating factor (DAF) and complement receptor 1-related gene/protein y (Crry) are two membrane-bound complement regulators on murine erythrocytes that inhibit C3/C5 convertases. Previously, we found that Crry- but not DAF-deficient erythrocytes were susceptible to alternative pathway complement-mediated elimination in vivo. To determine whether it is a unique activity or a higher level expression of Crry makes it indispensable on murine erythrocytes, we over-expressed DAF on Crry-deficient (Crry(-/-)) erythrocytes by retroviral vector-mediated DAF gene transduction of bone marrow stem cells. DAF retrovirus-transduced erythrocytes expressed 846 +/- 127 DAF molecules/cell (DAF(high)) compared with 249 +/- 94 DAF molecules/cell (DAF(low)) and 774 +/- 135 Crry molecules/cell on control mouse erythrocytes. DAF(high)-Crry(-/-) erythrocytes were significantly more resistant than either DAF(low)-Crry(-/-), DAF(-/-) -Crry(+/+) or wild-type erythrocytes to classical pathway complement-mediated C3 deposition in vitro. Furthermore, increased DAF expression rescued Crry(-/-) erythrocytes from acute alternative pathway complement attack in vivo. Notably, long term monitoring revealed that DAF(high)-Crry(-/-) erythrocytes were still more susceptible than wild-type erythrocytes to complement-mediated elimination as they had a shorter half-life in complement-sufficient mice but survived equally well in complement-deficient mice. These results suggest that both a high level expression and a more potent anti-alternative pathway complement activity of Crry contributed to its indispensable role on murine erythrocytes. Additionally, they demonstrate the feasibility of using stem cell gene therapy to correct membrane complement regulator deficiency on blood cells in vivo.

Animals↗

PubMed2006

De novo head and neck carcinoma in transplant recipients: preliminary results of management.

PURPOSE: To evaluate the stage-based definitive management approach of de novo head and neck cancer (HNC) developing in immunocompromised transplant recipients. PATIENTS AND METHODS: A retrospective analysis was performed on 5 patients with HNC who had previously received an organ or bone marrow transplant. Surgery, radiotherapy, and chemotherapy (alone or in combination) were the employed therapeutic methods for stage I to IV HNC. RESULTS: At diagnosis of HNC, the average patient age was 60 years. The average interval between transplantation and the appearance of HNC was 5 years. In addition to immunosuppressive therapy, 4 patients had another risk factor for HNC development-long history of smoking; also, another person was treated by total body irradiation. With appropriate management that included local treatment for early-stage disease and bimodal therapy in cases of locally advanced neoplasms, all patients (4 being tumor-free) were alive at 6 to 38 months' follow-up. CONCLUSION: Although longer follow-up information is needed, we contend that judicious stage-based management of HNC in transplant recipients is associated with outcomes not necessarily different from patients who are not immunosuppressed.

Aged↗

PubMed2005

Membrane complement regulatory proteins.

A number of proteins anchored on the cell surface function to protect host tissues from bystander injury when complement is activated. In humans, they include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46), complement receptor 1 (CR1, CD35) and CD59. Although disease conditions directly attributable to abnormal function of these proteins are relatively rare, it has become evident from recent studies using animal models that membrane complement regulatory proteins are important modulators of tissue injury in many autoimmune and inflammatory disease settings. Evidence is also emerging to support a role of these proteins in regulating cellular immunity. In this article, we highlight recent advances on the in vivo biology of membrane complement regulatory proteins and discuss their relevance in human disease pathogenesis and therapeutics.

Animals↗

PubMed2005

Neonatal group B streptococcus sepsis after negative screen in a patient taking oral antibiotics.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of serious neonatal infection. Neonatal morbidity and mortality can be reduced by appropriate prenatal screening and intrapartum chemoprophylaxis. CASE: A 20-year-old primigravida was treated with oral antibiotics at 35 weeks for a recurrent urinary tract infection. Her GBS screen following the antibiotic treatment showed a negative culture. The patient, therefore, did not receive intravenous antibiotics during her induction of labor for mild preeclampsia. The infant developed early onset neonatal GBS pneumonia and sepsis. CONCLUSION: Oral antibiotics can cause a temporary negative culture in a GBS-colonized patient. Relying on a negative culture for management may not be appropriate in a patient treated with oral antibiotics. Additional studies are necessary to elucidate the effects of oral antibiotics on GBS.

Administration, Oral↗

PubMedDate not supplied

Inhibition of topoisomerase II in 32D.3(G) cells by hydroquinone is associated with cell death.

Studies showing the inhibition of isolated human topoisomerase II (topo II) by benzene metabolites such as hydroquinone, coupled with the recognition that benzene-induced acute myelogenous leukemia bears a resemblance to second cancers caused by topo II inhibitors such as etoposide, suggested that topo II inhibition by hydroquinone might induce leukemogenic mutations. In these studies the inhibition of topo II by hydroquinone or etoposide was studied in parallel with the effects of these agents on differentiation, maturation and viability in murine bone marrow 32D.3(G) cells. Topoisomerase II of 32D.3(G) cells was inhibited by hydroquinone at concentrations of 5 micro M or higher and by etoposide at concentrations of 50 micro M or higher. At concentrations of either agent below those that inhibited topo II the cells responded normally to interleukin-3, which promoted proliferation, and to granulocyte colony-stimulating factor, which promoted differentiation and maturation. In dose ranges in which topo II was inhibited by either hydroquinone or etoposide, the cells became progressively less viable and cell counts decreased during the incubation period. Progressive inability to detect topo II protein by Western blot analysis as hydroquinone concentrations were increased suggested that either association of the probe with the enzyme was inhibited by hydroquinone or there was degradation of the protein as a function of hydroquinone-induced apoptosis.

Animals↗

PubMedDate not supplied

Acupuncture reduces experimental renovascular hypertension through mechanisms involving nitric oxide synthases.

OBJECTIVE: To test the hypothesis that acupuncture on stomach 36 point (ST-36) reduces hypertension by activating nitric oxide synthase signaling mechanisms. METHODS: The authors used the two-kidney, one-clip renal hypertension (2K1C) hamster model with electroacupuncture treatment. RESULTS: Thirty-minute daily electroacupuncture treatment for 5 days reduced mean arterial pressure from 160.0 +/- 7.6 to 128.0 +/- 4.3 mmHg (mean +/- SEM), compared to 115.0 +/- 7.2 mmHg in sham-operated hamsters. Electroacupuncture increased periarteriolar NO concentration from 309.0 +/- 21.7 nM to 417.9 +/- 20.9 nM in the 2K1C hamster cheek pouch microcirculation when measured with NO-sensitive microelectrodes. Hypertension reduced endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) proteins relative to the sham-operated control, as measured by Western blotting. Electroacupuncture prevented the reduction of eNOS and nNOS associated with hypertension and showed even higher eNOS and nNOS expressions than sham-operated control in stomach and cheek pouch tissues, which are on the stomach meridian. Analysis of liver tissue, a non-stomach-meridian organ, indicated that electroacupuncture did not have a significant benefit in terms of enhanced expressions of eNOS and nNOS in the treated 2K1C hypertensive group. CONCLUSIONS: Activation of eNOS and nNOS is one of the mechanisms through which ST-36 electroacupuncture reduces blood pressure; this reduction works through the stomach meridian.

Acupuncture Points↗