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Biomedical subjects

N Lin

Publications and source records attributed to N Lin.

At least 19 recordsLinked to original sources

Dendritic plasticity of CA1 pyramidal neurons after transient global ischemia.

Dendrites and spines undergo dynamic changes in physiological conditions, such as learning and memory, and in pathological conditions, such as Alzheimer's disease and epilepsy. Long-term dendritic plasticity has also been reported after ischemia/hypoxia, which might be compensatory effects of surviving neurons for the functional recovery after the insults. However, the dendritic changes shortly after ischemia, which might be associated with the pathogenesis of ischemic cell death, remain largely unknown. To reveal the morphological changes of ischemia-vulnerable neurons after ischemia, the present study investigated the alteration of dendritic arborization of CA1 pyramidal neurons in rats after transient cerebral ischemia using intracellular staining technique in vivo. The general appearance of dendritic arborization of CA1 neurons within 48 h after ischemia was similar to that of control neurons. However, a dramatic increase of dendritic disorientation was observed after ischemia with many basal dendrites coursed into the territory of apical dendrites and apical dendrites branched into the region of basal dendrites. In addition, a significant increase of apical dendritic length was found 24 h after ischemia. The increase of dendritic length after ischemia was mainly due to the dendritic sprouting rather than the extension of individual dendrites, which mainly occurred in the middle segment of the apical dendrites. These results reveal a plasticity change in dendritic arborization of CA1 neurons shortly after cerebral ischemia.

Animals↗

Large dose ketamine inhibits lipopolysaccharide-induced acute lung injury in rats.

BACKGROUND: Sepsis is associated with the highest risk of progression to acute lung injury or the acute respiratory distress syndrome. Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. Our study was designed to investigate the effect of ketamine on the endotoxin-induced acute lung injury in vivo. MATERIALS AND METHODS: Adult male Wistar rats were randomly divided into 6 groups: saline controls; rats challenged with endotoxin (5 mg/kg) and treated with saline; challenged with endotoxin (5 mg/kg) and treated with ketamine (0.5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (50 mg/kg); saline injected and treated with ketamine (50 mg/kg). TNF-alpha, IL-6 and NF-kappa B were investigated in the tissues of the lung after 2 h. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated 6 h later. RESULTS: We demonstrated that intravenous administration of endotoxin could provoke significant lung injury, which was characterized by increase of MPO activity and wet/dry weight ratio, TNF-alpha and IL-6 expression and NF-kappa B activation. Ketamine (5, 50 mg/kg) inhibited endotoxin-induced NF-kappa B activation. Ketamine only at a dose of 50 mg/kg inhibited TNF-alpha and IL-6 production, and decreased MPO activity and wet/dry weight ratio after endotoxin challenge. CONCLUSIONS: Ketamine, only at a supra-anesthetic dosage, could inhibit endotoxin-induced pulmonary inflammation in vivo.

Animals↗

Methemoglobinemia misdiagnosed as ruptured ectopic pregnancy.

A 22-year-old woman with an initial diagnosis of 'ruptured ectopic pregnancy' and 'hemorrhagic shock' was sent to the operation room for surgical treatment. The mucocutaneous color was deeply cyanosed and the pulse oximeter oxygen saturation (SpO2) was only 86% after tracheal intubation (100% O2). 'Chocolate-brown' blood was observed and methemoglobinemia was considered. Then the arterial blood gas (ABG) sample was obtained, an intravenous infusion of methylene blue and vitamin C followed. The patient recovered quickly, and later two other patients with similar symptoms were treated in the same way. The success was due to a correct diagnosis accompanied with prompt treatment and quick recognition of the etiology.

Adult↗

Temperature dependence of the surface anisotropy of Fe ultrathin films on Cu(001).

We report an experimental approach to separate temperature dependent reversible and irreversible contributions to the perpendicular magnetic anisotropy of Fe films grown at low temperatures on Cu(001) substrates. The surface anisotropy K(S)(T) is found to decrease linearly with temperature, causing a thermally induced spin reorientation into the plane. The irreversible shift of the spin reorientation transition and the coercivity of the iron films are directly correlated to the increasing Fe island size during annealing. The increased coercivity is discussed in terms of domain wall energy inhomogeneities provided by the islands.

Journal Article↗

Therapy-related myelodysplastic syndrome after autologous stem cell transplantation for breast cancer.

Therapy-related myelodysplastic syndrome and acute myelogenous leukemia (t-MDS/AML) are serious complications of chemotherapy and radiotherapy for cancer. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may be associated with an increased incidence of these complications. The frequency of t-MDS/AML after ASCT for breast cancer is uncertain. We reviewed our database of 379 consecutive breast cancer ASCT patients treated with alkylator-based chemotherapy, followed for a median of 1.52 years (range 0-8.97), with a median survival of 6.16 years. Three patients have developed tMDS/AML. The probability of developing this complication at 5 years is 0.032 in our series. We have used pathologic, cytogenetic and molecular methods to evaluate which portions of therapy may have predisposed to the development of this complication. Cytogenetic abnormalities were not found in the stem cell harvests of these patients by metaphase analysis or by fluorescence in situ hybridization (FISH). One patient demonstrated a clonal X chromosome inactivation pattern in her stem cell harvest, indicating pre-transplant chemotherapy may have been responsible for the development of her leukemia. As two of our patients developed this complication at greater than 4 years post-transplant, the number of cases may increase with longer follow-up. While the incidence appears to be low, further prospective and retrospective analysis will be necessary to determine which portions of therapy predispose to the development of t-MDS/AML in patients undergoing ASCT for treatment of breast cancer.

Acute Disease↗

Metabolic oscillations in an E. coli fermentation.

Recombinant E. coli fermentations were observed to undergo regular, reproducible oscillations in oxygen uptake for several hours during a controlled fermentation process. Culture growth slowed during the period of oscillations, delaying induction of recombinant protein production. The oscillations were similar in 10-L and 1,000-L fermentors and also occurred with different feed control algorithms. Both observations support the hypothesis that the oscillations are metabolic in nature. Analysis of amino acid, ATP, and GTP pools suggests that the oscillations result from aberrant regulation of isoleucine biosynthesis leading to repeated starvation events in which protein synthesis and growth are impaired. Both a nutritional solution, isoleucine feeding, and a genetic solution, repair of an ilvG frameshift mutation in E. coli K-12 strains, were found to eliminate the oscillations, further supporting the proposed mechanism for the behavior. These results illustrate the interesting and complicated physiological behavior which can be displayed in metabolic networks and provide another example of surprising problems that can arise in growing recombinant organisms in fermentors.

Adenosine Triphosphate↗

Studies on reactions of oxidizing sulfur-sulfur three-electron-bond complexes and reducing alpha-amino radicals derived from OH reaction with methionine in aqueous solution.

The technique of pulse radiolysis with spectrophotometric detection has been used to investigate the possibility of electron transfer reactions between oxidizing sulfur-sulfur three-electron-bond complexes (Met2/S thereforeS+), or reducing alpha-amino radicals (CH3SCH2CH2CH.NH2) derived from reaction of methionine with OH radicals and hydroxycinnamic acid (HCA) derivatives, riboflavin (RF) or flavin adenine dinucleotide (FAD), respectively. The HCA derivatives, such as caffeic acid, ferulic acid, sinapic acid and chlorogenic acid, widely distributed phenolic acids in fruit and vegetables, have been identified as good antioxidants previously can rapidly and efficiently repair oxidizing three-electron-bond complexes via electron transfer. RF and FAD can oxidize reducing alpha-amino radicals derived from methionine. The electron transfer rate constants approximately 10(9) dm3 x mol(-1)x s(-1) were determined by following the build-up kinetics of species produced.

Antioxidants↗

A kinetic study on the interaction of deprotonated purine radical cations with amino acids and model peptides.

By use of pulse radiolysis techniques, the radical cations of purine nucleotides have been successfully produced by the SO4- ion oxidation. Time-resolved spectroscopic evidence is provided that the one-electron-oxidized radicals of dAMP and dGMP can be efficiently repaired by aromatic amino acids (including tyrosine and tryptophan) via electron transfer reaction. As a model peptide, Arg-Tyr-AcOH was also investigated with regard to its interaction with deprotonated purine radical cations. The rate constants of the electron transfer reactions were determined to be (1 approximately 5) x 10(8) dm(3) mol(-1) s(-1). These results suggest that the aromatic amino acids in DNA-associated proteins may play some role in electron transfer reactions through DNA.

Amino Acids↗

Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts.

OBJECTIVE: Various extracts of the Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) have been reported to be therapeutically efficacious in rheumatoid arthritis (RA) in China, but their mechanism of action remains unclear. We investigated the effect of triptolide, a diterpenoid triepoxide from TWHF, on the production of pro-matrix metalloproteinase 1 (proMMP-1; or procollagenase 1 or pro-interstitial collagenase 1), proMMP-3 (or prostromelysin 1), tissue inhibitors of metalloproteinases (TIMPs), and proinflammatory cytokines in human synovial fibroblasts and J774A.1 mouse macrophages. METHODS: Human synovial fibroblasts and mouse macrophages were cultured with interleukin-1alpha (IL-1alpha) or lipopolysaccharide (LPS) in the presence or absence of triptolide. The production of proMMPs 1 and 3, TIMPs 1 and 2, cyclooxygenase 1 (COX-1) and COX-2, prostaglandin E2 (PGE2), IL-1beta, and IL-6 was assayed by Western blot analysis and enzyme-linked immunosorbent assay. Gene expression of proMMPs 1 and 3, TIMPs 1 and 2, COX-1 and COX-2, IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNFalpha), and IL-6 was also monitored by Northern blot analysis and reverse transcriptase-polymerase chain reaction. RESULTS: Triptolide suppressed the IL-1alpha-induced production of proMMPs 1 and 3 and decreased their messenger RNA levels in human synovial fibroblasts. In contrast, the IL-1alpha-induced gene expression and production of TIMPs 1 and 2 were further augmented by triptolide in the synovial cells. Triptolide also inhibited the IL-1alpha-induced production of PGE2 by selectively suppressing the gene expression and production of COX-2, but not those of COX-1. In addition, triptolide suppressed the LPS-induced production of PGE2 in mouse macrophages. Furthermore, the gene expression of IL-1alpha, IL-1beta, TNFalpha, and IL-6, as well as the production of IL-1beta and IL-6, were inhibited by triptolide in the LPS-treated mouse macrophages. CONCLUSION: We have demonstrated for the first time that the therapeutic effects of TWHF in RA are due in part to the novel chondroprotective effect of triptolide via the direct suppression of the production of proMMPs 1 and 3 and the simultaneous up-regulation of TIMPs in IL-1-treated synovial fibroblasts. Triptolide's interference with gene expression of proinflammatory cytokines and its known inhibitory effects on PGE2 production are also probably very effective.

Anti-Inflammatory Agents, Non-Steroidal↗

The expression of Fas/FasL in peripheral blood lymphocytes and the level of IL-2 in serum of patients with condyloma acuminata.

In order to investigate the role of the expression of the Fas/FasL in peripheral blood lymphocytes (PBLC) and the level of IL-2 in serum of patients with condyloma acuminata (CA) in the immune pathogenesis of CA, flow cytometry, indirect immunofluorescence labeling and ELISA were performed to detect the expression of the apoptotic regulatory proteins Fas/FasL in PBLC and the level of IL-2 in serum of 60 patients with different course of CA. The results showed that the expression of Fas/FasL in PBLC of the group of short course in CA was significantly higher than that of the normal controls (P < 0.05); the expression of Fas, FasL in PBLC of the group of long course CA was significantly higher than that of the group of short course and the normal controls (P < 0.05 and P < 0.01, respectively); the level of IL-2 in serum of the group of short and long course CA was significantly lower than that of the group of normal controls (P < 0.01); the negative relation was revealed between the expression of Fas/FasL in PBLC and the level of IL-2 in serum of patients with CA (r = -0.76, P < 0.01). It was suggested that the abnormal apoptosis in PBLC and decreased level of IL-2 in serum of CA might play an important role in the course of CA.

Adolescent↗

A prospective, randomized study comparing percutaneous with surgical tracheostomy in critically ill patients.

OBJECTIVE: To determine the relative cost-effectiveness of percutaneous dilational tracheostomy (PDT) and surgical tracheostomy (ST) in critically ill patients. DESIGN: Prospective randomized study. SETTING: Medical, surgical, and coronary intensive care units at Barnes-Jewish Hospital, a tertiary care medical center. PATIENTS: Eighty critically ill mechanically ventilated patients requiring elective tracheostomy. INTERVENTIONS: Randomization to either PDT performed in the intensive care unit or ST performed in the operating room. MEASUREMENTS AND MAIN RESULTS: Treatment groups were well matched with respect to age (PDT, 65.44 +/- 2.82 [mean +/- se] years; ST, 61.4 +/- 2.89 years, p = Ns), gender (PDT, 45% males; ST, 47.5% males, p = NS), severity of illness (Acute Physiology and Chronic Health Evaluation II score: PDT, 16.87 +/- 0.84; ST, 17.88 +/- 0.92, p = NS), and principle diagnosis. PDT was performed more quickly (PDT, 20.1 +/- 2.0 mins; ST, 41.7 +/- 3.9 mins, p < .0001) and was associated with lower patient charges than ST (total patient charges: PDT, 1,569 dollars +/- 157 dollars vs. ST, 3,172 dollars +/- 114 dollars; equipment/supply charges: PDT, 688 dollars +/- 103 dollars vs. ST, 1,526 dollars +/- 87 dollars; professional charges: PDT, 880 dollars +/- 54 dollars vs. ST, 1,647 dollars +/- 50 dollars; p < .0001 for all). There were no differences in days intubated before tracheostomy (PDT, 12.7 +/- 1.1 days; ST, 15.6 +/- 1.9, p = .20), intensive care unit length of stay (PDT, 24.5 +/- 2.5 days; ST, 28.5 +/- 3.1 days, p = .33), or hospital length of stay (PDT 49.7 +/- 4.2 days; ST, 43.7 +/- 3.5 days, p = .28) when we compared these two techniques. CONCLUSIONS: PDT is a cost-effective alternative to ST. The reduction in patient charges associated with PDT in this study resulted from the procedure being performed in the intensive care unit, thus eliminating the need for operating room facilities and personnel. PDT may become the procedure of choice for electively establishing tracheostomy in the appropriately selected patient who requires long-term mechanical ventilation.

Cost-Benefit Analysis↗

Comparative seven-day clinical evaluation of two tooth whitening products.

A 1-week study was conducted to compare the tooth whitening efficacy of two carbamide peroxide-based products (one containing 5% carbamide peroxide and one containing 10% carbamide peroxide). In addition, the perception of transient tooth hypersensitivity associated with the use of these products was subjectively evaluated. Sixty participants took part in a double-blind, randomized, parallel clinical study. Change in tooth color was measured by chroma meter and Vita shade guide at the initiation of the study and after 7 days of product use. Color change (delta E) was calculated using the color-difference equation established by the Commission Internationale de L'Eclairage. Data concerning dental hypersensitivity was assessed by subjective panelist questionnaires administered after the day 7 recall examination. Results of the whitening data showed that there was no significant difference between the two products. After 1 week, the mean delta E for the product containing 5% carbamide peroxide was 4.43 +/- 1.89 and the mean delta E for the product containing 10% carbamide peroxide was 4.05 +/- 1.84. However, the subjective data collected on tooth hypersensitivity showed that the product containing 5% carbamide peroxide was associated with less discomfort. Of the group using the 5% carbamide peroxide product, 20% reported transient sensitivity of their teeth after product use for 1 week compared with 53% of the group using the product with 10% carbamide peroxide. Statistical analysis using a 2-tailed t test showed significant differences between the two groups (P < .05). The data suggest that these products are clinically equivalent for tooth whitening; however, the product containing 5% carbamide peroxide was associated with less tooth hypersensitivity after 1 week of application.

Adult↗

[The clonal origin of the myeloma cells secreting three kinds of immunoglobulin from a multiple myeloma patient].

OBJECTIVE: To explore the clonal origin of myeloma cells from a multiple myeloma (MM) patient with 3 kinds of immunoglobulin (Ig). METHODS: Six primers for IgH variable region gene families VH1-VH6 and one primer of common join region (J) were used to perform reverse transcriptase polymerase chain reaction(RT-PCR). Five oligonucleotides of constant region gene (C mu, C delta, C gamma, C alpha and C epsilon) were also used as reverse primers. Different combination of primers were used to perform PCR. PCR products of IgH gene rearrangement were cloned and sequenced. RESULTS: A sharp and dense gene band appeared by using Ig VH3 gene family primer and J primer. The specific IgH gene bands also appeared by using primers of VH3 with C mu and C gamma and C alpha but not by primers of VH1, VH2, VH4, VH5 with J as well as VH3 with C delta and C epsilon. It indicated that there were IgM, IgG and IgA gene rearrangement. These gene products were cloned and sequenced. All 3 IgM, IgG and IgA gene sequences are identical. CONCLUSION: Despite the oligoclonality of MM cell, the sequencing results of 3 IgH genes showed that all the malignant cells were monoclonal origin.

Base Sequence↗

In vitro studies of cellular and molecular developmental toxicity of adjuvants, herbicides, and fungicides commonly used in Red River Valley, Minnesota.

Recent epidemiologic studies showed increased frequency of birth defects in pesticide applicators and general population of the Red River Valley, Minnesota. These studies further indicated that this crop growing area used more chlorophenoxy herbicides and fungicides than elsewhere in Minnesota. Based on frequency of use and known biology, certain herbicides, pesticide additives, fungicides, and mycotoxins are suspect agents. To define whether these agents affect developmental endpoints in vitro, 16 selected agrochemicals were examined using the MCF-7 breast cancer cell line. In the flow cytometric assay, cell proliferation in this estrogen-responsive cell line indicates xenobiotic-mediated estrogenic effects. Cell viability, morphology, ploidy, and apoptosis were incorporated in this assay. Data showed that the adjuvants X-77 and Activate Plus induced significant cell proliferation at 0.1 and 1 microg/ml. The commercial-grade herbicides 2,4-D LV4 and 2,4-D amine induced cell proliferation at 1 and 10 microg/ml. The reagent-grade 2,4-D products failed to induce proliferation over the same concentration range, suggesting that other ingredients in the commercial products, presumably adjuvants, could be a factor in these results. The fungicides triphenyltin and mancozeb induced apoptosis at concentrations of 4.1 microg/ml (10(-5) M) and 50 microg/ml, respectively. Triphenyltin also induced aneuploidy (C2/M arrest) at 0.41 microg/ml (10(-6) M). Data provide a mechanistic step to understanding human reproductive and developmental effects in populations exposed to these agrochemicals, and initiative to focusing limited resources for future in vivo animal developmental toxicity studies.

2,4-Dichlorophenoxyacetic Acid↗

Reaction of reducing hydroxyl radical adducts of pyrimidine nucleotides with riboflavin and flavin adenine dinucleotide (FAD) via electron transfer: a pulse radiolysis study.

Using the techniques of pulse radiolysis with time-resolved spectrophotometric detection, it has been demonstrated that the interaction of reducing OH radical adducts of dCMP, TMP and UMP with riboflavin (RF) and flavin adenine dinucleotide (FAD) does proceed via an electron transfer reaction. From buildup kinetics of radical species, the rate constants of electron transfer from reducing OH adducts of pyrimidines to RF and FAD have been determined, respectively. It could be deduced that RF and FAD would reduce the probability of repair of the damaged DNA in the presence of enzymes and antioxidants, accordingly RF and FAD might have a radiosensitization effect on DNA damage.

DNA↗

Tyrosine 462 of the membrane-proximal F'-G' loop of murine Mpl is not essential for high-affinity binding of thrombopoietin.

The ligand binding site of Mpl, the thrombopoietin (Tpo) receptor, has not been determined. Tyr(462)of murine Mpl corresponds to Tyr(421)of the common beta chain of the human IL-3, IL-5 and GM-CSF receptors. Tyr(421)has been identified as essential for high-affinity ligand binding. To determine whether Tyr(462)is similarly required for Tpo binding, wild-type murine Mpl (Mpl-WT) or mutant receptors containing an alanine (Y462A) or lysine (Y462K) in place of Tyr(462)were expressed in BaF3 cells. In proliferation studies, the Y462A mutation had no effect on Tpo-induced growth. In contrast, the Y462K mutation led to an attenuated proliferative response to Tpo. In single-point binding studies, both Mpl-WT and Y462A cells were able to bind [(125)I]Tpo in a specific manner. In contrast, there was a marked reduction in binding of [(125)I]Tpo by Y462K cells. Mpl-WT cells bound Tpo with a K(d)of approximately 330 pM, while Y462A cells bound Tpo with a K(d)of approximately 268 pM. The binding affinity of Y462K cells was below that quantifiable by Scatchard analysis. This study suggests that unlike the corresponding Tyr(421)of the common human beta chain, Tyr(462)of murine Mpl is not required for high-affinity ligand binding, although it may be located in proximity to the ligand binding site.

Amino Acid Sequence↗

Selenium causes growth inhibition and apoptosis in human brain tumor cell lines.

We examined the effect of the trace element selenium on human glioma cell lines: T98G, U373MG, and U87MG, in addition to dermal fibroblast cells. Cultures were incubated with sodium selenite, and the following parameters were studied: cell growth, mitochondrial function, and ultrastructure. Cell growth was assayed by counting the number of viable cells after treatment with selenium. Mitochondrial function was analyzed using the MTT (tetrazolium salt reduction) assay. Apoptosis was determined by evaluating nuclear chromatin condensation by electron microscopy. The results indicated that selenium had a significant inhibitory effect on the growth of the tumor cells but had little effect upon dermal fibroblasts which had been passaged numerous times. Selenium also induced mitochondrial damage as shown by MTT assay in two brain tumor cell lines and in minimally passaged fibroblasts, but it had little effect upon the high-passage fibroblasts. Ultrastructurally, mitochondria had electron-dense inclusions resulting from selenium treatment. High rates of apoptosis were induced by selenium in the tumor cell lines and in the minimally passaged fibroblasts, whereas the fibroblasts with a high number of passages had some resistance to selenium treatment. This study correlates the adverse effects of selenium on mitochondrial function, inhibition of cell growth, and apoptosis and shows that selenium similarly affects three different brain tumor cell lines and minimally passaged fibroblasts. Further, the results with fibroblasts show that some types of cells after repeated passages can develop resistance to selenium damage.

Apoptosis↗

A cross-cultural comparison of depressive symptom manifestation: China and the United States.

This study compared depressive symptomatology among Chinese psychiatric outpatients versus the general Chinese population, and across 3 cultural groups--Chinese, Chinese American, and Caucasian American students--by use of the Center for Epidemiological Studies-Depression Scale (CES-D; L. S. Radloff, 1977) and the Chinese Depression Scale (N. Lin, 1989), translated from the CES-D. Results indicate that Chinese patients (n = 112) endorsed a higher proportion of somatic symptoms than nonpatients (n = 112). The intercultural comparison found that Chinese students (n = 98) had the lowest levels of somatic depressive symptom endorsement compared to both U.S. groups (n = 198). These findings seem to suggest that the tendency toward somatic symptom reporting is not any greater among Chinese populations but may be a function of having a mental illness or of help seeking in China.

Adult↗