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Biomedical subjects

S L Yang

Publications and source records attributed to S L Yang.

At least 73 records · Page 4Linked to original sources
PubMed1997

Differential activation of protein kinase A in various regions of myocardium during sepsis.

Changes in the activities of protein kinase A (PKA) (cAMP-dependent protein kinase) in various regions of rat myocardium during different cardiodynamic phases of sepsis were studied in an attempt to understand the pathophysiology of cardiac dysfunction during sepsis. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 hr, respectively, after CLP. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two types of PKA, Type I (eluted at low ionic strength) and Type II (eluted at high ionic strength), were collected, and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Under physiological conditions, Type I PKA activities were unevenly distributed (left atrium > right atrium > pacemaker region > left ventricle > right ventricle > ventricular septum) while Type II PKA activities were evenly distributed among different regions of myocardium. During early sepsis, Type I PKA activities remained unchanged while Type II PKA activities were activated by 32 and 70% in right atrium and pacemaker regions, respectively. During late sepsis, Type I PKA activities were stimulated by 228% in ventricular septum while Type II PKA activities were not affected. These data demonstrate that different PKA activities exist in various regions of the myocardium and that PKA activities were preferentially activated in certain areas during the progression of sepsis. Since PKA plays an important role in the regulation of myocardial function and metabolism, the activation of PKA in different regions of myocardial during different stages of sepsis may contribute to the altered cardiac function during the progression of sepsis.

Animals↗
PubMed1997

Novel patterns of p53 abnormality in breast cancer from Taiwan: experience from a low-incidence area.

Among 114 breast cancers in Taiwan, the prevalence of p53 mutation (22.8%) and p53 accumulation (38.3%) was similar to that in high-incidence areas. However, novel patterns of p53 abnormalities, including unique sites or types of mutation (i.e. an excessive proportion of G:C to A:T transition at CpG site), and accumulation of wild-type p53 either within nuclear or cytoplasmic compartments were noted. These may have relevance to breast cancer in Taiwan, a low-incidence area.

Breast Neoplasms↗
PubMed1997

Protein kinase a activity is increased in rat heart during late hypodynamic phase of sepsis.

Changes in the activities of protein kinase A (PKA, or cAMP-dependent protein kinase) in rat heart during different cardiodynamic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture. Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals killed at 9 and 18 h, respectively, after cecal ligation and puncture. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Results obtained show that during early sepsis, both type I and type II PKA activities were unaffected. During late sepsis, type I PKA activities were stimulated by 66.7-97.7%, while type II PKA activities remained constant. Kinetic analysis of the data on type I PKA during late sepsis reveals that the Vmax values for ATP, cAMP, and histone were increased by 84.7, 66.7, and 97.7%, respectively; while the Km values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA is activated in rat heart during late hypodynamic phase of sepsis. Since kinase-mediated phosphorylation plays an important role in regulating myocardial function and metabolism, an activation of type I PKA during late sepsis may contribute to the development of altered myocardial function during hypodynamic phase of sepsis.

Animals↗
PubMed1997

[Studies on chemical structures of two iso-acetogenins from Annona reticulata].

Two annonaceous acetogenins: squamone (1) and isoannonareticin (2) have been isolated from the seeds of Annona reticulata L. (Annonaceae). 1 and 2 were shown to be mixtures of 2-epimers by the successful separation of their acetates with preparative TLC, giving: 2,4-cis-squamone diacetate (1a-1), 2,4-trans-squamone diacetate (1a-2), 2,4-cis-isoannonareticin diacetate (2a-1) and 2,4-trans-isoannonareticin diacetate (2a-2). The 2,4-cis-squamone (1-1) and 2,4-trans-isoannonareticin (2-1) are new annonaceous acetogenins. Their structures and relative stereochemistry were elucidated on the basis of spectral analysis (1H-1H COSY and NOE).

Drugs, Chinese Herbal↗
PubMed1997

Experience with ifosfamide and etoposide combination chemotherapy in extensive-disease small-cell lung cancer.

BACKGROUND: Ifosfamide, an isomeric analogue of cyclophosphamide, has significant activity against many human tumors including lung cancer, testicular cancer, lymphoma and sarcoma, and may be superior to its analogue. Herein, we report our preliminary experience using ifosfamide and etoposide (IE) combination chemotherapy in previously untreated patients with extensive-disease (ED) small-cell lung cancer (SCLC). METHODS: Patients with histologically or cytologically confirmed SCLC, measurable or assessable ED, no previous chemotherapy or thoracic irradiation, younger than 70 years of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-3, and adequate marrow, liver, and renal functions were eligible for treatment which consisted of ifosfamide 2.0 g/m2/d given intravenously (i.v.) for 3 days with mesna 400 mg/m2/dose i.v. administered 0, 4, and 8 hours after the daily administration of ifosfarnide, and etoposide 80 mg/m2/d i.v. given for 3 days in every 4 weeks for a maximum of 6 cycles. RESULTS: Between January 1994 and February 1995, 10 patients were enrolled into the treatment. All were men with a mean age of 63 +/- 6 years. Five patients had an ECOG PS of 0 or 1, 4 patients of 2, and 1 patient of 3. A total of 45 cycles of IE were given. The mean number of cycles per patient was 4.5 +/- 2.1. Six patients completed 6 courses of therapy. Thirty-two of 45 cycles (71%) of IE were given at full doses, while the remaining 13 cycles (29%) were given at 75% of doses. Nine patients were assessable for response. Eight patients had a partial remission and one patient had stable disease. The overall response rate was 89%. The median survival was 8 months (range, 0 to 23 months) and the median failure-free survival duration was 5.5 months (range, 0 to 18 months). The 1- and 2-year survival rates were 30% and 0%, respectively. Myelotoxicity was the most important toxicity, particularly neutropenia, while thrombocytopenia and anemia were mild. Five of 10 patients (50%) experienced grade 4 neutropenia, which occurred in 2 patients during the first course of IE and resulted in one patient death from early sepsis. Other nonhematologic toxicities were mild. CONCLUSIONS: Our preliminary experience demonstrates that ifosfamide is an active drug against SCLC and combination chemotherapy with IE results in similar response rate and median survival, but probably higher myelotoxicity than reported studies in patients with ED SCLC.

Aged↗
PubMed1996

Molecular epidemiology of cytomegalovirus infection in kindergarten children.

This study was conducted to determine the source of cytomegalovirus (CMV) excretion in children who had persistent viruria. A total of 287 children, ages 3-5 years, enrolled in two kindergartens were followed for 9 months, and 28.8% of 139 CMV-infected children were found to have shed virus persistently in urine for > or = 3 months. A polymerase chain reaction (PCR)-based method provided direct evidence to demonstrate differences in CMV strains shed by 32 persistent shedders selected at random. The glycoprotein B (gB) nucleotide regions of CMV were amplified and analyzed by restriction enzyme digestion. The CMV strains shed by most of these children showed different restriction profiles compared with strains from their playmates. It is considered that persistent reactivation of endogenous CMV is the most plausible explanation.

Antibodies, Viral↗
PubMed1996

Previous heat shock treatment attenuates bicuculline-induced convulsions in rats.

Exposure to elevated temperature provokes a sequence of events (heat shock response) in all living organisms. Through this response, heat shock proteins (HSPs) are induced and protect the cells against subsequent injury. We investigated the effect of heat treatment on bicuculline-induced convulsions, and analyzed a possible role of HSPs. Screw electrodes were implanted in the brain of mature male Wistar rats for electroencephalogram (EEG) recording. Experimental rats were subjected to whole-body hyperthermia at 41-42 degrees C for 15 min. Fifteen hours later, bicuculline was injected intraperitoneally to induce convulsions in both experimental and control groups. The heated rats showed a significant attenuation of the convulsive response, in terms of both spike discharges in EEG and clinical seizures. Further-more, induction of HSP72 was detected in the brain of heat-treated rats by immunoblotting, appearing at 4 h and reaching a maximal level 16-24 h after the heat shock. We conclude that the previous heat treatment stabilized neuronal excitability, most probably through the induction of HSP72.

Animals↗
PubMed1996

Lupane derivatives from Lophopetalum wallichii with farnesyl protein transferase inhibitory activity.

Chloroform-soluble extracts of the stems and of the mixed stems and stem bark of Lophopetalum wallichii were found to be inhibitory in a farnesyl protein transferase (FPTase) bioassay system. During the course of activity-guided fractionation, the known lupane-type triterpenes, ochraceolide A (1), ochraceolide B (2), betulin, and lupeol and the new lupane lactone, dihydro ochraceolide A (4), were isolated. The stereochemistry of the epoxide group of ochraceolide B (2) was determined by preparation of both epoxide isomers [2, and the new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The structure of 4 was established by reduction of 1 with sodium borohydride. Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay (IC50 values of 1.0 and 0.7 microgram/mL, respectively). Lupeol was found to be weakly active (IC50 65.0 micrograms/mL) in this test system, whereas no significant inhibition was detected for betulin or compounds 3 or 4. When evaluated against a panel of human cancer cells in culture, compounds 1 and 4 were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.

Alkyl and Aryl Transferases↗
PubMed1996

Estradiol modulation of neuron loss in the medial division of medial preoptic nucleus in rats during aging.

The age-related morphological changes in the darkly stained sex-dimorphic nucleus (SDN-POA) and the lighter staining surrounding area (non-SDN-POA) within the medial division of preoptic nucleus of Long-Evans rats were studied. The long-term effects of estradiol benzoate (EB) on the changes were also assessed. During aging, the neuron loss in 14-(middle-age) and 22-month-old rats as well as increased pyknotic ratio of neurons in old male rats were observed in SDN-POA, but not in the non-SDN-POA. In female rats, significant neuron loss with advancing age was observed both in SDN-POA and the non-SDN-POA. Neuron loss in SDN-POA of EB-treated males was more severe than that of the intact males, while no significant difference of neuron loss was observed between EB-treated and age-matched intact female rats. However, neuron loss in SDN-POA of ovariectomized female rats was more severe than that of the age-matched intact females. These results indicate that age-related neuron loss in medial preoptic nucleus show sex-specific and area-specific features, and estradiol may play a important role in modulating neuron loss during aging.

Aging↗
PubMed1996

Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein.

In the prion diseases, extensive reactive gliosis is often found to be out of proportion to the degree of apparent neuronal damage. To evaluate the role of astrocytic gliosis in experimental scrapie of the mouse, we inoculated mice deficient in apolipoprotein E (apoE) or the glial fibrillary acidic protein (GFAP) with mouse prions. The expression of both apoE and GFAP in astrocytes increases as part of the reactive gliosis that accompanies scrapie. Null mice deficient in either apoE or GFAP inoculated with prions exhibited incubation times indistinguishable from untargeted control mice. The level of PrPSc and its regional deposition in the brains of ill mice deficient in either protein were also similar to control mice. Our findings demonstrate that neither apoE nor GFAP participates in the pathogenesis of the disease or in the production of PrPSc.

Animals↗
PubMed1996

I-cell disease: report of a case.

I-cell disease, or mucolipidosis type II (ML II), resembles Hurler syndrome but without the mucopolysacchariduria. I-cell disease is a slowly progressive disorder with onset at birth and fatal outcome in childhood. The neonate with I-cell disease usually has a low birth weight. Unlike Hurler syndrome, there is no temporary acceleration of skeletal growth around one year of age. Instead, clinical characteristics included coarse face and skin, skeletal abnormalities, gum hypertrophy, and severe psychomotor retardation. Head size is proportional to stature. Psychomotor retardation is extreme in some patients but rather mild in others. The most frequent causes of death are bronchopneumonia and congestive heart failure. We report a 9 month-old male infant with characteristic clinical features of I-cell disease. Cytoplasmic inclusions were observed in cultured skin fibroblasts. Ultrastructural study of normal looking skin revealed numerous cytoplasmic inclusions with pleomorphic contents in the fibroblasts and Schwann cells. The diagnosis was confirmed by lysosomal enzyme assay in serum and fibroblasts.

Clinical Enzyme Tests↗
PubMed1996

Augmentation of TNF-alpha production, NK cell activity and IL-12 p35 mRNA expression by methionine enkephalin.

AIM: To study the host immune surveillance functions by the neuropeptide methionine enkephalin (met-enk). METHODS: To measure the effects of met-enk on NK activity, the production and gene expression of anti-tumor cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) in vitro and in vivo. RESULT: Met-enk promoted NK activity at 1 x 10(-8) - 1 x 10(-5) mol.L-1, increased TNF-alpha production both in vitro and in vivo, and enhanced IL-12 p35 gene transcription after ip 0.1 mg.kg-1 for 6 d. CONCLUSION: The up-regulating effects of met-enk contribute to the host neuro-immunomodulating mechanism against tumors and invading antigens. Enkephalins and endorphins were originally described as the endogenous ligands for the morphine receptors in the brain. In addition to their central nervous activity, an immunomodulating action of the enkephalins was first reported in 1979. Methionine enkephalin (met-enk) regulated a variety of immunological responses, including enhancing the proliferation of human peripheral lymphocytes and mouse spleen cells, regulating antibody production, natural killer cells (NK) activity and synthesis of a number of cytokines. These results suggested that met-enk might be used to elevate the body resistance to cancer and other diseases, or diminish autoimmune responses which are detrimental to host. To elucidate that met-enk has the activity of anti-tumor through related immune regulating responses, this study is to investigate the effects of met-enk on immune surveillance and immune defence functions.

Animals↗
PubMed1995

Liver protein kinases in shock: I. Endotoxin administration inactivates protein kinase a in dog liver.

Effects of endotoxin administration on protein kinase A (cAMP-dependent protein kinase) activity in dog liver were investigated. Hepatic protein kinase A was extracted and partially purified by acid precipitation, ammonium sulfate fraction, and DEAE-cellulose chromatography. Protein kinase A was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of protein kinase A, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected, and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. The results obtained 4 h after endotoxin administration (.5 mg/kg, intravenously) show that type I protein kinase A activity was unaffected, while type II protein kinase A activity was inhibited by 26-57%. Kinetic analysis of the data on type II protein kinase A reveals that the Vmax values for ATP, cAMP, and histone were decreased by 31, 39, and 36%, respectively; while the S.5 (substrate concentration required for half-maximal enzyme activity) values for ATP, cAMP, and histone were unaffected following endotoxin administration. These data indicate that endotoxin administration inhibits hepatic type II protein kinase A activity and the nature of inhibition is by a mechanism not competing with ATP, cAMP, and histone reactive sites. Since protein phosphorylation plays an important role in the regulation of cell metabolism and function, our finding may contribute to the understanding of hepatocellular dysfunction during endotoxin shock.

Animals↗
PubMed1995

Methionine-enkephalin augments interleukin-6 production and gene expression.

AIM: To study the effect of methionine-enkephalin (met-enk) on the production and gene expression of interleukin-6 (IL-6) both in vivo and in vitro. METHODS: IL-6 was assayed using its dependent cell line MH60.BSF2 and measured by MTT spectrophotometry. IL-6 gene expression was proceeded by RNA isolation and hybridization with IL-6 cDNA. RESULTS: Met-enk stimulated IL-6 mRNA expression and increased its stability. Met-enk 0.1 and 1 mg.kg-1 ip for 6 d enhanced serum IL-6 levels. CONCLUSION: An up-regulation of IL-6 by met-enk was mediated through an increase in transcriptional activity and stability of IL-6 mRNA.

Animals↗
PubMed1995

[Tyr-D-Ala-Gly-Phe-D-Leu (DADL) solid-phase synthesis and its effects on immune function].

DADL, a delta-receptor selective enkephalin analogue, was prepared with the technique of solid-phase peptide synthesis. It was found to stimulate directly the proliferation of mouse splenic lymphocytes dose-dependently. However, synergistic effect of DADL at different concentrations with ConA and LPS were not found. In addition, TNF-alpha production was increased by ip DADL (1.0 mg.kg-1 x 6 d) in mice and the production of LPS-induced TNF-alpha in mouse peritoneal macrophages was enhanced after DADL was added in vitro. These results suggest that DADL, like enkephalins, exerts some immunoregulatory activities.

Adjuvants, Immunologic↗
PubMed1994

Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.

Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrPSc (where PrPSc is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrPSc. The patterns of MHu2MPrPSc and MoPrPSc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease > 500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.

Animals↗