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Biomedical subjects

S S Lee

Publications and source records attributed to S S Lee.

At least 19 recordsLinked to original sources
PubMed1995

Induction of liver cytochrome P450 2B1 by beta-ionone in Sprague Dawley rats.

Induction of liver cytochrome P450 2B1 by beta-ionone was investigated in male and female Sprague Dawley rats. Administration of beta-ionone subcutaneously 72 and 48 hr before sacrificing the animals not only significantly induced the liver microsomal activity of pentoxyresorufin O-dealkylase, but also clearly increased in the level of cytochrome P450 2B1 protein. The induction of cytochrome P450 2B1 by beta-ionone was much greater in male rats than in female rats. A slot blot analysis showed that the mRNA level was increased from 6 hr after treatment with beta-ionone in male rats and from 12 hr after treatment in female rats. Taken together, the present results indicate for the first time that the induction of cytochrome P450 2B1 by beta-ionone might be regulated by the accumulation of mRNAs.

Animals↗
PubMed1995

A serpin from human tumor cells with direct lymphoid immunomodulatory activity: mitogenic stimulation of human tumor-infiltrating lymphocytes.

A serum-free supernatant from an epidermal carcinoma cell line has previously been shown to contain mitogenic activity for human tumor infiltrating lymphocytes in culture [1]. From this conditioned medium we have now purified to homogeneity, as determined by SDS-PAGE analysis, a ca. 45 kDa protein which stimulates [3H]thymidine incorporation into the DNA of these human T-lymphocytes. Amino acid composition data and immunoreactivity of the purified protein as well as sequence analyses of 7 tryptic fragments obtained therefrom suggest a strong similarity with human monocyte/neutrophil elastase inhibitor, which is a member of the serine protease inhibitor (serpin) superfamily. We have previously identified and purified from the same conditioned medium a 36 kDa protein with myeloid immunomodulatory activity [2]. Taken together, these two reports support the role of tumor-derived soluble factors in tumor immunosurveillance.

Amino Acid Sequence↗
PubMed1995

Pilot-scale harvest of recombinant yeast employing microfiltration: a case study.

In order to develop a cost-effective recovery process for an intracellular product, crossflow microfiltration was studied for the harvest of a recombinant yeast under severe time constraint. It was required to process yeast broth in a short period of time to minimize the risk for product degradation. Preliminary microfiltration studies employing flat sheet membranes showed high throughout with initial fluxes on the order of water fluxes (> 1000 LMH, regime I, < 2 min), followed by a rapid decay towards a low pseudo-steady state flux (20 LMH, regime II, > 2 min). Exploitation of these high fluxes and control of their eventual decline were crucial in establishing a rapid crossflow filtration process. The effect of several parameters, such as initial cell concentration, shear rate, transmembrane pressure, membrane pore size and medium composition on filtration performance were investigated to better understand the flux decline mechanisms. We found that the major contributor to flux decay was reversible fouling by the cake formation on the membrane surface. Within the operating boundaries of our microfiltration system, large-pore membrane (0.65 micron) was much more desirable for harvesting our yeast (10 microns size) without cell leakage than smaller pore ones (0.22 micron and 0.45 micron). Among adjustable operating parameters, feed flow rate (i.e., shear rate) exerted significant impact on average flux, whereas manipulation of transmembrane pressure afforded little improvement. Although initial cell concentration affected adversely the permeation rates, growth medium components, especially soy-peptone, was deemed pivotal in determining the characteristics of cell cake, thus controlling yeast microfiltration.

Culture Media↗
PubMed1995

Interaction of herpes simplex virus 1 origin-binding protein with DNA polymerase alpha.

The herpes simplex virus 1 (HSV-1) genome encodes seven polypeptides that are required for its replication. These include a heterodimeric DNA polymerase, a single-strand-DNA-binding protein, a heterotrimeric helicase/primase, and a protein (UL9 protein) that binds specifically to an HSV-1 origin of replication (oris). We demonstrate here that UL9 protein interacts specifically with the 180-kDa catalytic subunit of the cellular DNA polymerase alpha-primase. This interaction can be detected by immunoprecipitation with antibodies directed against either of these proteins, by gel mobility shift of an oris-UL9 protein complex, and by stimulation of DNA polymerase activity by the UL9 protein. These findings suggest that enzymes required for cellular DNA replication also participate in HSV-1 DNA replication.

Animals↗
PubMed1995

Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2.

Cytochrome P450 1A2 (CYP1A2) is a constitutively expressed hepatic enzyme that is highly conserved among mammals. This protein is primarily involved in oxidative metabolism of xenobiotics and is capable of metabolically activating numerous procarcinogens including aflatoxin B1, arylamines, heterocyclic amine food mutagens, and polycylic aromatic hydrocarbons. Expression of CYP1A2 is induced after exposure to certain aromatic hydrocarbons (i.e., 2,3,7,8-tetrachlorodibenzo-p-dioxin). Direct evidence for a role of CYP1A2 in any physiological or developmental pathway has not been documented. We now demonstrate that mice homozygous for a targeted mutation in the Cyp1a-2 gene are nonviable. Lethality occurs shortly after birth with symptoms of severe respiratory distress. Mutant neonates display impaired respiratory function associated with histological signs of lung immaturity, lack of air in alveoli at birth, and changes in expression of surfactant apoprotein in alveolar type II cells. The penetrance of the phenotype is not complete (19 mutants survived to adulthood out of 599 mice). Surviving animals, although lacking expression of CYP1A2, appear to be normal and are able to reproduce. These findings establish that CYP1A2 is critical for neonatal survival by influencing the physiology of respiration in neonates, thus offering etiological insights for neonatal respiratory distress syndrome.

Animals↗
PubMed1995

Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor.

The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr-/-) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr-/- mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct fibrosis Ahr-/- mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds. Thus, the AHR plays an important role in the development of the liver and the immune system.

Animals↗
PubMed1995

In vivo assembly of rhodopsin from expressed polypeptide fragments.

Rhodopsin folding and assembly were investigated by expression of five bovine opsin gene fragments separated at points corresponding to proteolytic cleavage sites in the second or third cytoplasmic regions. The CH(1-146) and CH(147-348) gene fragments encode amino acids 1-146 and 147-348 of opsin, while the TH(1-240) and TH(241-348) gene fragments encode amino acids 1-240 and 241-348, respectively. Another gene fragment, CT(147-240), encodes amino acids 147-240. All five opsin polypeptide fragments were stably produced upon expression of the corresponding gene fragments in COS-1 cells. The singly expressed polypeptide fragments failed to form a chromophore with 11-cis-retinal, whereas coexpression of two or three complementary fragments [CH(1-146) + CH(147-348), TH(1-240) + TH(241-348), or CH(1-146) + CT(147-240) + TH(241-348)] formed pigments with spectral properties similar to wild-type rhodopsin. The NH2-terminal polypeptide in these rhodopsins showed a glycosylation pattern characteristic of wild-type COS-1 cell rhodopsin and was noncovalently associated with its complementary fragment(s). Further, the CH(1-146) + CH(147-348) rhodopsin showed substantial light-dependent activation of transducin. We conclude that the functional assembly of rhodopsin is mediated by the association of at least three protein-folding domains.

Animals↗
PubMed1995

Suppression of cytochrome P450 (Cyp1a-1) induction in mouse hepatoma Hepa-1C1C7 cells by methoxsalen.

Cultured mouse hepatoma cell line Hepa-1c1c7 cells were treated with methoxsalen to assess the role of methoxsalen in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as indicated by analysis of 7-ethoxyresorufin O-deethylation (EROD) activity and P4501A1 protein. When methoxsalen and TCDD were both added to cultures, TCDD-inducible EROD activity was greatly suppressed by methoxsalen in a dose-dependent manner. We find that treatment of Hepa-1c1c7 cells with methoxsalen inhibited CYP1A1 mRNA induction by TCDD as well as the concomitant increase P4501A1 protein. Formation of DNA-protein complexes between the dioxin receptor and its DRE target was inhibited by methoxsalen, as determined by gel mobility shift assays using oligonucleotides corresponding to DRE 3 of the Cyp1a-1 gene. These results suggest that the inhibitory action of methoxsalen on TCDD induction of the Cyp1a-1 gene expression in Hepa-1c1c7 cells might be antagonism of the DNA binding potential of nuclear dioxin receptor.

Animals↗
PubMed1995

Upright postures and isoproterenol infusion for provocation of neurocardiogenic syncope: a comparison of standing and head-up tilting.

Head-up tilt testing has proved to be useful in provocation of neurocardiogenic syncope. The purpose of this study was to examine whether simply assuming an upright posture by standing can be an alternative to the head-up tilt testing for diagnosis of neurocardiogenic syncope. Eighty-four patients with recurrent unexplained syncope and 22 normal volunteers were recruited into the study. Forty-seven patients with syncope and all normal volunteers received the standing test. Thirty-seven of the patients with syncope received head-up tilt testing (90 degrees). All subjects lay down for 5 minutes and then assumed an upright posture until syncope or presyncope occurred or until a maximum of 10 minutes was reached in each stage of the test. The tests included four stages: baseline and infusion of 1, 2, or 3 micrograms/min isoproterenol in each of the successive stages. Five subjects could not tolerate the procedure, and further testing was terminated. Overall, the standing test was positive in 83% of the patients with syncope, and its specificity was 74%. The head-up tilt testing was positive in 75% of the patients with syncope. The duration of assuming an upright posture before occurrence of syncope or presyncope was significantly longer in the syncope-tilting group in the third stage (p < 0.01) and the fourth stage (p < 0.05) compared with the syncope-standing group. However, the curves of the time course for cumulative positive rates were not significantly different (p = 0.0739) in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a primary pungent and irritating principle present in chilies and red peppers which are widely used as spices. Because of its selective effects on the functions of a defined subpopulation of sensory neurons, capsaicin is currently used as a versatile tool for the study of pain mechanisms and also for pharmacotherapy to treat several pain disorders. Considering the frequent consumption of capsaicin as a food additive and its current medicinal use, correct assessment of hazardous effects of this compound is important. Mutagenic and carcinogenic activities of capsaicin and chili extracts have been studied, but results are conflicting. Mammalian metabolism of capsaicin has been also reported. Capsaicin appears to interact with xenobiotic metabolizing enzymes, particularly microsomal cytochrome P450-dependent monooxygenases which are involved in activation as well as detoxification of various chemical carcinogens and mutagens. Recent studies have shown that hepatic cytochrome P450 2E1 catalyzes the conversion of capsaicin to reactive species such as the phenoxy radical intermediate capable of covalently binding to the active site of the enzyme as well as tissue macromolecules. While covalent modification of protein and nucleic acids leads to toxicity including necrosis, mutagenesis, and carcinogenesis, suicidal inhibition of microsomal cytochrome P450 may prohibit further activation of capsaicin and also of other toxic xenobiotics. Results from recent studies indicate that capsaicin possesses the chemoprotective activity against some chemical carcinogens and mutagens.

Animals↗
PubMed1995

A reduced dose approach to hepatitis B vaccination for low-risk newborns and preschool children.

The effectiveness of a 2.5 micrograms dose of the hepatitis B vaccine (B-Hepavac II) was compared with that of 5 micrograms in 587 low-risk neonates and 777 preschool children of age 3-8 years. The vaccines were administered at months 0, 1 and 3, with postvaccination serology tested at months 4 and 12. The seroconversion rates of the 2.5 microgram recipients (newborn: 93.5%; preschool children: 97.4%) are comparable with the 5 micrograms group (newborn: 95.7%; preschool children: 98.7%). The seroconversion rates of the newborns are, however, significantly lower in the 2.5 micrograms group if positive response is taken as a titre > 10 IU l-1, instead of > 0 IU l-1. The older children, on the other hand, achieved a higher seroconversion rate and geometric mean titre (GMT) when compared with the newborns. irrespective of the dose received.

Child, Preschool↗
PubMed1995

Practice of drug abuse among inmates of a drug rehabilitation centre in Hong Kong.

Sharing of contaminated injection equipment accounts for the rapid spread of the human immunodeficiency virus (HIV) among injecting drug users (IDUs). The profile of drug addiction practice among inmates of the Shek Kwu Chau Drug Rehabilitation Centre in Hong Kong was studied. Registers on all the new admissions to the Centre during a two-year period between 1990 and 1992 were reviewed. Of the 3129 drug users studied, 68.7% were aged between 21 and 40; 84.8% were IDUs and heroin was the commonest drug of addition. Nearly 70% of the IDUs had never shared injection equipment with others. There were significantly more young addicts (< or = 30 years old) who had shared needles compared with the older ones (31.2% vs 26.8%, P < 0.05). Those with addiction time > 6 months were more likely to have shared needles than the new ones. Only 19% of the drug users accepted HIV testing at their first admission. Factors speculated for the low needle-sharing rates among IDUs in Hong Kong and the low HIV prevalence in the IDU population are discussed. It is of utmost importance to monitor continuously such a high-risk behaviour pattern so as to design appropriate intervention strategies to stop the transmission of HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Vasodilatory responses of isolated arteries of cirrhotic rats.

1. There is currently considerable interest in the role of locally produced vasodilators such as nitric oxide and adenosine in the pathogenesis of the peripheral vasodilatation of cirrhosis. However, the signal transduction pathways involving guanylate cyclase and adenylate cyclase have not been clearly delineated in the isolated blood vessel. 2. We therefore aimed to examine the in vitro vasorelaxant effects of the endothelium-dependent dilator bethanechol, the endothelium-independent dilator sodium nitroprusside and adenosine, as drugs that work via activation of guanylate and adenylate cyclases, in isolated aortic and superior mesenteric arterial rings from cirrhotic and control rats. 3. Cirrhosis was induced by chronic bile duct ligation and section of 24-28 days' duration, while controls underwent sham operation. The vessels were precontracted with the alpha 1-adrenoceptor agonist phenylephrine, then relaxed by incremental doses of the three drugs. 4. Marked attenuation of vasoconstriction induced by phenylephrine in isolated aortic and mesenteric arterial rings from cirrhotic rats compared with the control vessels was observed. 5. There were no significant differences in relaxation between the cirrhotic and control vessels to the three drugs. We conclude that in vitro vasodilatory responses mediated through signal transduction pathways involving guanylate cyclase and adenylate cyclase remain unchanged in a rat model of biliary cirrhosis.

Adenosine↗
PubMed1995

Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators.

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in rodents, we disrupted the ligand-binding domain of the alpha isoform of mouse PPAR (mPPAR alpha) by homologous recombination. Mice homozygous for the mutation lack expression of mPPAR alpha protein and yet are viable and fertile and exhibit no detectable gross phenotypic defects. Remarkably, these animals do not display the peroxisome proliferator pleiotropic response when challenged with the classical peroxisome proliferators, clofibrate and Wy-14,643. Following exposure to these chemicals, hepatomegaly, peroxisome proliferation, and transcriptional-activation of target genes were not observed. These results clearly demonstrate that mPPAR alpha is the major isoform required for mediating the pleiotropic response resulting from the actions of peroxisome proliferators. mPPAR alpha-deficient animals should prove useful to further investigate the role of this receptor in hepatocarcinogenesis, fatty acid metabolism, and cell cycle regulation.

Animals↗
PubMed1995

Effects of Ganoderma lucidum and krestin on cellular immunocompetence in gamma-ray-irradiated mice.

The effects of Ganoderma lucidum (Gl) and Krestin (PSK) extracts on cellular immunocompetence, leukocyte counts and differential count in gamma-irradiated mice were investigated in this study. ICR strain male mice were used and randomly divided into five groups. Group A is normal control. Group B, the experimental control, was treated with Gl. Group C, the radiation treatment control, was treated with whole body exposure to 4 Gy gamma-irradiation (RT). Group D was treated with RT and Gl. Group E was treated with RT and PSK. The dosage of Gl was 400 mg/day/kg body weight and PSK was 500 mg/day/kg body weight. After irradiation, six mice from each group were sacrificed on day 7 and the other six on day 28. Cellular immunocompetence was measured by means of 3H-thymidine incorporation with splenic cells stimulated through mitogens such as PHA, Con A and LPS. The results revealed that relative splenic weight in Groups D and E were higher than group C on day 28 after gamma-irradiation, Group D was the highest in all the experimental groups. Leukocyte counts were decreased significantly in Groups D and E on day 7, the former was a little higher than the latter. Gl administration showed an increase in the leukocyte count in Group D on day 28. The blastogenic response of splenocytes to PHA and Con A in groups D and E were higher than in Group C on days 7 and 28. We suggested that Gl and PSK were effective in enhancing the recovery of cellular immunocompetence from gamma-ray irradiation.

Animals↗
PubMed1995

Radiation-induced decrease in nitric oxide synthase--containing nerves in the rat penis.

PURPOSE: Evaluate effect of prostatic irradiation on erectile function. MATERIALS AND METHODS: Forty-seven male adult rats were divided into three groups according to a single radiation dose to the prostate: control (no irradiation) (n = 15), 1,000 cGy (n = 15), and 2,000 cGy (n = 17). Five months after irradiation, rats underwent evaluation of penile vascularity and of erectile response to central and peripheral stimulation. After the study a proximal-shaft penile segment was obtained for staining. RESULTS: Histologic evaluation demonstrated that, with increasing radiation, the number of nitric oxide synthase-containing nerve fibers per penile segment decreased significantly: control, 225.6 +/- 9.7; 1,000 cGy, 156.3 +/- 12.0; 2,000 cGy, 85.8 +/- 10.1 (standard error of the mean). Maximal intracavernous pressure induced with electrostimulation decreased significantly with increasing radiation dose. After injection of papaverine, maximal intracavernous pressure was significantly decreased in only the 2,000-cGy group. CONCLUSION: A dose of 2,000 cGy over the prostatic bed induces erectile dysfunction by causing defects in the vascular supply of the erectile tissue and in the nerves and smooth muscle.

Amino Acid Oxidoreductases↗