Biomedical subjects

S Yan

Publications and source records attributed to S Yan.

At least 19 recordsLinked to original sources

PubMed1995

Met-enkephalin-like immunoreactivity in microdialysates from nucleus tractus solitarii in piglets during normoxia and hypoxia.

Met-enkephalin-like immunoreactivity in microdialysates from the respiratory-related nucleus tractus solitarii was determined simultaneously with ventilatory responses in seven, spontaneously breathing, developing swine under conditions of normoxia, hypoxia and recovery from hypoxia for 30 min each. Assayed levels of Met-enkephalin-like immunoreactivity in normoxia were 0.89 +/- 0.23 pg/microliters. These levels increased to 203.6 +/- 32.2% and 283.1 +/- 55.8% of control during hypoxia and recovery, respectively. Hyperventilation during hypoxia was not sustained, comprising brief stimulation followed by return to near-control level. Taken together, these results provide further evidence that opioid release may contribute to the suppression of ventilation in hypoxia during development.

Animals↗

PubMed1995

Transforming growth factor beta-induced activation of cyclin E-cdk2 kinase and down-regulation of p27Kip1 in C3H 10T1/2 mouse fibroblasts.

Transforming growth factor (TGF-beta)-stimulated induction of DNA synthesis is preceded by the activation of cyclin E/cyclin-dependent kinase (cdk)2 kinase in late G1 in C3H 10T1/2 mouse fibroblasts. TGF-beta has no effect on the steady-state level of cdk4, while having only a modest inductive effect on cyclin D1 expression. TGF-beta stimulation does, however, lead to the striking down-regulation of p27Kip1 expression during G1 in a manner consistent with the timing of cyclin E-cdk2 activation. Coimmunoprecipitation analysis reveals that the amount of p27Kip1 in complexes with the cdk2 catalytic subunit is drastically reduced at the time in late G1 when cyclin E-cdk2 activity is maximal. These data indicate that cyclin E-cdk2 is inhibited by p27Kip1 in the growth-arrested state and that TGF-beta relieves this inhibition by down-regulating the steady-state level of the p27Kip1 inhibitor protein, thus reducing the level of inhibitor present in complexes with cdk2.

Animals↗

PubMed1995

Malignant and normal T cells show random use of T-cell receptor alpha chain variable regions in patients with cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature T lymphocytes, most of which express alpha/beta type T-cell receptors (TCRs). The cause of CTCL is unknown, but hypotheses postulating chronic stimulation of TCRs by superantigen or by a leukemogenic virus have been proposed. Either mechanism might produce bias in the TCR variable (V) region types used by the malignant cells. To determine if TCR alpha use is restricted in CTCL, we used reverse transcription and the polymerase chain reaction to determine V alpha and V beta usage by malignant cells purified from the peripheral blood of leukemic patients with CTCL. Usage of alpha chain V region segments appeared totally random; malignant lymphocytes isolated from each of six patients used different V alpha regions. As has been previously reported, no bias was found in beta chain V region usage either. In addition to productive (in frame) TCR V region mRNAs in malignant cells from each patient, we detected non-productive (out of frame) beta chain transcripts in these cells in two of six patients, and non-productive alpha chain transcripts in five of six. Residual normal peripheral blood lymphocytes from these patients showed a random, polyclonal or oligoclonal pattern of V region usage. We conclude that there is no bias in V region usage in CTCL, making it unlikely that interactions between superantigen or virus and the TCR V regions play a role in the pathogenesis of CTCL.

Aged↗

PubMed1995

Microdialyzed adenosine in nucleus tractus solitarii and ventilatory response to hypoxia in piglets.

Levels of adenosine, inosine, and hypoxanthine from the interstitial space at the nucleus tractus solitarii were measured by microdialysis in eight 20- to 25-day-old anesthetized spontaneously breathing piglets. Microdialyzed samples were collected every 30 min for 2 h after the insertion of the probe to ensure stability of purine levels and then during 30 min each of normoxia, hypoxia (10% O2-90% N2), and normoxia. The purines were separated by high-pressure liquid chromatography with ultraviolet detection and quantified at 254-nm wavelength. Tidal volume, breathing frequency, minute ventilation, mean arterial blood pressure, pH, and gas tensions were measured. Compared with control, adenosine levels during hypoxia increased by 40.7 +/- 5.5% and then tended to decline during the recovery from hypoxia, but the levels remained higher than in control. Ventilatory measures exhibited a modest biphasic pattern during hypoxia and resumed control values by 10 min after the removal of the hypoxia. The increased adenosine release during hypoxia provides additional evidence for the possible participation of adenosine in the central suppression of breathing during hypoxia.

Adenosine↗

PubMed1995

Effects of fatigue, fiber length, and aminophylline on human diaphragm contractility.

The clinical relevance of methylxanthines as therapeutic agents for improving diaphragmatic contractility is controversial. In a double-blind, placebo-controlled trial, we investigated the effect of aminophylline on the contractility of fresh and fatigued human diaphragm at different lung volumes, and therefore as a function of fiber length. The diaphragmatic contractility of normal subjects was assessed by measurements of transdiaphragmatic pressure changes (Pdi,T) in response to single, bilateral, supramaximal phrenic-nerve shocks during relaxation from total lung capacity (TLC) to functional residual capacity (FRC). Fatigue was induced by resistive breathing. Therapeutic levels of theophylline were reached in all subjects. Under fresh (i.e., nonfatigue) conditions, aminophylline significantly increased Pdi,T at lung volumes above 75% of the inspiratory capacity (IC). Fatigue in the absence of aminophylline caused a disproportionately greater reduction of Pdi,T at high than at low lung volume (J. Appl. Physiol. 1992; 72:1064), which was rapidly reversible with rest. With aminophylline, the disproportionate decrease in diaphragmatic contractility at short fiber lengths was not observed. Aminophylline potentiates diaphragmatic contractility to a proportionately greater extent at short than at long fiber lengths, under both fresh and fatigued conditions. We explain these findings by known effects of muscle shortening, fatigue, and methylxanthines on excitation-contraction coupling mechanisms.

Adult↗

PubMed1995

Abrupt reduction of c-myc expression by antisense RNA inducing terminal differentiation and apoptosis of a human esophageal cancer cell line.

A human esophageal cancer cell line (EC8712) expressing high-level Myc protein was infected with recombinant retroviral particles (pA-BD9) at a multiplicity of infection (MOI) 1:1. This viral particle contains a neomycin-resistant gene and a 1.53-kb antisense RNA spanning the 2nd exon and its flanking sequences of the human c-myc oncogene. The G418-resistant EC8712 clones showed an 86% inhibition of growth rate and morphological changes characteristic of terminal differentiation and apoptosis. A decrease of about 80% of Myc protein was also observed in these infected cells by ABC-ELISA assay. 12-24 h after the infection of EC8712 cells with pA-BD9 at a high viral particle concentration (MOI = 1:10), the integration of the extrinsic 1.53-kb antisense c-myc fragment into the cancer cell genome was evidenced by the Southern blot analysis. Northern blot analyses showed the expression of this antisense fragment and a decrease of the intrinsic c-myc expression by 74% in comparison with that of the parental EC8712 cells. Heterotransplants of the infected EC8712 cells into the nude mice revealed a substantial decrease in tumorigenicity and morphological changes characteristic of terminal differentiation and apoptosis. Primary monolayer cell cultures of normal epithelia derived from the fetal and adult esophagus mucosa were set as controls. No noticeable increase in c-myc expression was found in these cultures. Infection of these cells with the same recombinant viral particles neither affected the growth rate of the cells nor their normal morphology. Our experiments indicate that the drastic decrease of the over-expressed Myc protein in cancer cells may also be an entrance to one of many pathways leading to the terminal differentiation and programmed cell death.

Animals↗

PubMed1995

[Effects of nitroglycerin, prostaglandin E1, trimetaphan and nicardipine on systemic vascular resistance, pulmonary vascular resistance and pulmonary-systemic vascular resistance ratio in dogs].

Effects of the experimentally induced hypotension with 4 vasodilators; nitroglycerin (TNG), prostaglandin E1 (PGE1), trimetaphan (TMP) and nicardipine (NCP) on systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and pulmonary-systemic vascular resistance ratio (PVR/SVR ratio) were studied in dogs. The SVR values were significantly reduced by TNG, PGE1 and NCP, and not affected by TMP. The PVR values were significantly reduced by TNG and PGE1, and not affected by TMP and NCP. The PVR/SVR ratio values were significantly reduced by TNG, and significantly increased by NCP, and not affected by PGE1 and TMP. We concluded that TNG reduced PVR and SVR but it affected PVR more; PGE1 reduced PVR and SVR equivalently; TMP did not affect PVR and SVR remarkably; NCP reduced SVR but did not affect PVR.

Alprostadil↗

PubMed1994

Persistent acylation of high-molecular-weight penicillin-binding proteins by penicillin induces the postantibiotic effect in Streptococcus pyogenes.

Penicillin at 10X MIC induced a postantibiotic effect (PAE) of 2.1 h in Streptococcus pyogenes. Progressive increases in the densities of penicillin-binding proteins (PBPs) 1-3 of the bacterium were detected at 30, 60, and 90 min during the postantibiotic phase. The increase in colony-forming units during this phase paralleled the kinetics of incorporation of lysine into proteins, suggesting that growth was triggered by de novo synthesis of PBPs. The question was raised as to whether the progressive increases in densities of PBPs were due to the restoration of preexisting PBPs or to synthesis of new PBPs. With 10X MIC of clindamycin to inhibit PBP synthesis during the postantibiotic phase, the temporal increase in densities of PBPs 1-3 were totally inhibited. These results suggest that the PAE of penicillin in S. pyogenes is caused by irreversible binding of penicillin to PBPs 1-3 and represents the time necessary for synthesis of new PBPs required for normal growth.

Acylation↗

PubMed1993

Effect of diaphragmatic fatigue on control of respiratory muscles and ventilation during CO2 rebreathing.

We studied the influence of diaphragmatic fatigue on the control of ventilation and respiratory muscle contribution to pressure swings in six normal seated subjects. CO2 was rebreathed before and after diaphragmatic fatigue induced by breathing against an inspiratory resistance requiring 60% maximal transdiaphragmatic pressure with each breath until exhaustion. After diaphragmatic fatigue for a given level of end-tidal PCO2, we found that tidal volume, breathing frequency, minute ventilation, duty cycle, and mean inspiratory flow did not change; esophageal pressure swings were the same, but gastric and transdiaphragmatic pressure swings were decreased; and the slope of the transpulmonary pressure-gastric pressure relationship determined at zero flow points at end expiration and end inspiration was increased. End-expiratory transpulmonary pressure progressively decreased and end-expiratory gastric pressure progressively increased with increasing end-tidal PCO2 by the same magnitude before and after diaphragmatic fatigue. We conclude that diaphragmatic fatigue induces proportionately greater contributions of inspiratory rib cage muscles than of the diaphragm, which results in the preservation of ventilatory response to CO2 despite impaired diaphragmatic contractility.

Adult↗

PubMed1993

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2.

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.

Adult↗

PubMed1993

3-Isobutyl-1-methylxanthine inhibits sustained calcium current independently of cyclic AMP in neuronal and endocrine cells.

The effect of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) on the voltage-dependent calcium current was studied in the clonal pituitary cell line GH3 by whole-cell patch-clamp techniques. It was found that IBMX reversibly inhibited the sustained calcium current (Ki, 1.25 mM), whereas there was no effect on the transient current. IBMX increased the inactivation rate of the sustained current without altering the voltage of activation. Vasoactive intestinal peptide, an agent known to increase cAMP, was without effect on the calcium current. The effect of IBMX was not altered by pretreating the cells with pertussis toxin or by including either cAMP or protein kinase inhibitor in the intracellular solution. The order of potency for several xanthine derivatives was IBMX > theophylline > caffeine > xanthine. The effect of IBMX on calcium current was also observed in three additional neuronal and endocrine cell lines (PC12, SY5Y, and RINm5f). These results indicate that IBMX inhibits sustained voltage-dependent calcium current by a mechanism independent of alterations in cAMP levels.

1-Methyl-3-isobutylxanthine↗

PubMed1993

In vitro oocyte maturation in the zebra fish, Brachydanio rerio, and the fertilization and development of the mature egg.

The in vitro maturation process of zebra fish oocytes was investigated. When incubated with medium EM-199 containing 0.5 microgram/ml of 17 alpha-hydroxyprogesterone in an incubator with 80% O, 25 degrees C, the germinal vesicles of the oocytes in stage IV migrated from middle between the center and the periphery to the periphery in 40 min, and the oocytes went into stage V 30 min later, undergoing germinal vesicle breakdown (GVBD) with a GVBD% of 59%. Two hours were needed for such oocytes to complete their final maturation. The mature eggs cannot come off the follicle layer surrounding them naturally (ovulation). By removing the follicle and adding active sperm for insemination, we can cause the mature eggs to become fertilized. The chorion elevated and blastoderm formed on the animal pole. The cleavage and development of the fertilized eggs followed are the same as naturally matured fertilized eggs. Using blastula as the criterion for a successful fertilization of the in vitro maturated egg, the fertilization rate is 78%. This is the first report on the successful oocyte final maturation in vitro in zebra fish. The establishment of an oocyte in vitro maturation technique has given grounds for the further investigation on the transfer of foreign genes in the germinal vesicles of the oocytes.

17-alpha-Hydroxyprogesterone↗

PubMed1993

[A study on the transcriptional expression of oncogenes in human primary brain tumors].

The c-myc, L-myc, N-myc, Ha-ras, c-fos, and v-erbB oncogenes were used as probes to detect the total RNA of 5 cases of normal human brain tissues and 29 cases of brain tumor tissues by RNA dot hybridization analysis. The results showed that the increasing expressions of cerbB and c-fos were the highest, being 88.2% and 82.4%, respectively, the next was c-myc with an increased expression of 46.1%; the increasing expressions of L-myc (29.3%) and N-myc (31.6%) were observed in a few samples only. There was no significant difference of Ha-ras gene expression between normal brain and brain tumor. In addition, we observed the increasing expression of more than one oncogene in one sample. These results suggest that c-erbB and c-fos oncogenes may play an important role in the pathogenesis of human primary brain tumors, and that multiple genetic changes are implicated in genesis of human brain tumors.

Brain Neoplasms↗

PubMed1992

Effect of fatigue on diaphragmatic function at different lung volumes.

The transdiaphragmatic pressure twitches (PdiT) in response to single maximal shocks delivered bilaterally to the phrenic nerves were recorded as a function of lung volume when the diaphragm was fresh and when fatigued. All relationships were linear and negatively sloped (all r greater than 0.85). From these relationships PdiT was found to decrease with fatigue more rapidly and to recover more quickly at high than at low lung volumes. Complete recovery of PdiT at all lung volumes was greater than 1 h. Contraction and relaxation rate constants of PdiT did not change significantly with fatigue. We conclude that fatigue affects diaphragm contractility more at high than at low lung volumes and that changes in diaphragm contractility are best reflected in the measurement of PdiT as a function of lung volume.

Adult↗

PubMed1992

Evaluation of human diaphragm contractility using mouth pressure twitches.

Mouth (PmT), esophageal (PesT), and transdiaphragmatic pressure twitches (PdiT) in response to single supramaximal bilateral phrenic nerve shocks were recorded during relaxation between total lung capacity (TLC) and functional residual capacity (FRC) in five normal volunteers. The PmT versus PesT or PmT versus PdiT relationships, which were linearly correlated (all r greater than 0.76), were not affected by diaphragm fatigue and were reproducible on repeated determinations over a period exceeding 1 yr. The PmT versus lung volume relationship was also linear (all r greater than 0.72) and reproducible, and its changes following diaphragm fatigue reliably reflected the changes in diaphragm contractility. We conclude that PmT is a reliable measure of diaphragm pressure-generating capacity in normal individuals and has the potential of providing similar information in patients.

Adult↗

PubMed1992

Mitochondrial DNA content and mitochondrial gene transcriptional activities in the early development of loach and goldfish.

The mitochondrial DNA (mtDNA) content of the mature eggs and embryos of loach and goldfish at early developmental stages were detected by means of dot hybridization. The transcription of mitochondrial cytochrome oxidase subunit I and II (COI and COII) genes during their early development was also detected by Northern hybridization. The experimental results showed that the mtDNA content of the mature egg as well as that of the embryos during the period from fertilized egg up to hatching stage in both fishes is maintained at a constant level, giving an average value of 7.40 x 107 molecules or 1.33 ng for every embryo in loach and an average value of 1.87 x 10(8) molecules or 3.31 ng for every embryo in goldfish. In both fish embryos, the COI and COII transcripts declined gradually after fertilization until late-blastula stage and then increased in early gastrula stage. This indicated that the transcription of mitochondrial genomes of these two freshwater fishes, which belong to different families, might be activated at the beginning of gastrulation. The steady-state amounts of mitochondrial messenger transcripts existing in the embryos during the early development in both fishes seemed to be regulated by both their half-lives and the transcriptional level of the mitochondrial genomes. The results showed that the transcription of the mitochondrial genome in the early developmental process in loach and goldfish was not regulated by a gene dosage mechanism.

Animals↗

PubMed1991

Contractile properties of the human diaphragm during chronic hyperinflation.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS: In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS: At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS: The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.

Aged↗

PubMed1991

[A case-control study of ulcerative colitis].

In order to evaluate the epidemiological characteristics of ulcerative colitis, we conducted a matched case-control study of ulcerative colitis. Fifty patients with ulcerative colitis diagnosed at three hospitals in Kyoto, Osaka and Hyogo Prefectures in Japan during 1984 and 1987 were interviewed about their habitual and pre-illness diets, personal habits, past histories and family histories. The results were compared to those for fifty healthy controls who were matched for sex and age (+/- 2 years) and participated in health-screening examinations in Kyoto or Osaka during the same period. Frequent intake of rice (4 or more bowls a day), bread (3 or more times a week), and green tea (7 or more cups a day) significantly increased the relative risk of ulcerative colitis. However, a past history of appendectomy was negatively correlated with the disease. There were no relationships between ulcerative colitis and consumption of animal foods and tobacco.

Adolescent↗