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Biomedical subjects

C Ng

Publications and source records attributed to C Ng.

At least 19 recordsLinked to original sources
PubMed2000

Global adaptations resulting from high population densities in Escherichia coli cultures.

The scope of population density effects was investigated in steady-state continuous cultures of Escherichia coli in the absence of complications caused by transient environmental conditions and growth rates. Four distinct bacterial properties reflecting major regulatory and physiological circuits were analyzed. The metabolome profile of bacteria growing at high density contained major differences from low-density cultures. The 10-fold-elevated level of trehalose at higher densities pointed to the increased role of the RpoS sigma factor, which controls trehalose synthesis genes as well as the general stress response. There was an eightfold difference in RpoS levels between bacteria grown at 10(8) and at 10(9) cells/ml. In contrast, the cellular content of the DNA binding protein H-NS, controlling many genes in concert with RpoS, was decreased by high density. Since H-NS and RpoS also influence porin gene expression, the influence of population density on the intricate regulation of outer membrane composition was also investigated. High culture densities were found to strongly repress ompF porin transcription, with a sharp threshold at a density of 4.4 x 10(8) cells/ml, while increasing the proportion of OmpC in the outer membrane. The density-dependent regulation of ompF was maintained in rpoS or hns mutants and so was independent of these regulators. The consistently dramatic changes indicate that actively growing, high-density cultures are at least as differentiated from low-density cultures as are exponential- from stationary-phase bacteria.

Adaptation, Physiological↗
PubMed2000

Peak expiratory flow at increased barometric pressure: comparison of peak flow meters and volumetric spirometer.

Increasing numbers of patients are receiving hyperbaric oxygen therapy as an intensive care treatment, some of whom have pre-existing airway obstruction. Spirometers are the ideal instruments for measuring airway obstruction, but peak flow meters are useful and versatile devices. The behaviour of both types of device was therefore studied in a hyperbaric unit under conditions of increased pressure. It is important to have a non-electrical indicator of airway obstruction, to minimize the fire risk in the hyperoxic environment. The hypothesis was tested that, assuming that dynamic resistance is unchanged, both the Wright's standard and mini-peak flow meters would over-read peak expiratory flow (PEF) under increased pressure when compared with a volumetric spirometer, as the latter is unaffected by air density. It was postulated that a correction factor could be derived so that PEF meters could be used in this setting. Seven normal subjects performed volume-dependent spirometry to derive PEF, and manoeuvres using both standard and mini PEF meters at sea level, under hyperbaric conditions at 303, 253 and 152 kPa (3, 2.5 and 1.5 atmospheres respectively; 1 atmosphere absolute=101.08 kPa), and again at sea level. There was a progressive and significant decline in PEF with increasing pressure as measured by the spirometer (69.46+/-0.8% baseline at 303 kPa compared with 101 kPa), while the PEF meters showed a progressive increase in their readings (an increase of 7.86+/-1.69% at 303 kPa with the mini PEF meter). Using these data points, a correction factor was derived which allows appropriate values to be calculated from the Wright's meter readings under these conditions.

Adult↗
PubMed2000

Ca2+signalling in stomatal guard cells.

Ca(2+) is a ubiquitous second messenger in the signal transduction pathway(s) by which stomatal guard cells respond to external stimuli. Increases in guard-cell cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) have been observed in response to stimuli that cause both stomatal opening and closure. In addition, several important components of Ca(2+)-based signalling pathways have been identified in guard cells, including the cADP-ribose and phospholipase C/Ins(1, 4,5)P(3)-mediated Ca(2+)-mobilizing pathways. The central role of stimulus-induced increases in [Ca(2+)](cyt) in guard-cell signal transduction has been clearly demonstrated in experiments examining the effects of modulating increases in [Ca(2+)](cyt) on alterations in guard-cell turgor or the activity of ion channels that act as effectors in the guard-cell turgor response. In addition, the paradox that Ca(2+) is involved in the transduction of signals that result in opposite end responses (stomatal opening and closure) might be accounted for by the generation of stimulus-specific Ca(2+) signatures, such that increases in [Ca(2+)](cyt) exhibit unique spatial and temporal characteristics.

Adenosine Diphosphate Ribose↗
PubMed1999

Influenza vaccination: changes in exhaled nitric oxide levels and sputum cytology.

OBJECTIVE: Influenza vaccination is routinely recommended for patients with chronic lung disease, but has been reported to cause a small increase in airway reactivity. The use of simple, non-invasive methods of assessing changes in airway inflammation could potentially allow improved understanding of the cellular mechanisms underlying such changes. METHODOLOGY: We studied a group of 44 hospital workers before and after routine influenza vaccination, using spirometry, and exhaled nitric oxide (eNO) as a marker of pulmonary inflammation (Group A). In addition, methacholine challenge and sputum induction were also performed in a subgroup (subgroup B, n = 7) at baseline and at 7 days after vaccination. RESULTS: Spirometry did not change in either group. In Group A there was a small but significant rise in mean peak eNO from 47.32 +/- 4.5 (mean NO p.p.b. +/- SEM) to 53.2 +/- 4.9 between days 0 and 7 (P < 0.05). A non-significant rise in eNO was seen in subgroup B. In subgroup B, when the differential cell counts in induced sputum were compared between baseline and sampling 1 week later, there was a significant rise in the percentage of lymphocytes, from 3.9 (1.8-9.8: median %total (range)) to 11.9 (6.0-18.5, P < 0.02) and a non-significant increase in shed respiratory epithelial cells from 3.1 (0.6-5.8) to 13.0 (1-30.3, P=0.06). There was a corresponding significant fall in the percentage of macrophages. Methacholine challenge in subgroup B showed no change in reactivity in these normal subjects. CONCLUSION: Influenza vaccination causes a small increase in exhaled NO, and is accompanied by increased sputum lymphocytosis and respiratory epithelial shedding. An influx of inflammatory cells may help to explain the induction of increased airway reactivity that has been described in other studies.

Adult↗
PubMed1998

Delayed mid-ileal perforation secondary to acute-on-chronic ischaemia after a diagnostic colonoscopy.

Perforation occurring at a remote site of the bowel after diagnostic colonoscopy is rare. A 61-year-old man presenting with bloody diarrhoea underwent colonoscopy. A dynamic ileus developed in less than 1 day, and mid-ileal perforation occurred 7 days after the procedure. It is suggested that high air pressure during colonoscopy further compromised the reduced blood flow in the mid-ileum, which had underlying chronic ischaemia, leading to perforation. Our patient constitutes the first reported case of small-bowel perforation after colonoscopy due to pre-existent ileal ischaemia.

Acute Disease↗
PubMed1998

Induction of apoptosis and down-regulation of bcl-6 in mutu I cells treated with ethanolic extracts of the Chinese herbal supplement PC-SPES.

PC-SPES, an HPLC-standardized 8-herb dietary supplement prepared by proprietary extraction/mixing technologies, appears to have a number of health benefits when given to cancer patients. These include reduction of serum PSA (prostate specific antigen) in individuals diagnosed with advanced prostate carcinoma, and overall improvement of morbidity and immune status in terminal cancer cases. Since the expression of bcl-6 in T and B lymphocytes has been reported to be significantly down regulated by mitogens, we reason that the immune boosting effects of PC-SPES could involve the modulation of bcl-6 expression. Such a hypothesis was tested in the bcl-6 abundant Mutu I cells. Specifically, we investigated the effects of PC-SPES in regulating cell growth, induction of apoptosis, effecting changes in the retinoblastoma gene RB and the modulation of expression of the bcl-6. Herein we report that proliferation of Mutu I cells was inhibited by a 3-7 day incubation with ethanolic extracts of PC-SPES, with concurrent induction of apoptosis. In addition, a dose-dependent reduction of bcl-6 was observed, with no concomitant change in either the phosphorylated or the unphosphorylated forms of RB. These data raise the possibility that PC-SPES may enhance immune functions in vivo by down-regulating bcl-6 expression. Alternatively, decrease in bcl-6 could serve as a biomarker for testing the efficaciousness of PC-SPES in vivo.

Antineoplastic Agents, Phytogenic↗
PubMed1998

The role of endoscopic therapy in chronic pancreatitis-induced common bile duct strictures.

During endoscopic retrograde cholangiography, common bile duct strictures are encountered in up to 30% of patients with chronic pancreatitis. The indications for treatment of these strictures are discussed. A surgical biliodigestive anastomosis has always been the traditional treatment modality. Not all patients need treatment, however, and endoscopic biliary drainage is the treatment of choice for certain subgroups of patients.

Cholestasis↗
PubMed1997

Cellular changes and induction of apoptosis in human promyelocytic HL-60 cells infected with the agent of human granulocytic ehrlichiosis (HGE).

Human granulocytic ehrlichiosis (HGE) is an emerging and occasionally fatal human infectious disease whose pathogenesis is largely unknown. Goodman et al. (1) recently described the successful cultivation of the HGE infectious agent in human promyelocytic HL-60 leukemic cells. It was reported in the same study that infectivity invariably led to host cell death, although the mechanism by which HGE infection triggers cellular self-destruction is as yet undetermined. In this communication, we show that in vitro passage of HGE pathogen-infected blood elicits a significantly dysfunctional G1-to-S transition. Moreover, we provide evidence that the cytopathic properties of the HGE pathogen are attributed to its ability to induce apoptosis in host HL-60 cells. Determination of specific protein expression changes by Western blot analysis showed that HGE infection resulted in reduced expression of PCNA and pRB, both of which play a role in cell cycling. Moreover, the steady state level of bcl-2, which protects eukaryotic cells against apoptosis, is suppressed by exposure to the HGE agent. These results suggest that this pathogen HGE induces apoptosis in HL-60 cells by a mechanism involving the shut-off of multiple cell cycle and apoptosis regulatory events.

Apoptosis↗
PubMed1997

Pituitary dysfunction in recently post-menopausal women. Nottingham EPIC Study Group.

OBJECTIVE: Some recently post-menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo-pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post-menopausal women recruited to a bone loss prevention study. DESIGN: Prospective study of health volunteers. SETTING: Outpatient, teaching hospital in Nottingham UK. SUBJECTS: Forty-seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause. MAIN OUTCOME MEASURES: Response of the pituitary to formal stimulation tests and its relationship to bone mineral density. RESULTS: A significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups. CONCLUSIONS: Serum FSH concentrations are not invariably elevated in recently post-menopausal women and use of FSH as a determinant for postmenopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure of a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.

Bone Density↗
PubMed1997

Adrenal control of erectile function and nitric oxide synthase in the rat penis.

Penile erection is a nitric oxide (NO)-mediated process that has been shown to be androgen dependent in rats. Castration reduces the activity of the penile enzyme involved in NO synthesis, nitric oxide synthase (NOS). To determine whether adrenal androgens and/or corticosteroids contribute to this control, the following groups of Fischer 344 adult male rats (n = 5-7) were studied: 1) intact, 2) castrated, 3) adrenalectomized alone, 4) castrated/adrenalectomized, 5) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.) and hydrocortisone (12 mg/kg, s.c.), 6) castrated/adrenalectomized with dihydrotestosterone (1.2-cm SILASTIC-brand tubing pellet; Dow Corning, Midland, MI), 7) castrated/adrenalectomized with dehydroepiandrosterone (2-cm tubing), 8) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.), and 9) castrated/adrenalectomized with hydrocortisone (12 mg/kg, s.c.). After 1 week, EFS was applied, and the maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were recorded. The MIP/MAP ratio in the adrenalectomized group (0.37) was reduced to values found in the castrated group (0.40). The values in both groups were significantly less than those in intact controls (0.75). The most significant reduction in MIP/MAP was seen in the adrenalectomized/castrated group (0.16). Erectile response in animals submitted to adrenalectomy and castration was restored close to intact values with the administration of hydrocortisone and aldosterone (0.63). Similar results were obtained by the administration of either of the substances alone (0.56 and 0.67, respectively). Penile NOS activity assayed by the L-arginine/citrulline conversion was decreased by 55% in the castrated group compared with that in the intact group, but was not further reduced in the adrenalectomized/castrated or adrenalectomized groups. Penile neuronal NOS protein content, estimated by Western blot, was decreased only in the adrenalectomized/castrated animals (35%), and endothelial NOS content was not affected. These data suggest that the rat adrenal gland contributes to the maintenance of the erectile mechanism and may affect neuronal NOS content in the penis in the rat model. The possibility that hypotension may play a role in the erectile dysfunction observed in adrenalectomized rats cannot be discarded.

Adrenal Glands↗
PubMed1997

Effect of long-term passive smoking on erectile function and penile nitric oxide synthase in the rat.

PURPOSE: Given that smoking is a risk factor for erectile dysfunction, this study aimed to determine, in a rat model, whether long-term exposure to cigarette smoke impairs nitric oxide (NO)-dependent erectile function and reduces penile nitric oxide synthase (NOS), and if these changes are accompanied with effects on the systemic blood pressure. MATERIALS AND METHODS: Adult (5 month) and old (20 month) rats were exposed to daily passive smoking for 8 wks. Three days after the conclusion of exposure, half of the animals were submitted to electrical field stimulation (EFS) of the cavernosal nerve and the maximum intracavernosal pressure (MIP) and mean arterial pressure (MAP) were determined and expressed as mm. Hg. On the other half of the animals, NOS activity in the penile cytosol was measured by the arginine/citrulline assay, and neuronal NOS (nNOS) and endothelial NOS (eNOS) contents were estimated by western blot and densitometry. RESULTS: When compared to controls, the smoking rats had a higher MAP in both the adult (115 vs 162) and old (113 vs 140) rats, but surprisingly the MIP also increased, from 78 to 111 (adult rats) and from 59 to 83 (old rats). Smoking reduced penile NOS activity by 73% (adult rats), and 62% (old rats), and nNOS content by 43% and 50%, respectively. In contrast, eNOS was not affected. Nitrite release, in vitro, by cavernosa slices or in rat penile smooth muscle cells (RPSMC) was not inhibited by nicotine or cotinine. CONCLUSION: These results indicate that chronic smoking in the rat leads to age-independent moderate hypertension and considerable decreases in penile NOS activity and nNOS content, that are not reflected in a reduction of the erectile response to EFS or accompanied by a decrease in penile eNOS.

Age Factors↗
PubMed1996

Specific cleavage of recombinant protein tau3 between valine-220 and tyrosine-221 (val-309 and tyr-310 of tau4) by a double-stranded DNA-stimulated protease.

The protein tau was degraded to distinct products by a DNA-stimulated protease isolated from human leukemia HL-60 cell extracts. The enzyme partially purified by sequential chromatography on GTP-agarose, DEAE-cellulose, and TSK 3000 (0.6 X 60 mm) columns eluted as a 300-450 kDa protein which appeared as 60-90 kDa polypeptides on SDS-PAGE. Protease activity was stimulated by synthetic and natural DNAs and was most active at pH 8.5. Human recombinant tau3 was degraded by the DEAE-cellulose-eluted protease to a 26-kDa and several 14- to 16-kDa peptides. Degradation of tau was partially blocked by preincubation with tubulin, suggesting that the DNA-stimulated cleavage of tau occurred at the carboxyl-terminus, at or near the "tubulin-interactive" domains. The 26-kDa fragment was shown by amino acid sequencing to correspond to the N-terminus of tau whereas sequencing of the 16-kDa fragment yielded YKPVDLSKVT. These results show the existence of a DNA-stimulated protease capable of cleaving tau3 between valine-220 and tyrosine-221 (equivalent to valine 309 and tyrosine-310 of tau4).

Amino Acid Sequence↗
PubMed1996

Effects of IFN-beta and 1,25-dihydroxyvitamin D3 on cellular proliferation, induction of 2',5'-oligoadenylate (2-5A) synthetase and changes in immunoreactive pRB/p53 in human prostatic JCA-1 cells.

The combined antimitogenic effects of IFN-beta and 1,25-dihydroxyvitamin D3 (vit. D3) were investigated by treating the androgen-independent JCA-1 cells, established from the primary prostatic tumor site prior to anti-hormonal therapy, with IFN-beta (1000 IU/ml), vit. D3 (100 nM), and both agents. Cell growth, changes in overall RNA and protein contents, and cell cycle regulatory proteins pRB/p53 were determined. After a 24 h exposure, a significant reduction in cell proliferation was observed in all three conditions. IFN-beta, vit D3, and their combination elicited, respectively, a 1.7-, 1.6- and 2.5-fold increase in total RNA and a corresponding 1.4-, 1.2- and 1.7-fold increase in soluble proteins. The IFN-inducible 2-5A synthetase activity was elevated by 15-, 1.4- and 21-fold, respectively. No differences in cell cycle phase distribution were found between control and treated samples. However, a significant change in pRB and p53 expression was observed upon exposure to these agents. A progressive increase in total pRB was observed in untreated JCA-1 cells, with the 48 h culture showing a 1.9-fold increase over the 6 h culture. The ratio of phosphorylated to the nonphosphorylated forms of pRB, however, decreased from 3.00 at 6 h to 1.2 at 48 h. The overall pRB increase as well as the modified:unmodified protein ratio change were both markedly decreased when the cells were treated with IFN-beta, vit. D3, or their combination. With p53, a similar progressive increase was also observed in control cells, which was largely abolished by IFN-beta but only partially blocked by vit. D3. The combination of IFN-beta and vit. D3 gave results similar to samples receiving vit. D3 alone suggesting that the effects of IFN-beta, insofar as p53 modulation is concerned, is distal to the effects of vit. D3.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat.

Castration of adult male rats reduces by half the penile erectile response to electrical field stimulation (EFS) of the cavernosal nerve, and the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whether other strategies of androgen ablation or competition may act as stronger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left intact and were treated daily as follows: 1) intact, with the antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via silastic tubing, s.c.). Additional groups of intact rats received injections of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios between maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were determined. Castration reduced the MIP:MAP ratio and penile NOS activity. Androgen receptor blockade with flutamide induced a similar response in intact rats. When flutamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the values in castrated rats. Estradiol given to castrated rats and hypophysectomy or GnRHA treatment in intact rats diminished the erectile response below the level in castrated animals. In hypophysectomized rats, penile NOS activity fell below levels in castrated animals. contents of nNOS and eNOS were not significantly reduced by any treatment. These data suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of penile NOS activity and of other ancillary factors. However, only the complete blockade of residual androgen effects at the tissue level or a total androgen depletion can abolish the erectile response.

Androgen Antagonists↗
PubMed1996

Cavernosal nerve stimulation in the rat reverses castration-induced decrease in penile NOS activity.

Castration in the rat reduces both the erectile response and penile nitric oxide synthase (NOS) activity, and these effects are prevented by androgen administration. In this study we determined that the decrease of penile NOS in the castrated rat is due to NOS enzyme inhibition rather than to a reduction of its content and that this inhibition may be reversed. Adult rats were either castrated or left intact, and, after 1 wk, electrical field stimulation (EFS) was applied to the cavernosal nerve and the penises were excised either at the peak of erection or after detumescence. Penile NOS activity in the non-EFS castrates decreased by 70% as compared with the intact non-EFS-treated controls, but neuronal NOS content remained unaffected despite changes in regional distribution. NOS activity in the castrated penis was restored to normal values by EFS at the peak of stimulation, and then decreased on detumescence. This was in contrast to the intact controls in which EFS did not stimulate penile NOS activity. These data indicate that androgen depletion in the rat reduces penile NOS activity rather than NOS content and that this enzyme inhibition is reversed by cavernosal nerve stimulation.

Animals↗
PubMed1996

Autoregulation of myocardial glycogen concentration during intermittent hypoxia.

During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined hypoxic stimulus on the rat heart while varying its workload. In intact rats, hypoxia reduced myocardial glycogen approximately 30% and increased both the fraction of glycogen synthase in its physiologically active (GS I) form (from 0.24 +/- 0.06 to 0.82 +/- 0.07; P < 0.005) and glycogen synthesis (from 0.087 +/- 0.011 to 0.375 +/- 0.046 mumol.g-1.min-1; P < 0.005). Reducing cardiac work (with propranolol or heterotopic transplantation) reduced glycogen breakdown, glycogen synthase activation, and glycogen synthesis in parallel, stepwise fashion in intact rats. Correspondingly, hypoxia increased GS I activity in the perfused heart in vitro, but only under conditions where glycogen was consumed. This suggests myocardial glycogen synthase is activated by systemic hypoxia and catalyzes rapid posthypoxic glycogen synthesis. Hypoxic glycogen synthase activation appears to be a proportionate, wholly intrinsic response to local glycogenolysis, operating to preserve myocardial glycogen stores independent of any extracardiac mediator of carbohydrate metabolism.

Animals↗