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PubMed2002

Glassy cell carcinoma of the uterine cervix: histochemical, immunohistochemical, and molecular genetic observations.

Glassy cell carcinoma (GCC) of the uterine cervix is characterized by distinctive cytological features and an aggressive clinical course. Although this tumor has been usually considered a poorly differentiated variety of adenosquamous carcinoma (ASC), a clarification of the phenotype and histogenesis of GCC is still required. We examined three GCCs and four ASCs for histochemical and immunohistochemical phenotypes and molecular genetic status, comparing them with five nonkeratinizing squamous cell carcinomas and five endocervical-type mucinous adenocarcinomas. GCCs had a profile of cytokeratin expression similar to that of reserve cells or immature squamous cells of the cervix. In addition to squamous differentiation, GCCs sporadically produced intestinal-type mucin. HPV 18 was detected in two of three GCCs and two of four ASCs. GCCs may originate from multipotential stem or reserve cells that undergo early squamous differentiation. The presence of HPV 18 might stimulate biphasic squamous and glandular differentiation.

Adenocarcinoma, Mucinous↗

PubMed1999

Diversity of core promoter mutations in immune clearance phase of chronic HBV infection.

BACKGROUND/AIMS: Transcription of HBV (hepatitis B virus) pre-core and pre-genomic mRNAs is controlled by core promoter. Therefore, mutations in the core promoter region might change the activity of liver diseases through an altered transcriptional level of the mRNA. The present study was carried out to determine the diversity of HBV core promoter sequences in chronic HBV carriers. METHODS: DNA sequences in the core promoter region were determined after cloning the PCR product. Two groups of chronic HBV carriers with HBeAg, including five cases of asymptomatic carriers (ASCs, 21 clones) and eight with chronic hepatitis (CH, 50 clones) were studied. RESULTS: Mutations in the core promoter were found in three out of the ASCs (11 clones), and in all eight cases in the CH group (48 clones). While mutations at nucleotide 1762 (A-->T) and 1764(G-->A) were not found in ASC, mutations at the same positions were found in all the cases of CH group (40 clones) (P=0.003). Diverse patterns of mutations in the core promoter were observed in each patient in the CH group. CONCLUSIONS: Further studies are needed to determine whether the diversity of HBV core promoter mutations has clinical significance such as the seroconversion of HBeAg to anti-HBe.

Adult↗

PubMed2026

Efficacy and safety of split-dose ultra-low-volume polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate for bowel preparation: a systematic review and meta-analysis.

Colonoscopy remains the gold standard for early detection and prevention of colorectal cancer, with adequate bowel cleansing being pivotal for its success. This systematic review aims to evaluate the efficacy and safety of split-dose ultra-low-volume polyethylene glycol (PEG) with ascorbic acid (Asc) versus sodium picosulfate magnesium citrate for bowel preparation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search across Embase, PubMed, Web of Science, and Scopus from inception to July 2025. Data analysis was conducted using R version 4.2.2 (31 October 2022) and RStudio version 2022.07.2 (2009-2022, RStudio, Inc.) Our literature search yielded six eligible studies involving 3285 patients. Our findings indicate no significant differences in overall and right-sided colon adequate cleansing rates between the two regimens: risk ratio: 1.05, 95% confidence interval (CI): 0.99-1.12, P  = 0.1082; and risk ratio: 1.03, 95% CI: 0.99-1.08, P  = 0.1755, respectively. However, PEG + Asc demonstrated a significantly lower rate of vomiting compared to sodium picosulfate magnesium citrate (risk ratio: 2.58, 95% CI: 0.94-2.78, P  = 0.0008), suggesting better tolerability. Other secondary outcomes, including nausea, abdominal pain, and overall Boston Bowel Preparation Scale scores, did not show significant differences. The quality of the evidence varied across the outcomes. Our results support the comparable efficacy of both bowel preparation agents while highlighting PEG + Asc's potential advantages in tolerability. Our findings suggest that the choice between these two preparations can be tailored to the specific patient, considering their preferences or previous experiences, although some caution is advised in interpreting these findings.

Humans↗

PubMed1980

Amino acid transport in human and in sheep erythrocytes.

Amino acid transport was compared in human and in sheep erythrocytes. Kinetic studies established that human cells have three discrete amino acid transport systems, designated L, Ly+ and ASC. The L system is partially stereospecific, with a preference for large neutral amino acids. L-leucine has a threefold lower apparent Km and a twofold smaller Vmax than D-leucine. Alanine, cysteine and possibly dibasic amino acids are transported by this route, but with a low affinity. The Ly+ system is highly stereoselective, and specific for dibasic amino acids, including arginine. The ASC system is Na-dependent and selective for neutral amino acids of intermediate size. It has a particularly low apparent Km for cysteine and is stereospecific. Sheep erythrocytes lack these systems. Instead they possess an additional system (C system) responsible for the transport both of neutral and of dibasic amino acids, with cysteine as the optimal substrate. Although the substrate specificities of the human ASC and sheep C systems are similar, the sheep system does not require Na and has considerably higher apparent Km values. Dibasic amino acid transport (of lysine, but not of arginine) by the C system occurs with a low affinity.

Amino Acids↗

PubMed2002

Changes in the antioxidant systems as part of the signaling pathway responsible for the programmed cell death activated by nitric oxide and reactive oxygen species in tobacco Bright-Yellow 2 cells.

Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS), for the activation of the hypersensitive reaction, a defense response induced in the noncompatible plant-pathogen interaction. However, its involvement in activating programmed cell death (PCD) in plant cells has been questioned. In this paper, the involvement of the cellular antioxidant metabolism in the signal transduction triggered by these bioactive molecules has been investigated. NO and ROS levels were singularly or simultaneously increased in tobacco (Nicotiana tabacum cv Bright-Yellow 2) cells by the addition to the culture medium of NO and/or ROS generators. The individual increase in NO or ROS had different effects on the studied parameters than the simultaneous increase in the two reactive species. NO generation did not cause an increase in phenylalanine ammonia-lyase (PAL) activity or induction of cellular death. It only induced minor changes in ascorbate (ASC) and glutathione (GSH) metabolisms. An increase in ROS induced oxidative stress in the cells, causing an oxidation of the ASC and GSH redox pairs; however, it had no effect on PAL activity and did not induce cell death when it was generated at low concentrations. In contrast, the simultaneous increase of NO and ROS activated a process of death with the typical cytological and biochemical features of hypersensitive PCD and a remarkable rise in PAL activity. Under the simultaneous generation of NO and ROS, the cellular antioxidant capabilities were also suppressed. The involvement of ASC and GSH as part of the transduction pathway leading to PCD is discussed.

Antioxidants↗

PubMed2004

Production of reactive oxygen species, alteration of cytosolic ascorbate peroxidase, and impairment of mitochondrial metabolism are early events in heat shock-induced programmed cell death in tobacco Bright-Yellow 2 cells.

To gain some insight into the mechanisms by which plant cells die as a result of abiotic stress, we exposed tobacco (Nicotiana tabacum) Bright-Yellow 2 cells to heat shock and investigated cell survival as a function of time after heat shock induction. Heat treatment at 55 degrees C triggered processes leading to programmed cell death (PCD) that was complete after 72 h. In the early phase, cells undergoing PCD showed an immediate burst in hydrogen peroxide (H2O2) and superoxide (O2*-) anion production. Consistently, death was prevented by the antioxidants ascorbate (ASC) and superoxide dismutase (SOD). Actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively, also prevented cell death, but with a lower efficiency. Induction of PCD resulted in gradual oxidation of endogenous ASC; this was accompanied by a decrease in both the amount and the specific activity of the cytosolic ASC peroxidase (cAPX). A reduction in cAPX gene expression was also found in the late PCD phase. Moreover, changes of cAPX kinetic properties were found in PCD cells. Production of ROS in PCD cells was accompanied by early inhibition of glucose (Glc) oxidation, with a strong impairment of mitochondrial function as shown by an increase in cellular NAD(P)H fluorescence, and by failure of mitochondria isolated from cells undergoing PCD to generate membrane potential and to oxidize succinate in a manner controlled by ADP. Thus, we propose that in the early phase of tobacco Bright-Yellow 2 cell PCD, ROS production occurs, perhaps because of damage of the cell antioxidant system, with impairment of the mitochondrial oxidative phosphorylation.

Apoptosis↗

PubMed2004

Fruit acids and sodium hydroxide in the food industry and their combined effect with sodium lauryl sulphate: controlled in vivo tandem irritation study.

BACKGROUND: Cutaneous exposure to a variety of irritants has been extensively studied in recent years. Nevertheless, knowledge of the induction of irritant dermatitis, especially by mild irritants at low doses and for a short duration of exposure, is still incomplete. OBJECTIVES: To quantify the irritant effects and barrier disruption properties of ascorbic acid (ASC), acetic acid (ACA) and sodium hydroxide (NaOH), particularly in combination with an anionic detergent, sodium lauryl sulphate (SLS). METHODS: In a tandem repeated irritation test, the irritants were applied for 30 min twice daily for 4 days to the skin of the mid-back of 19 healthy volunteers of both sexes. We used bioengineering techniques for measurement of transepidermal water loss (TEWL) and skin colour reflectance, as well as visual scoring. RESULTS: Repeated application of ASC and ACA caused a moderate increase in TEWL and erythema. The sequential application of ASC or ACA and SLS enhanced these effects. NaOH induced a strong reaction when applied both occlusively and nonocclusively as well as in combination with SLS, with an early onset of the inflammatory signs, leading to discontinuation of the application on the third day in most of the test fields. Notably, the irritant effect of NaOH was not as marked when applied sequentially with SLS. CONCLUSIONS: Our results demonstrate that concurrent application of an anionic detergent and a mild acidic irritant can lead to disruption of the barrier function which, although not additive, is still considerable. The combined application of SLS and mild acids does not prevent SLS-induced irritation. Furthermore, we showed that NaOH in low concentrations may also act as a potent irritant but that its effect is not enhanced by SLS. The necessity of adequate skin protection and reduction of contact with substances that are potentially barrier disruptive and irritant, e.g. in the food industry, is emphasized, not only when handling detergents, but also when processing food products.

Acetic Acid↗

PubMed2005

Differential expression of chemokine receptors on human IgA+ and IgG+ B cells.

Organ-specific lymphocyte homing is dependent on the expression of tissue-specific homing receptors and selected chemokine receptors. During the effector phase of an immune response, IgA and IgG antibody-secreting cells (ASC) are differently distributed in the body. Still, B cell expression of L-selectin and the mucosal homing receptor integrin alpha4beta7 is not related to the isotype produced, but only to the site of antigen encounter. In this study, we examined if differences in chemokine responsiveness between IgA+ and IgG+ B cells could explain their different tissue localization. Circulating CD19+ B cells were isolated and their expression of IgA, IgG, and selected chemokine receptors was determined by flow cytometry. Few Ig+ cells expressed CCR2, CCR3, or CCR9, and there was no difference in the expression of these receptors between IgA+ and IgG+ cells. In contrast, CCR4, CCR5, and CXCR3 was expressed on significantly more IgG+ than IgA+ cells. The function of chemokine receptors on memory B cells and ASC was then tested in the transwell system. IgG+ memory cells migrated to a higher extent than IgA+ cells towards the CXCR3 ligand CXCL11/I-TAC, while there was only a small migration towards the CCR4 ligand CCL17/TARC and the CCR9 ligand CCL25/TECK. ASC migrated poorly to all chemokines tested. In conclusion, this study shows that IgG+ and IgA+ memory B cells have a differential expression of the Th1 associated chemokine receptor CXCR3, as well as of CCR4 and CCR5. In contrast, none of the studied chemokine receptors was preferentially expressed by IgA+ cells.

Antibody-Producing Cells↗

PubMed2006

Rapid rescreening of cervical smears as a quality control method in a high-risk population.

OBJECTIVE: Cancer of the cervix is one of the commonest cancers in South Africa. Accurate cytological diagnosis is one of the prerequisites for an effective cervical screening programme and requires the implementation of appropriate quality assurance modalities. This study was undertaken to determine if rapid review of reportedly negative cervical smears is a useful internal quality assurance modality in an unscreened population with very high rates of cervical carcinoma. METHOD: Approximately 26% of all cervical smears received at the study institution between 1 January 1998 and 31 December 2003, and initially reported as negative or inadequate, underwent rapid review. RESULTS: A total of 62,866 (26%) cervical smears out of 241,796 reportedly negative or inadequate cervical smears underwent rapid review. An amended report was sent out in 373 (0.59%) of these 62,866 cervical smears. This included 101 cases of high-grade squamous intraepithelial lesion (HSIL) and high-grade atypical squamous cells (ASC-H), 143 low-grade squamous intraepithelial lesions, 54 atypical squamous cells of undetermined significance (ASC-US) and 33 atypical glandular cells that were not reported initially. The false-negative proportion for HSIL and ASC-H (combined) in this study was 5.76%. No squamous cell carcinomas were diagnosed on rapid review but one patient with HSIL/ASC-H on review had squamous cell carcinoma on biopsy. Three cytotechnologists had a lower sensitivity of primary screening and required retraining. CONCLUSIONS: Rapid review is beneficial as an internal quality assurance modality in an unscreened high-risk population and increases the detection of women with significant cervical lesions requiring treatment. The relatively low cost of rapid review compared with other rescreening modalities makes this an attractive option in low resource settings.

Female↗

PubMed1994

Ascorbic acid reduces the endotoxin-induced lung injury in awake sheep.

Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite-mediated acute lung injury. The effects of intravenous administration of Escherichia coli endotoxin were studied, with and without ascorbic acid infusion, on haemodynamics, lung lymph flow, cardio-respiratory and neutrophil function in chronically instrumented sheep. Paired experiments were performed on eight sheep in which they received either endotoxin alone (0.5 micrograms kg-1 b.w.) (ET group) or in combination with an ascorbic acid infusion (1 g kg-1 b.w. bolus injection followed by 0.2 g kg-1 h-1 continuous infusion) ET + ASC group) in random order. Four of the animals also received ascorbic acid alone (ASC group). As a result, for the ET + ASC group a general and mostly significant improvement (P < 0.05) in the early hypertensive phase (0-60 min, P values) and in the late permeability phase (2-4 h, *P values) of cardiorespiratory function (mean artery pressure: P/*P = 0.283/0.049; mean pulmonary artery pressure: P/*P = 0.0001/0.0001; mean pulmonary artery wedge pressure: P/*P = 0.012/0.001; right ventricular stroke work index: P/*P = 0.02/0.0001; cardiac index: P/*P = 0.797/0.755; arterial oxygen saturation: P/*P = 0.0059/0.01; arterial-venous difference of oxygen tension: P/*P = 0.011/0.0005), oxygen consumption: P/*P = 0.013/0.035, lung lymph flow: P/*P = 0.562/0.012, lymph/plasma protein ratio: P/*P = 0.304/0.008 and protein clearance: P/*P = 0.56/0.05 was observed in comparison with the ET group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Evaluation of a pharmacist-managed anticoagulation clinic.

Medical records were retrospectively analyzed to evaluate the success of a pharmacist-managed Anticoagulation Surveillance Clinic (ASC). The 78 patients in group I were followed by the ASC. The 17 patients in Group II were followed by other Veterans Administration Medical Center clinics. Demographic characteristics, warfarin indication and potentially complicating conditions were comparable between the groups. Group I patients had shorter intervals between visits to the clinic than Group II patients. Although not statistically different compared to Group II, Group I patients had better prothrombin time control. Group I patients also had fewer complications per treatment year (6.9% vs 9.0%) and received fewer potentially interacting drugs. The ASC was at least as successful as the other clinics in managing patients on warfarin, and results compared very favorably to those reported in the literature for other anticoagulation clinics.

Ambulatory Care Facilities↗

PubMed2005

Host immune reactions and worm kinetics during the expulsion of Ascaris suum in pigs.

Pigs single inoculated with Ascaris suum eggs expel the majority of larvae between days 14 and 21 post inoculation (p.i.), but the role of the immune system in expulsion is unclear. To investigate the dynamics of immune responses before, during and after the expulsion of A. suum larvae, pigs inoculated with 10 000 A. suum eggs were sequentially necropsied. Ascaris suum gradually moved distally from days 10-14 p.i. and only a few larvae were left by day 21 p.i. Pronounced increases in mucosal A. suum-specific IgA antibody secreting cells (ASCs) were already found by day 10 p.i. especially in the proximal jejunum, while only small increases in parasite-specific IgM ASCs were observed by day 21 p.i. in both proximal and distal jejunum. No mucosal IgG ASC responses could be detected. Increases in systemic A. suum-specific IgG1, IgM and to a lesser extent IgA antibodies were observed, while IgG2 remained almost unchanged. The levels of eosinophils and mast cells in the small intestinal mucosa did not change throughout infection. The results demonstrate that both systemic and mucosal A. suum-specific effector mechanisms are strongly stimulated in A. suum single infections and indicate that mucosal IgA may be an important mediator in the expulsion of A. suum.

Animals↗

PubMed1988

Cellular immune responses in the murine lung to local immunization with influenza A virus glycoproteins in micelles and immunostimulatory complexes (iscoms).

Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.

Animals↗

PubMed1979

Formation of aminosuccinyl peptides during acidolytic deprotection followed by their transformation to piperazine-2,5-dione derivatives in neutral media.

Prolonged acidic treatment of Boc-Leu-Asp(OBut)-Phe-NH2 with 4N HCl in acetic acid resulted in H-Leu-Asc-Phe-NH2 . HCl(Asc, aminosuccinyl), which transformed partially to cyclo[Leu-Asp(Phe-NH2)] during its purification by column chromatography on silica gel with a mixture of ethyl acetate/pyridine/acetic acid/water = 60:20:6:11, i.e. in neutral medium. Examination of the imide formation was extended to different reaction conditions (no imide derivative was detected in trifluoroacetic acid), to several protected derivatives of L-aspartyl-L-phenylalaninamide and to tripeptides containing an aspartyl residue in the middle position. It was clearly demonstrated that in strongly acidic media the imide derivatives are directly formed from the aspartyl peptides containing a free beta-carboxyl group. The influence of the C-terminal residue was greater than the N-terminal on both the rate of formation of the imide and its further transformation to piperazine-2,5-dione derivative. In aqueous ethanol the X-Asc-Y-NH2 (X, Pro, Leu; Y, Gly, Ala, Val, Phg, Phe) containing N-terminal proline are more readily transformed to piperazine-2,5-dione derivatives, but compared to simple proline dipeptides the rate of this transformation is relatively slow because of the crowdedness of the tricyclic transitional state.

Amino Acid Sequence↗

PubMed2006

Olaquindox and cyadox stimulate growth and decrease intestinal mucosal immunity of piglets orally inoculated with Escherichia coli.

One hundred and fifty piglets were randomly allotted to one of six treatments to determine the effects of olaquindox and cyadox on growth and intestinal immune response including the number of intraepithelial lymphocytes and immunoglobulin A secreting cells (ASCs) during the three-week period. A 2 x 3 factorial arrangement of treatments was employed with the following factors: (1) Escherichia coli (O(139):K(88), 10(10) CFU) inoculation or control and (2) no antimicrobials, 100 mg/kg olaquindox and 100 mg/kg cyadox in the basal diet respectively. The antimicrobial supplementations improved (p < 0.01) average daily gain and feed conversion ratio (FCR) during the experiment. Average daily gain and FCR in the cyadox-supplemented pigs were higher (p < 0.05) than those in the olaquindox-supplemented pigs. Intraepithelial lymphocytes and ASCs decreased (p < 0.05) when the diets were supplemented. Jejunal ASCs in the cyadox-supplemented pigs were lower (p < 0.05) than those in the olaquindox-supplemented pigs. Olaquindox and cyadox suppressed E. coli-induced intestinal immune activation, which may be involved in the observed growth promotion.

Animal Feed↗

PubMed1981

Cysteine and cystine transport at the blood-brain barrier.

The nature of cysteine and cystine uptake from the cerebral capillary lumen was studied in the rat using the carotid injection technique, [35S]-Cysteine uptake was readily inhibited by the synthetic amino acid 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), the defining substrate for the leucine-preferring (L) system in the Ehrlich ascites cell. The addition of nonradioactive alanine or serine, representatives of the alanine, serine, and cysteine-preferring (ASC) system, produced no significant decrease in the uptake of cysteine after cysteine transport by the L system was blocked with BCH. This indicated that the major component of cysteine's transport from the brain capillary lumen was by the L system with no detectable uptake of cysteine by the ASC system. No carrier-mediated transport of cystine, the disulfide form of the amino acid, was detected, nor was there any inhibition by cystine of the transport of the neutral amino acid methionine or the basic amino acid arginine. These results suggest that the ASC system, if present, is not quantitatively important for the transport of neutral amino acids from the brain capillary lumen.

Amino Acids↗

PubMed1992

Catheter ablation of ventricular tachycardia: role of the underlying etiology and the site of energy delivery.

The role of DC catheter ablation (CA) to treat patients with sustained monomorphic ventricular tachycardia (VT) is still debated. To assess the efficacy of VT CA, we studied the follow-up of 49 patients with VT who underwent CA. There were 33 patients with an old myocardial infarction (MI) (group G I) and 16 patients had noncoronary VT (group G II): CA was performed at the earliest endocardial activation (EEA) (20 patients in G I, 14 patients in G II) or at the area of slow conduction (ASC) (13 patients in G I, 2 patients in G II). During the mean follow-up of 35 +/- 25 (1-79) months, there were 17 patients in G I (52%) and 12 patients in G II (75%) with VT recurrences (P less than 0.05). Recurrences of VT was observed in 4 of 15 patients (27%) when CA was performed at the ASC, compared to 25 of 34 patients (74%) with CA at the EEA (P less than 0.01). These data show that DC CA is more successful in patients with coronary artery disease, particularly when CA is performed at the ASC.

Adult↗

PubMed2000

Kinetics of the mucosal antibody secreting cell response and evidence of specific lymphocyte migration to the lung after oral immunisation with attenuated S. enterica var. typhimurium.

The kinetic of mucosal secretory responses elicited by the vaccine vector Salmonella enterica var. typhimurium (S. typhimurium) was examined by enzyme linked immunospot (ELISPOT) and compared with serum responses. Mice immunised orally with BRD509, the aroA, aroD mutant of virulent S. typhimurium SL1344 expressing the C Fragment of tetanus toxin (TT), simultaneously developed an IgA antibody secreting cells (ASC) response in the gastrointestinal lamina propria, the spleen and the lung, against both S. typhimurium lipopolysaccharide (LPS) and TT. The magnitude of the ASC response was greatest in the gut, was boosted by a secondary immunisation at day 25, and the kinetic of the response did not correlate with the appearance of serum antibodies. This study suggests that S. typhimurium can engage the common mucosal immune system to effect mucosal secretory responses at distal sites, however, the magnitude of the responses is both greatest in the gut and antigen-specific. The ASC origin of the serum antibodies specific for S. typhimurium and antigens expressed by the bacterium is yet to be elucidated.

Animals↗