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At least 559 records · Page 31Linked to original sources
PubMed2006

Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy.

BACKGROUND: Lactobacillus- and Bifidobacterium-containing yogurt (AB-yogurt) can suppress Helicobacter pylori. Improvement of the eradication rate by quadruple therapy of residual H. pylori after failed triple therapy is needed. OBJECTIVE: We tested whether prior treatment with AB-yogurt improved the efficacy of quadruple therapy in eradicating residual H. pylori after failed triple therapy. DESIGN: One hundred thirty-eight patients in whom triple therapy failed were enrolled for a culture study of H. pylori to assess antimicrobial resistance. These patients were then randomly assigned in equal numbers to either a yogurt-plus-quadruple therapy group or a quadruple therapy-only group. The patients received 1 wk of quadruple therapy with or without a 4-wk pretreatment with AB-yogurt (400 mL/d). In the yogurt-plus-quadruple group, excessive delta(13)CO(2)/mL values of the (13)C-urea breath test were collected before and every 2 wk during the 4-wk ingestion of yogurt. For both groups, a (13)C-urea breath test was conducted > or =6 wk after the quadruple therapy to assess the outcome of residual H. pylori eradication. RESULTS: For the patients in the yogurt-plus-quadruple therapy group infected with either antibiotic-sensitive or -resistant H. pylori, the excessive delta(13)CO(2)/mL values of the (13)C-urea breath test were significantly decreased after the 4-wk ingestion of AB-yogurt (P < 0.0001). The yogurt-plus-quadruple therapy group had a higher H. pylori eradication rate than did the quadruple therapy-only group (intention-to-treat analysis: 85% compared with 71.1%, P < 0.05; per-protocol analysis: 90.8% compared with 76.6%, P < 0.05). CONCLUSION: A 4-wk pretreatment with AB-yogurt can decrease H. pylori loads despite antimicrobial resistance, thus improving the efficacy of quadruple therapy in eradicating residual H. pylori.

Anti-Bacterial Agents↗
PubMed2006

Involvement of mitochondria and caspase pathways in N-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell.

AIM: To study the mechanisms by which N-demethyl-clarithromycin (NDC) induces human cervical cancer HeLa cell apoptosis in vitro. METHODS: The viability of N-demethyl-clarithromycin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Measurement of mitochondrial transmembrane potential was analyzed by a FACScan flowcytometer. Caspase-3, poly-(ADP-ribose) polymerase (PARP), caspase-activated DNase (ICAD), Bcl-2, Bax, p53, and SIRT1 protein expression and the release of cytochrome c were detected by Western blot analysis. RESULTS: N-demethyl-clarithromycin, an anti-inflammatory substance, inhibited HeLa cell growth in a dose- and time-dependent manner. N-demethyl-clarithro-mycin induced HeLa cell death through the apoptotic pathways. The pan-caspase inhibitor (z-VAD-fmk), caspase-3 inhibitor (z-DEVD-fmk) and the caspase-9 inhibitor (z-LEHD-fmk) partially enhanced cell viability induced by N-demethyl-clarithromycin, but the caspase-8 inhibitor (z-IETD-fmk) had almost no effect. Caspase-3 was activated then followed by the degradation of caspase-3 substrates, the inhibitor of ICAD and PARP. Simultaneously, mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c in the cytosol was increased. N-demethyl-clarithromycin upregulated the expression ratio of mitochondrial Bax/Bcl-2, and significantly increased the expression of the p53 protein. It also downregulated anti-apoptotic protein SIRT1 expression. CONCLUSION: N-demethyl-clarithromycin induced apoptosis in HeLa cells via the mitochondrial pathway.

Anti-Inflammatory Agents↗
PubMed2006

Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. AIM: To assess the impact of infliximab on bone oedema in PsA as shown by MRI. METHODS: 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). RESULTS: At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. CONCLUSIONS: Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.

Adult↗
PubMed2006

Expression of type 5 somatostatin receptor in TSH-secreting pituitary adenomas: a possible marker for predicting long-term response to octreotide therapy.

In TSH-secreting pituitary adenomas (TSHoma), octreotide (OCT) therapy reduces tumor size and TSH secretion in some cases but not in others. As OCT acts through various types of somatostatin receptors (SSTRs), the different responses of TSHoma to OCT might be explained by the differences of SSTR expression. We therefore studied the expression of subtype-specific SSTR mRNA transcripts in tumor tissues by RT-PCR. Type 2 (SSTR2) mRNA transcripts were detected in all 8 tumors but those of SSTR3 and SSTR5 were demonstrated only in 5 of them. Serum TSH levels were decreased by OCT administration test in all patients but OCT therapy was effective in two patients out of three. SSTR5 mRNA was detected in two tumors from the responder, but not in one tumor that was resistant to OCT. These observations suggest that the temporal decrease of TSH by OCT may be mediated by SSTR2, and that the long term response to OCT therapy may be related with the expression of SSTR5. Therefore, the expression of SSTR5 in TSHoma may be a useful marker for predicting the outcome of the therapy, but further studies with larger numbers of patients are necessary.

Adenoma↗
PubMed2002

[Correlation of protein kinase C activity and its subcellular distrubution with multidrug resistance in KVB200 cells].

OBJECTIVE: To investigate the relationship between protein kinase C (PKC) and multidrug resistance (MDR) in cancer cell line KBV200. METHODS: MTT assay was used to evaluate the IC50 of vincristine (VCR) and adriamycin (ADR) in KB cell line and its VCR-resistant derivative KBV200 cells. PKC activities in the 2 cell lines were assayed by measuring the incorporation of (32)P from [gamma-(32)P] ATP into the peptide substrates. RESULTS: The IC50 values of VCR and ADR in KBV200 cells was 64.03 and 18.8 folds greater than those in KB cells. PKC activities of the membrane and cytosol fraction in KBV200 cells were increased compared with that in KB cells, with the total PKC activity 1.12-fold higher. Phorbol-12-myristate-13 -acetate increased PKC activity of the membrane fraction and IC50 values of KBV200 cells, while staurosporine worked to the opposite effects. CONCLUSION: PKC may contribute to MDR mechanism in KBV200 cells.

Antineoplastic Agents↗
PubMed2003

[Effects of naloxone on rat cortical neuron apoptosis induced by anoxia].

OBJECTIVE: To investigate the damage of anoxia on the cultured rat's cortical neurons and the protective effects of naloxone. METHODS: Cortical neurons cultured for 12 days were randomly divided into three groups: control, anoxic group and anoxic group plus naloxone treated. Cortical neurons were exposed to anoxic environment for 6 hours and then cultured for 24 hours under normoxic condition. The apoptosis of neurons was detected with the method of TdT-mediated dUTP nick end labeling (TUNEL) and the apoptotic rate of neurons was measured using flow cytometry. RESULTS: Anoxia could lead to increasing apoptosis and death of rate cortical neurons. Naloxone could reduce neuron apoptosis. There was a significant difference between the anoxic group and anoxic group plus naloxone (P<0.01). CONCLUSION: Naloxone can ameliorate the toxicity damage of neurons caused by anoxia through reducing neuron apoptosis, which suggests that naloxone could protect rat's cortical neurons from damage under anoxia condition.

Animals↗
PubMedDate not supplied

Neuropharmacological correction of cognitive processes disrupted by extirpation of the AI-AII and Ep fields in cats.

An original neuropsychophysiological battery of tests was used to study the possibility of neuropharmacological correction of compensatory-restorative processes in cats after extirpation of a defined zone of the temporal cortex; studies were carried out in conditions of free behavior. In a variety of activation and inhibition regimes, systemic administration of cholinergic, dopaminergic, GABAergic, and serotoninergic agents could have favorable effects on restorative mechanisms, depending on cortical psycho-organic symptoms. Each cognitive activity studied (perception, gnosis, thought) had its own specific positive neuromediator "profile" in terms of compensatory outcomes.

Animals↗
PubMed2003

Arterial ischemic strokes in infants and children: an overview of current approaches.

Stroke in children is increasingly recognized. The incidence exceeds 8 per 100,000 per year. Important differences in stroke in newborns and children compared with adults, as well as a paucity of clinical trials, create challenges in the diagnosis and management of pediatric arterial ischemic stroke (AIS). The neurological presentation of AIS can be subtle. Radiographic diagnosis of acute AIS is also challenging because CT scan may be normal early on. Risk factors include vascular, intravascular, and embolic disorders; frequently, there are multiple risk factors in a given child, necessitating thorough investigations. More than 50% have a vasculopathy including postvaricella angiopathy, dissection, moyamoya, or vasculitis. Intravascular mechanisms are frequently present, including dehydration. Hematological or prothrombotic conditions are also associated with AIS in children, and include sickle cell disease and prothrombotic disorders. The latter have been identified in from one third to one half of children with AIS, are usually acquired, and frequently act in concert with other risk factors for stroke. The most common embolic source is congenital heart disease, which is present in 25% of children with AIS. Outcomes include death in 6% and neurological deficits in two thirds of children. Given that no clinical trials have been completed in pediatric stroke to date, treatment is empiric. Initial neuroprotective strategies aim to reduce the size of the infarct. For older children antithrombotic agents (antiplatelet drugs and anticoagulants) are given to reduce the 20 to 30% risk of recurrence. There are coordinated research efforts currently being initiated, which over the next decade will result in clinical trials in this understudied condition.

Arterial Occlusive Diseases↗
PubMed2003

Bacteria-host communication: the language of hormones.

The interbacterial communication system known as quorum sensing (QS) utilizes hormone-like compounds referred to as autoinducers to regulate bacterial gene expression. Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is the agent responsible for outbreaks of bloody diarrhea in several countries. We previously proposed that EHEC uses a QS regulatory system to "sense" that it is within the intestine and activate genes essential for intestinal colonization. The QS system used by EHEC is the LuxS/autoinducer 2 (AI-2) system extensively involved in interspecies communication. The autoinducer AI-2 is a furanosyl borate diester whose synthesis depends on the enzyme LuxS. Here we show that an EHEC luxS mutant, unable to produce the bacterial autoinducer, still responds to a eukaryotic cell signal to activate expression of its virulence genes. We have identified this signal as the hormone epinephrine and show that beta- and alpha-adrenergic antagonists can block the bacterial response to this hormone. Furthermore, using purified and in vitro synthesized AI-2 we showed that AI-2 is not the autoinducer involved in the bacterial signaling. EHEC produces another, previously undescribed autoinducer (AI-3) whose synthesis depends on the presence of LuxS. These results imply a potential cross-communication between the luxS/AI-3 bacterial QS system and the epinephrine host signaling system. Given that eukaryotic cell-to-cell signaling typically occurs through hormones, and that bacterial cell-to-cell signaling occurs through QS, we speculate that QS might be a "language" by which bacteria and host cells communicate.

Bacterial Proteins↗
PubMed2006

Effects of feed additives and mixed eimeria species infection on intestinal microbial ecology of broilers.

Evaluation of digestive microbial ecology is necessary to understand effects of growth-promoting feed. In the current study, the dynamics of intestinal microbial communities (MC) were examined in broilers fed diets supplemented with a combination of antibiotic (bacitracin methylene disalicylate) and ionophore (Coban 60), and diets containing 1 of 2 essential oil (EO) blends, Crina Poultry (CP) and Crina Alternate (CA). Five treatments were analyzed: 1) unmedicated uninfected control; 2) unmedicated infected control; 3) feed additives monensin (bacitracin methylene disalicylate) + monensin (Coban 60; AI); 4) EO blend CP; and 5) EO blend CA. Additives were mixed into a basal feed mixture, and EO were adjusted to 100 ppm. Chicks were infected by oral gavage at 19 d of age with Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Duodenal, ileal, and cecal samples were taken from 12 birds per treatment just before and 7 d after challenge; 2 samples each were pooled to give a final number of 6 samples total; and all pooled samples were frozen until used for DNA extraction. Denaturing gradient gel electrophoresis was used to examine PCR-amplified fragments of the bacterial 16S ribosomal DNA variable region. Results are presented as percentages of similarity coefficients (SC). Dendrograms of PCR amplicon or band patterns indicated MC differences due to intestinal location, feed additives, and cocci challenge. Essential oil blends CP and CA affected MC in all gut sections. Each EO had different effects over MC, and they differed in most instances from the AI group. The cocci challenge caused drastic MC population shifts in duodenal, ileal, and cecal sections (36.7, 55.4, and 36.2% SC, respectively). Diets supplemented with CP supported higher SC between pre- and postchallenge MC (89.9, 83.3, and 76.4%) than AI (81.8., 57.4, and 60.0%). We concluded that mixed coccidia challenge caused drastic shifts in MC. These EO blends modulated MC better than AI, avoiding drastic shifts after a mixed challenge.

Animal Feed↗
PubMed1998

Characterization of uterine leukocyte infiltration in gilts after artificial insemination.

The objective of this study was to characterize the uterine leukocyte influx after artificial insemination (AI). After detection of oestrus with a boar at intervals of 1.5 h, seventy-two gilts were randomly assigned to a 2 x 3 x 4 factorial arrangement. AI was performed with 100 ml extended semen containing 5 x 10(9) spermatozoa (semen; n = 36) or 100 ml VSP semen extender (extender; n = 36) at one of three times after detection of oestrus: 12, 24 or 36 h (n = 24/time). The uterus was lavaged at 6, 12, 18 or 24 h (n = 18/time) after AI to determine the total number of uterine leukocytes. In addition, uterine lavage was performed on nine untreated gilts immediately after the detection of oestrus to establish a baseline number of leukocytes. The leukocyte response in all samples consisted predominately (92-99%) of polymorphonuclear neutrophilic granulocytes (PMNs). The mean number of PMNs recovered from the uteri of gilts treated with semen was greater than in gilts treated with extender and in untreated gilts (P < 0.01). The greatest number of PMNs in semen-treated gilts was found 12 h after AI (P < 0.01), and this number was sustained for 24 h. In contrast, the number of uterine PMNs recovered from extender-treated gilts reached a peak at 6 h and had declined by 12 h after AI (P < 0.05). It was concluded that an extensive influx of PMNs into the uterus is a normal sequence to AI. The consequences and importance of semen-induced uterine leukocytosis needs further investigation.

Analysis of Variance↗
PubMed2002

[Affection of neoadjuvant chemotherapy on cell apoptosis and proliferation in breast cancer].

BACKGROUND & OBJECTIVE: Although the researches had verified various kinds of chemotherapic agents can cause the apoptosis of breast cancer cells, but the reports with in vivo data are still scarce. This paper is to investigate whether neoadjuvant chemotherapy could induce tumor cell apoptosis in breast cancer patients, and its effect on cell proliferation. METHODS: Apoptosis index (AI) of tumor cells is assayed by TdT-mediated dUTP nick end labeling(TUNEL) and proliferating cell nuclear antigen (PCNA) is examined by immunohistochemical labelled streptavidin biotin (ISAB) in 100 beast cancer samples. RESULTS: Tumor cell AI in neoadjuvant group (mean = 7.47%) was significantly higher than that in control group (mean = 4.83%) (P < 0.01). PCNA positive expression rate in neoadjuvant group (mean = 33.71%) was significantly lower than that in control group (mean = 51.52%) (P < 0.01). There was significant negative association between AI and PCNA in both neoadjuvant chemotherapy group and control group (P < 0.05). CONCLUSION: Neoadjuvant chemotherapy could induce tumor cell apoptosis and inhibit tumor cell proliferation in human breast cancer.

Apoptosis↗
PubMed2005

Effect of plasmin on laminin and fibronectin during plasmin-assisted vitrectomy.

OBJECTIVE: To determine whether plasmin will cleave the laminin and fibronectin located at the vitreoretinal junction during plasmin-assisted vitrectomy. METHODS: Western blot analyses were performed with antilaminin or anti-fibronectin antibodies on the internal limiting membranes collected from patients with macular holes or cystoid macular edema who underwent vitrectomy with or without plasmin. The results were compared with the results of in vitro experiments in which commercially available laminin and fibronectin were exposed to commercially available plasmin. RESULTS: In all eyes treated with plasmin, a posterior vitreous detachment was not present before surgery but was created easily with a minimal suction of less than 100 mm Hg during vitrectomy. Western blot analyses showed that the laminin and fibronectin in the internal limiting membrane exposed to plasmin during vitrectomy were degraded to several fragments of lower molecular weights, including a fragment of approximately 13,000 Da for laminin and a fragment of approximately 30,000 Da for fibronectin. These lower-molecular-weight fragments also appeared in the in vitro experiments. CONCLUSION: The laminin and fibronectin at the vitreoretinal junction are degraded during plasmin-assisted vitrectomy. CLINICAL RELEVANCE: These findings provide evidence for the efficacy of using plasmin to create a posterior vitreous detachment during vitreoretinal surgery.

Basement Membrane↗
PubMed2005

Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design.

In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2002

Involvement of redox events in caspase activation in zinc-depleted airway epithelial cells.

Airway epithelial cells (AEC) contain both pro- and anti-apoptotic factors but little is known about mechanisms regulating apoptosis of these cells. In this study we have examined the localization of pro-caspase-3 and Zn(2+), a cellular regulator of pro-caspase-3, in primary sheep and human AEC. Zn(2+) was concentrated in both cytoplasmic vesicles and ciliary basal bodies, in the vicinity of both pro-caspase-3 and the antioxidant Cu/Zn superoxide dismutase (Cu/Zn SOD). Depletion of intracellular Zn(2+) in sheep AEC, using the membrane permeant Zn(2+) chelator TPEN, increased lipid peroxidation in the apical cell membranes (as assessed by immunofluorescence with anti-hydroxynonenal) as well as increasing activated pro-caspase-3 and apoptosis. There were smaller increases in caspase-2 and -6 but not other caspases. Activation of caspase-3 in TPEN-treated AEC was inhibited strongly by N-acetylcysteine and partially by vitamin C and vitamin E. These findings suggest that cytoplasmic pro-caspase-3 is positioned near the lumenal surface of AEC where it is under the influence of Zn(2+) and other anti-oxidants.

Animals↗
PubMed2002

Polymorphisms and the differential antiviral activity of the chicken Mx gene.

The nucleotide sequence of chicken Mx cDNA was reported earlier using the White Leghorn breed in Germany, but it showed no enhanced resistance to viruses. In this study, the nucleotide sequences of chicken Mx cDNA were determined in many breeds. A total of 25 nucleotide substitutions, of which 14 were deduced to cause amino acid exchanges, were detected, suggesting that the chicken Mx gene is very polymorphic. Transfected cell clones expressing chicken Mx mRNA were established after the Mx cDNA was constructed with an expression vector and introduced into mouse 3T3 cells, and the Mx genes from some breeds were demonstrated to confer positive antiviral responses to influenza virus and vesicular stomatitis virus. On the basis of the comparison among the antiviral activities associated with many Mx variations, a specific amino acid substitution at position 631 (Ser to Asn) was considered to determine the antivirally positive or negative Mx gene. Thus, a single amino acid substitution influences the antiviral activity of Mx in domesticated chickens.

3T3 Cells↗
PubMed2003

[Hypoglycemic effects of sodium metavanadate in diabetic mice and its effect on glucose phosphorylation].

OBJECTIVE: To investigate the effects of sodium metavanadate (SMV) on blood sugar and glucose phosphorylation in mice, and to discuss the possible mechanism of its hypoglycemic effects. METHODS: Diabetic mice (D) and control mice (V) were randomly allocated to drink SMV (0.2 mg/ml) (CV and DV groups) or NaCl (80 mmol/L) (C and V groups) respectively. The study lasted for 5 weeks. Liver glucokinase, muscle hexokinase, blood glucose and insulin were assayed at the end of each week. RESULTS: Blood glucose was higher in the diabetic groups before the administration of SMV, and the blood glucose level of group DV decreased from (18.77 +/- 1.28) to (8.94 +/- 0.94) mmol/L (P < 0.01) after oral administration of SMV for one week. While liver glucokinase increased from (1.29 +/- 0.64) to (15.36 +/- 1.57) mIU/min/mg protein and muscle hexokinase increased from (1.93 +/- 0.50) to (18.62 +/- 1.71) mIU/min/mg protein (P < 0.01) respectively. There was no continuous change of these parameters during the later weeks. No significant change of serum insulin was observed in the diabetic mice. There was a remarkable negative correlation of blood glucose level with liver glucokinase and muscle hexokinase levels. CONCLUSION: The hypoglycemic effects of SMV was independent of insulin level. In consideration of the close relations of the activities of liver glucokinase and muscle hexokinase with diabetes, and the improving of impaired glucose phosphorylation in diabetic mice by oral sodium metavanadate, which might be the mechanism of hypoglycemic effects of SMV.

Animals↗
PubMed2002

Susceptibility to cyclosporin A-induced autoimmunity: strain differences in relation to autoregulatory T cells.

Cyclosporin A-induced autoimmunity (CsA-AI), also called autoimmune syngeneic graft-vs-host disease, is a thymus dependent, T cell mediated rodent animal model of disease and is considered to be an experimental model for human scleroderma. Since adoptive transfer of CsA-AI by effector T cells can be prevented by autoregulatory T cells, there may also be a role for dominant tolerance in the resistance of certain rat strains to develop clinical manifest CsA-AI. LEW rats have been reported to be susceptible, whereas BN rats are resistant to CsA-AI. In the present study we first demonstrate that PVG, but not DA rats, are susceptible to CsA-AI and that disease characteristics in PVG rats are comparable to LEW rats in terms of pathogenesis and T cell kinetics, although of more rapid onset and greater severity. Next, we examined whether the relative presence of autoregulatory T-helper cells, i.e. CD25+ and/or CD45RClow CD4 T cells, is increased in resistant BN and DA rats. The results obtained reveal that the genetically determined CD45RChigh/CD45RClow ratio, but not the percentage CD25+ cells, within the CD4 T cell compartment of naïve rats is correlated with resistance to CsA-AI in these rat strains. We conclude that the relative presence of autoregulatory T cells with a CD45RClow T-helper cell phenotype may be a critical determinant in susceptibility to CsA-AI.

Animals↗