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Biomedical subjects

Y Eishi

Publications and source records attributed to Y Eishi.

At least 19 recordsLinked to original sources

PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas.

BACKGROUND AND AIMS: Although it has been reported that intestinal metaplasia implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is unclear which genes are responsible for the formation of pseudopyloric glands and whether they play a role in gastric carcinogenesis. Pancreatic-duodenal homeobox 1 (PDX1) is also a ParaHox gene which contributes to the genesis and development of the pancreas, duodenum, and antrum. To clarify its significance for the formation of pseudopyloric glands and gastric carcinogenesis, we investigated expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa. METHODS: Gastric carcinoma tissues from 95 patients were used for immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC. RESULTS: PDX1 was found to be frequently expressed in pseudopyloric glands and intestinal metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The frequency of PDX1 positive reactivity was higher in differentiated type carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in undifferentiated type (33/52, 63.5%) and T2-4 (30/52, 57.7%) carcinomas. PDX1 and MUC6 double positive expression was observed in carcinomas, respectively, including the corpus, and also correlated with histological type and depth of invasion. In contrast, no link was apparent between PDX1 and MUC5AC double positive reactivity and histological type. CONCLUSION: Our study suggests that PDX1 plays an important role in the development of pseudopyloric glands, and that pseudopyloric glands may reflect a condition associated with gastric carcinogenesis.

Aged↗

Gastric mucosal density of Helicobacter pylori estimated by real-time PCR compared with results of urea breath test and histological grading.

The accuracy of the urea breath test (UBT) and histological grading for estimation of the density of Helicobacter pylori in gastric mucosa is not known. Real-time (TaqMan) PCR was used to estimate the total number of H. pylori genomes in biopsy samples. These values were compared with those obtained by the UBT and the histological grade obtained by the Sydney system. The UBT and endoscopy with antral and corporal biopsies were performed in 88 consecutive untreated patients with dyspepsia. Bacterial culture and the rapid urease test were done with fresh biopsy materials. TaqMan PCR and histological examination were done on serial paraffin sections of the biopsy samples. Of the five methods tested, TaqMan PCR had the highest sensitivity and specificity (both 100%) in the diagnosis of H. pylori infection. The mean density of H. pylori genomes for pairs of biopsy samples from individual patients was compared with the individual values obtained by the UBT; correlation between the results was significant. The density of H. pylori genomes was higher in histological grades 1, 2 and 3 than in grade 0, without significant differences between adjacent grades from 1 to 3. These results suggest that the severity of H. pylori infection of the stomach can be estimated by the UBT and that histopathologists might state whether the organism is present or absent, rather than making a quantitative statement as recommended in the Sydney system.

Biopsy↗

Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated.

BACKGROUND: Glandular atrophy and intestinal metaplasia are precancerous lesions; whether Helicobacter pylori eradication affects these lesions is controversial. OBJECTIVE: To determine whether H. pylori eradication is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year. DESIGN: Single-blind, uncontrolled prospective trial. SETTING: Academic gastroenterology clinic in Japan. PATIENTS: 163 consecutive patients with dyspepsia and H. pylori infection. INTERVENTION: One-week course of a proton-pump inhibitor and antibiotic therapy. MEASUREMENTS: Endoscopic examination with antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15 months after treatment. Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System. RESULTS: In the 115 patients in whom H. pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus and intestinal metaplasia in the antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved in 34 (89%) of 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia at baseline. In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed. CONCLUSION: In the year after successful H. pylori eradication, precancerous lesions improved in most patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori DNA in drinking water in Japan.

Helicobacter pylori has been detected in drinking water in Peru and Sweden, suggesting the possibility of water-borne transmission. To date there have been few reports of H. pylori being detected in water; one was of the ureA gene of H. pylori in wells and springs in rural Japan. We examined water sampled in or near urban areas of Japan for H. pylori DNA by three assays using the polymerase chain reaction (PCR). Near Tokyo, samples were obtained: 10 of tap water, 6 of well water, 10 of river water, and 10 of sea water. Samples were filtered with membranes with 0.05- or 0.22-microm pores, which bacterial cells are caught by. Bacterial nucleic acids were extracted and purified and the PCR was done to amplify adhesin specific for H. pylori and the ureA gene, if present. Real-time PCR that measured the yield in terms of fluorescence was done with primers for 16S rRNA. None of the samples of tap, river, or sea water contained adhesin, ureA or 16S rRNA. None of the 6 samples of well water contained adhesin or ureA, but 2 of the 6 samples contained 16S rRNA. Some of the users of the well had had H. pylori infection in the past. H. pylori DNA was detected in well water and the users had been infected, so water-borne transmission via well water may occur even in towns in Japan.

Adhesins, Bacterial↗

Reduced expression of laminin alpha 3 and alpha 5 chains in non-small cell lung cancers.

The basement membrane is considered to act as a barrier which hinders cancer cells from invading the surrounding stroma. In order to assess changes in essential components during neoplasia in the lung, we immunohistochemically studied distribution patterns of laminins alpha 3 and alpha 5 in 40 adenocarcinomas and 8 squamous cell carcinomas. The a 5 chain was generally preserved at the periphery, frequently disrupted in foci with alveolar collapse and absent in foci of fibroblastic proliferation within adenocarcinomas. Fragmentation and absence of laminin alpha 3 chain were more prominent than for alpha 5 chain. Laminin alpha 3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from alpha 5 chain. Non-small cell lung cancers with reduced alpha 5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin alpha 3 and alpha 5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express alpha 3 chain and expression of alpha 5 chain was reduced in three. Quantitative RT-PCR analysis also demonstrated expression of laminin alpha 3 chain in adenocarcinoma tissues to be significantly lower than in normal lung tissues. These results suggest that expression of laminin alpha chains is often reduced in lung cancer cells and this might contribute to basement membrane fragmentation and subsequent proliferation of stromal elements, as well as play some role in the process of cancer cell invasion.

Adenocarcinoma↗

The effects of allopurinol on immune function in normal BALB/c and SCID mice.

To clarify the relationship between purine metabolism and immunity, the in vivo immunosuppressive effects of allopurinol (AL), a xanthinoxidase (XO) inhibitor, were studied using normal BALB/c and severe combined immunodeficient (SCID) mice. Following AL administration for 14 weeks (long term), a decreased immune response to ovalbumin (OVA) in the peripheral blood was observed in normal mice, which might not be only due to direct B cell suppression but also due to suppression of helper T cell function. In the SCID mice, there was a markedly late and reduced recovery of surface immunoglobulin (sIg) positive cells, which are markers for mature B lymphocytes, in the peripheral blood after AL administration. The total immunoglobulin G (IgG) titers in the AL treated group were significantly lower than in the control group 6 weeks after stem cell transfer, but increased until there was no difference in the titers between the two groups at week 14. CD4 positive helper T cells and CD8 positive T cells were slow to recover, though these gradually recovered to reach normal levels in the mature stage. These data suggest that the administration of AL may modulate B cell and T cell responses in OVA-immunized antibody formation. Furthermore, this study showed that AL could influence immune functions during the pre-natal and developmental periods and that its effects might differ according to the stages of maturity of the immune cells.

Allopurinol↗

Endoscopic and histological comparison of nonulcer dyspepsia with and without Helicobacter pylori infection evaluated by the modified Sydney system.

OBJECTIVE: Our aim was to identify endoscopic features associated with Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: A total of 50 infected patients with nonulcer dyspepsia who underwent endoscopy with antral and corporal biopsies and 50 patients matched for age and sex but with nonulcer dyspepsia without H. pylori were reviewed retrospectively by three endoscopists blinded to the H. pylori status and the patient's history. The endoscopic findings of gastritis, classified by a modification of the Sydney system as present or absent, were evaluated, and the histological severity was graded by the updated Sydney system. RESULTS: For endoscopic features, the odds ratio was 53.1 (95% confidence interval, 6.8-414.9) for edema, 18.8 (5.8-60.5) for erythema with reddish streaks excluded, 0.0275 (0.0002-0.477) for reddish streaks, 17.4 (0.97-313.7) for friability, 14.2 (5.1-40.0) for exudate, 17.2 (2.2-137.6) for flat erosions, 2.54 (0.81-7.94) for raised erosions, 40.1 (2.3-694.5) for rugal hypertrophy, 19.1 (2.4-151.6) for rugal atrophy, 96.2 (23.4-395.9) for a vascular pattern, 0.125 (0.010-1.06) for bleeding spots, and 21.0 (2.6-166.5) for nodularity. The histological severity of inflammation, neutrophil activity, and atrophy in the antrum and corpus and of metaplasia in the antrum was greater in the infected patients than in the noninfected patients. CONCLUSIONS: Endoscopic features associated with H. pylori were a vascular pattern, edema, rugal hypertrophy, nodularity, rugal atrophy, erythema with reddish streaks excluded, flat erosions, and exudate. These endoscopic features were associated with the histological findings of inflammation, neutrophil activity, atrophy, and metaplasia.

Atrophy↗

Proliferative response of peripheral blood mononuclear cells and levels of antibody to recombinant protein from Propionibacterium acnes DNA expression library in Japanese patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK: The causes of sarcoidosis are unknown. Propionibacterium acnes has been isolated from sarcoid lesions, and many genomes of P. acnes or P. granulosum have been detected in all biopsy samples tested from Japanese patients with sarcoidosis. We searched for protein antigens from propionibacteria that caused immune responses in patients with sarcoidosis but not in subjects without sarcoidosis. METHODS: A lambda gt11 genomic DNA expression library of P. acnes was screened with sera from patients with sarcoidosis. Antibodies to a recombinant protein from the insert recovered by the screening were measured in serum and bronchoalveolar lavage (BAL) fluid from patients with or without sarcoidosis by an immunofluorescence-based method. Peripheral blood mononuclear cells from patients with and without sarcoidosis were used to examine the lymphoproliferative response to the protein. RESULTS: Of 180,000 plaques screened, two clones coded for an identical recombinant protein, termed RP35, were recognized by sera. RP35 was the C-terminal region of P. acnes trigger factor. RP35 caused sarcoidosis specific proliferation of the mononuclear cells from 9 (18%) of the 50 patients with sarcoidosis; in a similar way, purified protein derived from Mycobacterium tuberculosis evoked specific responses in 8 (38%) of 21 patients with tuberculosis. Serum levels of IgG and IgA antibodies to RP35 were high in patients with sarcoidosis and other lung diseases. In BAL fluid levels IgG or IgA antibodies were high in 7 (18%) and 15 (39%), respectively, of 38 patients with sarcoidosis, and in 2 (3%) and 2 (3%), respectively, of 63 patients with other lung diseases. CONCLUSIONS: The RP35 protein from P. acnes causes a cellular immune response in some patients with sarcoidosis but not in subjects without sarcoidosis.

Adult↗

[A study of reduction of NF 2 protein, mRNA and loss of 22 q in sporadic meningiomas].

Neurofibromatosis 2(NF 2) is one of the tumor suppressor genes, and its disorder has been reported in sporadic meningiomas. We investigated some reduction of expression of NF 2 protein and mRNA in 33 sporadic meningiomas, using immunohistochemistry and in situ hybridization, respectively. Seventeen of 33 (51.5%) meningiomas demonstrated significantly reduced or absent NF 2 protein expression. Its mRNA was also reduced or absent in 11 of 24(45.8%) meningiomas, and some statistically significant correlation was shown between reductions of NF 2 protein and its mRNA. Furthermore, we studied about loss of 22 q in 5 meningiomas with fluorescence in situ hybridization. In the cases with reduction of NF 2 protein and/or mRNA, 22 q telomere signals were observed as loss of heterozygosity. On the other hand, in the cases with expression of NF 2 protein and mRNA, 22 q telomere signals were normal. In conclusion, reduction or absence of NF 2 protein and mRNA may play an important role in the tumorigenesis of about half number of sporadic meningiomas.

Chromosomes, Human, Pair 22↗

Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice.

Intestines of mice with colitis caused by dextran sulfate sodium (DSS) contain more Bacteroidaceae cells than untreated controls. We investigated the roles of intestinal bacteria and succinic acid, a by-product of Bacteroidaceae metabolism, in this model of colitis. CBA/J mice were given 3% DSS in water for 14 days. After mice were anesthetized and killed, concentrations of organic acids in stools from the cecum and colon were measured. The resected rectum and colon were washed with sterile saline; some specimens were incubated with imipenem in saline for 1 h to kill bacteria on the surfaces and others were not. Their homogenates were cultured anaerobically and aerobically. Separately, 1 mL of 20 mM succinic acid was infused into the rectum of mice, whose anal verge was glued. Animals were anesthetized and killed the next day. The rectum and colon were examined histologically. Concentrations of succinate were higher everywhere in the colon of mice with colitis than in controls. Mice with colitis had more Bacteroidaceae cells, especially B. caccae, than controls. Mice given succinate enemas had focal erosions of the mucosa and edema of the submucosa. Succinic acid, produced abundantly by members of the family Bacteroidaceae, especially B. caccae, may be the ulcerogenic agent in DSS colitis.

Acetates↗

Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis.

BACKGROUND: The causes of sarcoidosis are not known. The DNA of Mycobacterium tuberculosis has been detected in some sarcoid lesions. In Japan, Propionibacterium acnes has been isolated from such lesions, but whether this indigenous bacterium is related to the disease is unclear. We used PCR to estimate the number of genomes of these bacteria in sarcoid lesions, to identify any link between sarcoidosis and these two bacterial species. METHODS: We examined formalin-fixed and paraffin-embedded sections of biopsy and surgical samples from lymph nodes of 15 patients with sarcoidosis, 15 patients with tuberculosis, and 15 patients with gastric cancer (controls). Quantitative PCR was done to amplify segments of 16 S ribosomal RNA of P. acnes and P. granulosum and of insertion sequence 6110 of M. tuberculosis. PCR products were identified and the quantities of the products were estimated in terms of the fluorescence of oligonucleotide reporter probes. The numbers of bacterial genomes in samples were estimated from standard curves of serially diluted bacterial DNA. FINDINGS: Genomes of M. tuberculosis were found in samples from all 15 patients with tuberculosis, from three patients with sarcoidosis, and in one control sample. Genomes of P. acnes were found in 12 of the 15 patients with sarcoidosis, in two tuberculosis patients, and three controls. The difference in the estimated number of P. acnes genomes between individuals with and without sarcoidosis was similar to that in the number of M. tuberculosis between people with and without tuberculosis. There were 5x10(5) P. acnes genomes in sarcoidosis and 3x10(6) M. tuberculosis genomes in tuberculosis, respectively, on average per microg of total DNA. The three patients with sarcoidosis but without P. acnes all had P. granulosum DNA in their biopsy samples; the number of genomes of the bacterium was 5x10(5). INTERPRETATION: These findings suggest that propionibacteria had resided or proliferated ectopically in the sarcoid lesions, whether there was a connection with the disease or not. Propionibacteria are a more likely cause than mycobacteria of sarcoidosis.

DNA, Bacterial↗

Synthesis of basement membrane by gastrointestinal cancer cell lines.

Gastrointestinal adenocarcinoma-derived cell lines were studied in order to determine their pattern of expression of basement membrane components and their ability to form a basement membrane. In contrast to the well-preserved expression of laminin beta 2, beta 3, gamma 1, and gamma 2 chain mRNAs, five of eight gastrointestinal cancer cells lacked alpha 3 mRNA. Immunohistochemical and electron microscopic examination of four cell lines transplanted subcutaneously to SCID mice demonstrated the presence of both alpha 3 and alpha 5 chains and the formation of a basal lamina in two cases. The other two cell lines lacked both alpha 3 and alpha 5 chains and could not form a basal lamina, suggesting that this deficiency may be a factor which affects their ability to form a basement membrane. This abnormality might play some role in stromal invasion by tumour cells in gastrointestinal cancer.

Animals↗

The influence of initial exposure timing to beta-lactoglobulin on oral tolerance induction.

BACKGROUND: Although a number of studies have investigated the induction of oral tolerance to several proteins, relatively little is known about the induction of oral tolerance to beta-lactoglobulin, one of the major antigenic proteins in milk. OBJECTIVE: We investigated the influence of the timing of the initial beta-lactoglobulin exposure on oral tolerance induction and examined some characteristics of the tolerogenic immune response. METHODS: BALB/c mice were given beta-lactoglobulin prenatally or from the third or fifth postnatal week, bred for 17 weeks, and compared with unexposed control mice. Specific plasma anti-beta-lactoglobulin antibodies (total IgG, IgG subclasses, IgM, and IgE), antigen-specific splenocyte responses, frequencies of antibody-producing cells, and cytokine production by splenocytes, intestinal mucosal lymphocytes, and Peyer's patches were analyzed. RESULTS: Differences were observed among the 4 groups of mice in changes of plasma anti-beta-lactoglobulin antibody titers, antigen-specific T-cell proliferation, and frequencies of antibody-producing splenocytes, intestinal mucosal lymphocytes, and Peyer's patch cells after the first exposure to beta-lactoglobulin. The onset and duration of the immunologic responses were found to be dependent on the timing of antigen exposure. Prenatal exposure to antigen facilitated the induction of oral tolerance to beta-lactoglobulin, whereas delayed antigen exposure retarded tolerance. The induction of oral tolerance was associated with increased IL-4 and/or IL-10 production and decreased IL-12 production. CONCLUSION: Our results suggest that the timing of initial antigen exposure greatly influences the induction of oral tolerance to beta-lactoglobulin and that altered secretion of regulatory cytokines may be responsible for the differences in antibody production and oral tolerance induction.

Administration, Oral↗

Sequence variations of Epstein-Barr virus LMP2A gene in gastric carcinoma in Japan.

The latent EBV gene products expressed in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), are only LMP2A, EBNA-1, BARF-0 and EBERs. To examine the correlation between LMP2A sequence variation in EBVaGC and transformation of the cells, the complete sequence of the LMP2A gene was determined in three cases of Japanese EBVaGC and compared with the prototype B95-8 strain. In addition, the sequences of exons 2,6 and 7 of LMP2A were determined in four to six EBVaGC cases. The results of sequence analysis indicated that LMP2A of EBVaGC was structurally very similar to B95-8, but contained a significant nucleotide variation. Ten nucleotide substitutions were identified in almost all cases tested, and three of these caused amino acid changes. Of these three, two amino acid substitutions were not expected to change any known functions of LMP2A. The other amino acid substitution from serine to threonine was located at codon 348 within one of the target epitopes of EBV-specific cytotoxic T-lymphocytes. The LMP2A of EBV in peripheral blood lymphocytes from six healthy individuals showed serine (4/6 cases) or threonine (2/6 cases) substitution at codon 348, while LMP2A with the threonine substitution was the major form (5/6 cases) observed in EBVaGC, indicating that EBV with the threonine substitution may confer an advantage for viral persistence in tumor cells. However, our sequencing results suggested that the LMP2A protein in EBVaGC is functionally similar to that of the B95-8 strain and is not unique to gastric carcinoma, indicating the importance of LMP2A for EBV latency.

Amino Acids↗

Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal squamous cell carcinomas.

Using oesophageal squamous cell carcinoma samples of both intramucosal and advanced types, proliferative activity (Ki-67 labelling index), p53 protein accumulation and apoptosis (in situ DNA nick end labelling) were assessed, and the relation of these values to progression or differentiation grade of tumours was analysed. In terms of proliferative activity and the proportion of positive cases with p53 accumulation, a statistically significant difference was demonstrated between intraepithelial carcinomas and intramucosal carcinomas with stromal invasion (17.2% vs 31.7% for the Ki-67 labelling index, and 23.5% vs 67.4% for the proportion of positive cases of p53 accumulation). Values for the latter were almost comparable to those of advanced carcinomas. Immunohistologically, Ki-67 positive, proliferating cells were distributed preferentially in the peripheral fronts of invading nests. Apoptotic cells were observed in the inner areas of the invading nests of the intramucosal carcinomas with stromal invasion and in more advanced lesions, but were rarely observed in the normal epithelium or intraepithelial carcinomas. Apoptotic cells were seen mainly around areas of keratinization, and the apoptotic cell index was higher in well and moderately differentiated types of advanced carcinomas than in the poorly differentiated type (2.59% vs 1.09%). An increase in proliferative activity and an accumulation of p53 protein are associated with the onset of early carcinomatous invasion, while apoptosis is closely linked with the differentiation grade of carcinoma cells.

Antibodies, Monoclonal↗

Expression of the cyclin dependent kinase inhibitor p21WAF1/CIP1 in oesophageal squamous cell carcinomas.

To elucidate the role of CDK inhibitor p21WAF1/CIP1 in human oesophageal squamous cell carcinomas, we examined its expression immunohistochemically using surgically resected tissues from 25 patients, and have analyzed the relationship with alteration of p53 gene (F-SSCP analysis), proliferative activity (Ki-67 labelling index), frequency of apoptosis (in situ DNA nick end labelling), and degree of differentiation. P21 expression was observed in 11 cases (44%) with a percentage of positive cells ranging between 1% and 10%. Of the 25 cases, 4 cases showed > 5% of positive cells. As for the relationship with p53 gene, all 7 p53-mutation positive cases were negative for p21 expression, whereas 11 out of 18 mutation negative cases showed positive for p21 expression. As for the relationship with degree of tumour differentiation, 6 out of 8 well differentiated type cases showed positive for p21 expression. By contrast, all 8 cases of poorly differentiated type were negative for p21 expression. Frequency of apoptotic cells was significantly higher in p21 positive cases than negative cases although Ki-67 labelling index was almost the same regardless of the expression of p21. P21 expressing cells were distributed mainly in the middle layers of the invading nests, especially around the keratinization, which was almost similar to the distribution of apoptotic cells. Our results suggest that expression of p21 in human oesophageal squamous cell carcinomas is induced by a p53-dependent pathway and affects apoptosis and differentiation of carcinoma cells.

Adult↗

Suppression of mitogen-induced IL-2R alpha expression in PBL by serum from microfilaraemic rats chronically infected with Brugia pahangi.

To study immunological responses in filarial infections, interleukin-2 receptor alpha (IL-2R alpha) expression in the peripheral blood lymphocytes (PBL) of Lewis rats infected with Brugia pahangi was observed by flow cytometry. During infection, no increase in IL-2R alpha was observed in either microfilaraemic or amicrofilaraemic rats. The PBL of rats were stimulated with phytohaemagglutinin (PHA) and the frequency of IL-2R alpha-positivity was examined. After microfilariae appeared, the increase in the rate of IL-2R alpha-positivity in microfilaraemic rats was less than in amicrofilaraemic rats. The anergy of IL-2R alpha expression in microfilaraemic rats was restored when their lymphocytes were cultured with normal rat serum. IL-2R alpha expression in normal uninfected rats decreased when cultured with serum from microfilaraemic rats. These results suggest that microfilariae-related factors in rat serum suppress PHA-induced IL-2R alpha expression in PBL and thus inhibit cell proliferation and host immunity.

Animals↗