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Biomedical subjects

M Miyake

Publications and source records attributed to M Miyake.

At least 145 records · Page 8Linked to original sources
PubMed1998

Long-term alcohol effects on hepatic phosphoglucomutase activities in relation to posttranslational modification of the protein.

ADP-ribosylation is a posttranslational protein modification catalyzed by two classes of enzymes: mono-ADP-ribosyltransferase and poly-ADP-ribose polymerases. We previously demonstrated that long-term alcohol intake remarkably enhanced an endogenous ADP-ribosylation of a 58 kDa protein in rat liver and also identified the 58 kDa protein as phosphoglucomutase (PGM). To assess biological significance of this phenomenon, we tested the effects of long-term alcohol intake on PGM activities in connection with posttranslational modification of the protein. ADP-ribosylation of PGM was mono- rather than poly-ADP-ribosylation. Also, nonenzymatic binding of ADP-ribose was excluded. It was of note that ADP-ribosylation of exogenous PGM was remarkably increased by adding rat liver plasma membranes, and that the extent of the increase was greater in alcohol-fed rats than in pair-fed controls. Furthermore, PGM activities were significantly increased after long-term alcohol intake concomitant with increased ADP-ribosyltransferase activities toward PGM. In view of the variety of roles of PGM in the liver, such as carbohydrate metabolism and Ca2+ homeostasis, it is tempting to speculate that increased ADP-ribosylation of PGM may play a role in long-term alcohol effects on hepatocytes.

ADP Ribose Transferases↗
PubMed1998

Growth inhibition, enhancement of intercellular adhesion, and increased expression of carcinoembryonic antigen by overexpression of phosphoinositides-specific phospholipase C beta 1 in LS174T human colon adenocarcinoma cell line.

By using a retrovirus-derived system we generated derivatives of the human colon adenocarcinoma cell line LS174T (ATCC CL 188) that stably overexpress a full-length cDNA encoding the beta 1 isoform of bovine phosphoinositides-specific phospholipase C (PI-PLC). This was confirmed by the elevated levels of catalytic activity to release phosphoinositides from phosphatidylinositol (PI-PLC) or phosphatidylinositol-bis-phosphate (PIP2-PLC), and the enhanced expressions of messenger RNA and protein. PI-PLC beta 1 overexpresser clones grew to form cell clumps floating in liquid medium, whereas the pMV7-introduced control clones displayed morphologic characteristics that were very similar to those of the parent LS174T cell line. Three individual PI-PLC beta 1 overexpresser cell lines displayed increased doubling time (18.0 h, 21.5 h, and 23.8 h) when compared with 4 individual pMV7-introduced control cell lines (13.1 h, 10.7 h, 12.9 h, and 9.3 h). Anchorage-independent growth ability in soft agar medium was dramatically suppressed by overexpression of PLC beta 1, and the ability of PLC-overproducer clones to form aggregates when cultured in liquid medium was dramatically enhanced when compared with that of pMV7-introduced control clones. Tumorigenicity of PLC beta 1-overproducers was much weaker than that of vector-transduced control clones. The spontaneous release of carcinoembryonic antigen from PLC beta 1-overproducer clones was much higher than that from pMV7 control clones. The ability of PLC beta 1-overproducer clones to form aggregates during suspension culture was much stronger than that of the control clones. These results provide the first evidence that elevated levels of endogenous PI-PLC beta 1 suppress tumor cell growth, but enhance the ability to form cell aggregates and to release carcinoembryonic antigen, an intercellular adhesion molecule.

Adenocarcinoma↗
PubMed1998

Prevalence of hepatitis B and C virus markers in outpatients of Mongolian general hospitals.

In East Asian countries, the prevalence of viral hepatitis has been reported to be high, but precise data for each country remained to be investigated. Here we report the prevalence of viral markers of hepatitis B and hepatitis C in outpatient volunteers visiting two general hospitals in Ulaanbaatar, Mongolia. One hundred fifty sera were tested for HBs antigen (HBsAg), anti-HBs, and anti-HCV by Counting Immunoassay. The backgrounds of groups of patients positive for HBsAg and negative for anti-HCV (group 1; n = 18), negative for HBsAg and positive for anti-HCV (group 2; n = 47), positive for both HBsAg and anti-HCV (group 3; n = 25), and negative for both HBsAg and anti-HCV (group 4; n = 60) were compared. The prevalence of HBsAg, anti-HBs, and anti-HCV in this study group was 28.7%, 39.3% and 48.0%, respectively. Subjects of group 1 (mean +/- SD; 31.3 +/- 12.4 years old) were younger than those of group 4 (39.2 +/- 14.3; p < 0.05), while patients of group 2 (48.7 +/- 15.5) were older than those of group 4 (p < 0.01). More group 2 subjects had histories of jaundice (23/47) than those of group 4 (15/60; p < 0.05). Transaminase levels were higher in group 1 (median (range) IU/l of AST, ALT; 29 (13-95), 32 (9-144) and group 3 (25 (15-187), 22 (8-185)) than in group 4 (18 (9-13), 15 (6-133); p < 0.05, p < 0.005 vs. group 1, and p < 0.005, p < 0.001 vs. group 3, respectively). In HBsAg-negative subjects, those with higher titers of anti-HCV (cut-off index > 15) were older, and had more histories of jaundice and higher levels of AST and ALT than anti-HCV negative subjects (50.3 +/- 14.8 vs. 39.1 +/- 14.3, p < 0.01; 15/28 vs. 15/60, p < 0.01; 22.5 (12-127) vs. 18 (9-93), p < 0.05; 20.5 (7-362) vs. 15 (6-133), p < 0.05; respectively). In conclusion, this preliminary surveillance for hepatitis B and C viral markers showed that both hepatitis viruses are prevalent and may cause liver diseases in Mongolia. A nation-wide survey for these viruses should be urged and preventive measures should be taken to suppress the spread and development of liver diseases in this country.

Adult↗
PubMed1998

Distribution of Staphylococcus species among human clinical specimens and emended description of Staphylococcus caprae.

By DNA-DNA hybridization on microplates, we identified 1,230 strains of staphylococci from human clinical specimens and determined the distribution of species. The 10 Staphylococcus species isolated most often were S. epidermidis (31.3%), S. aureus (23.3%), S. haemolyticus (12.2%), S. caprae (10.7%), S. simulans (4.4%), S. hominis (4.0%), S. capitis (3.9%), S. saprophyticus (3.6%), S. warneri (2.2%), and S. lugdunensis (1.3%). From these results, we realized that S. caprae strains were widely distributed in human clinical specimens. The description in Bergey's Manual of Systematic Bacteriology indicates that no strains of S. caprae produce acid from fructose and mannitol, but all our S. caprae strains produced acid from fructose and mannitol. Consequently, many strains of S. caprae isolated from human clinical specimens have been misidentified as S. haemolyticus or S. hominis by conventional biochemical tests. In this paper, we propose an emended description of S. caprae.

Bacterial Typing Techniques↗
PubMed1998

Reduced integrin alpha3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung.

PURPOSE: We investigated the possible association between integrin alpha3 and motility-related protein (MRP-1), cluster of differentiation antigen 9 (CD9) gene expression in non-small-cell lung cancer (NSCLC) and evaluated the prognostic significance of integrin alpha3 expression. PATIENTS AND METHODS: We performed a retrospective study of integrin alpha3 and MRP-1/CD9 expression in resected tumor tissues from 151 NSCLC patients using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The ratio of integrin alpha3/beta-actin expression ranged from 0 to 5.87 (mean was 0.80; median, 0.70). Using the cutoff value of 0.7, there were 78 (52%) integrin alpha3-positive tumors and 73 (48%) tumors with reduced integrin alpha3 expression. The immunohistochemical results agreed well with those of the RT-PCR assays, and 88% had no discrepancy. In case of discrepancy, the results of RT-PCR were used in specimen classification. Integrin alpha3 gene expression was independent from MRP-1/CD9 gene expression. No significant association was found between integrin alpha3 expression and the patients' clinical characteristics. The overall survival rate of patients with integrin alpha3-positive NSCLCs was only slightly better than that of individuals whose tumors had reduced integrin alpha3 expression (55.9% v 47.1%; P = .085). By comparison, the overall survival rate of patients with integrin alpha3-positive adenocarcinomas was strikingly greater than in those whose tumors had reduced gene expression (54.4% v 35.2%; P = .004). Multivariate analysis with the Cox regression model of NSCLC and adenocarcinoma indicated that integrin alpha3 expression correlated better (P = .0188 and P = .0008, respectively) with the overall survival rate than other variables, except lymph node status. CONCLUSION: No significant association was found between integrin alpha3 and MRP-1/CD9 gene expression in lung cancer. However, reduced integrin alpha3 expression is a poor prognosis factor in patients with adenocarcinomas.

Adenocarcinoma↗
PubMed1998

Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression.

PURPOSE: The transmembrane-4 superfamily (TM4SF) is a recently discovered family of genes. Of the TM4SF members, MRP-1/CD9, KAI1/CD82, and ME491/CD63 have been reported to modulate tumor progression or metastasis. In this study, we investigated the relationships between these three genes, MRP-1, KAI1, and ME491, in patients with non-small-cell lung cancers (NSCLCs). Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs. PATIENTS AND METHODS: One hundred seventy-two patients up to stage IIIB NSCLC underwent radical surgery during the period of January 1991 through June 1994. Using a quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we studied the expression of MRP-1, KAI1, and ME491 genes in these patients. RESULTS: We found that 109 patients (63.4%) had MRP-1-positive tumors and 42 patients (24.4%) had KAl1-positive tumors. Conversely, all 172 patients expressed ME491. No relationship was found between MRP-1 expression and KAI1 expression. We classified these patients into three groups. The 36 patients who were positive for both MRP-1 and KAI1 were defined as group A; the 79 patients with reduced expression of either MRP-1 or KAI1 were defined as group B, and the remaining 57 patients with reduced expression of both MRP-1 and KAI1 were defined as group C. This new classification was correlated with nodal status, tumor status, and pathologic stage (P = .0056, P = .0003, and P < .0001, respectively). In NSCLC patients, the 5-year survival rate of group A patients was significantly better than that of group B patients and much better than that of group C patients (86.8%, 53.9%, and 31.5%, respectively; P < .0001). Cox multivariate regression analysis showed that this new classification in NSCLCs was a significant prognostic factor, as was the nodal status (P < .0001). CONCLUSION: Our results suggest that a low MRP-1 and KAI1 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that the evaluation for MRP-1 and KAI1 expression may identify node-negative lung cancer patients who are at high risk for early disease recurrence, and thus need intensive adjuvant therapy.

Adult↗
PubMed1998

Enhancement of the vanadate-stimulated release of lipoprotein lipase activity by astilbin from the leaves of Engelhardtia chrysolepis.

Astilbin, a dihydroflavonol rhamnoside isolated from the leaves of Engelhardtia chrysolepis, enhanced the vanadate-stimulated release of lipoprotein lipase (LPL) activity from rat isolated fat pads. N-[2-(Methyl-amino)ethyl]-5-isoquinolinesulfonamide (H-8), a potent inhibitor of cAMP-dependent protein kinase (PKA), markedly inhibited the enhancement by astilbin. Lipolysis in the fat pads was stimulated by astilbin alone in a dose-dependent manner and this stimulation was suppressed in the presence of vanadate, probably due to its antilipolytic action. A significant enhancement by astilbin was observed with increasing effects of vanadate on cAMP content in the fat pads and on cAMP phosphodiesterase (PDE) activity in the particulate fraction although astilbin alone showed only a slight increase in the cellular cAMP content and PDE activity. Astilbin may enhance the vanadate-stimulated release of LPL activity through a synergistic effect on an increase in the cellular cAMP content produced by vanadate accompanied by more potent activation of PKA.

Adipose Tissue↗
PubMed1998

Mutations of p53 and K-ras genes as prognostic factors for non-small cell lung cancer.

To evaluate the importance of mutations of p53 and K-ras genes in the prognosis of patients with non-small cell lung cancer, one hundred and forty-four patients who underwent surgery were studied. DNA was extracted from frozen specimens. Polymerase chain reaction-single strand conformation polymorphism and sequencing were performed to investigate mutations of p53 from exon 5 to 8, and mutations of exon 1 of K-ras. Mutations of p53 gene occurred in 35. 4% of patients, and mutations of the K-ras gene in 8.3%. The overall survival rate of non-small cell lung cancer patients with wild-type K-ras was better than that of patients whose tumors had mutations of K-ras (P=0.0330). Among patients with adenocarcinoma of the lung, the overall survival rate of patients with wild-type p53 was strikingly better than that of patients whose tumors had mutations of p53 (P=0.0234). Multivariate analysis with the Cox regression model of all patients with non-small cell lung cancer and those with adenocarcinoma indicated that mutations of K-ras best correlated with the overall survival rate (P=0.0005 and P=0.0361, respectively). In conclusion, evaluation of mutations of both the p53 and K-ras genes in the lung tumors might be useful for assessing the prognosis, especially in patients with adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Therapy-related leukemia and myelodysplasia following oral administration of etoposide for recurrent breast cancer.

We report a high risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of etoposide for recurrent breast cancer. We examined 119 patients with recurrent disease. Patients were initially treated with anthracyclines, cyclophosphamide, or cisplatin with or without radiation before etoposide treatment. Etoposide was used as the final drug in most cases. Twenty-four patients were treated with the oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to etoposide. In contrast, the development of t-AML/MDS was not observed in the other 95 patients not treated with etoposide. Our data suggest that there is a substantial risk of secondary leukemia with oral administration of etoposide for a prolonged period as well as i.v. schedules.

Administration, Oral↗
PubMed1998

Correlation of prognosis of breast cancer patients and expression of Ley which acts as a cofactor of tumor procoagulant.

Association between Ley expression and prognosis of breast cancer was investigated using monoclonal antibody (MoAb) FS01, which recognizes Ley as an epitope, inhibits the procoagulant activity of cancer cell-derived coagulating activity 1 (CCA-1). Expression intensity and procoagulant activity of CCA-1, tissue factor and HLA-DR on breast cancer cell lines were also examined. Immunohistochemical staining of Ley was performed on primary lesions of 223 breast cancer patients who received absolute curative operation. Flow cytometric analysis and clot timer was used to detect expression and activity of each procoagulant on cancer cell lines. The Ley expression was 73.5%, and no significant relation was observed between clinicopathological factors and intensity of Ley expression. The group showing strong Ley positivity had a significantly poorer prognosis than the Ley-negative group in 5-year disease-free survival (p=0.019). Multivariate analysis using the Cox's proportional hazards' regression model showed that Ley expression is an independent prognostic factor (p=0.018), following tumor size and lymph node metastasis. Ley expression on cancer cell surface is higher than tissue factor and HLA-DR. FS01 and anti-tissue factor MoAb inhibited the coagulating activity of tissue factor-expressing lines, but no cells were inhibited by staphylococcal enterotoxin A, which is known to inhibit the coagulating activity of HLA-DR. CCA-1 and tissue factor plays a important role in the blood coagulating activity of breast cancer cell lines. Breast cancer patients are thought to have a poor prognosis because Ley expression on the surface of the cancer cell induces blood coagulation via CCA-1.

Aged↗
PubMed1998

Histological analysis of the aortic nerve in the rat raised in space (Rapid communication on Neurolab Project).

To study development of the aortic nerve baroreflex under conditions of microgravity, we examined the cross section of the left aortic nerve (LAN), which is the afferent of the baroreflex, in the neonate rats aged 25 days raised in microgravity on the space shuttle Columbia (flight:FLT group) for 16 days. In this paper, we report a part of the result obtained from the data of the myelinated fibers of LAN analyzed with an electron microscope. Two kind of ground control groups were compared to the FLT group; one was asynchronous ground control (AGC) group where the rats were housed in the same cage as that on the shuttle, and the other was vivarium(VIV) group where the rats were housed in a commercial cage. The LANs in each group were extirpated the from rats perfused with a fixative and embedded for histological analysis. We observed the transverse sections of LAN and took pictures of several areas (magnified to x 2K to x 200K). No irregular myelination was found in all fibers of FLT group when they were compared with two control groups. The thickness of myelin of the maximally myelinated fibers were 0.55 +/- 0.17 micrometer in FLT(n=5), 0.45 +/- 0.10 micrometer in AGC(n=5), and O.47 +/- 0.06 micrometer meter in VIV(n=5). There was no significant difference among three groups (unpared t-test). The results suggest that there is no effect of space environment on the myelin formation of each nerve fiber in the aortic nerve.

Animals↗
PubMed1998

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Bovine oocytes from early antral follicles grow to meiotic competence in vitro: effect of FSH and hypoxanthine.

A large number of oocytes are contained in the mammalian ovary. A very small number of these oocytes grow to the final size, mature, and are ovulated. In the ovary there are more early antral follicles than late antral or preovulatory follicles, offering a large pool of oocytes for IVM and IVF if appropriate culture conditions could be devised. In the present study, early antral follicles containing oocytes 90 to 99 microm in diameter were isolated from bovine ovaries. Cumulus-oocyte complexes (COC) with pieces of parietal granulosa (COCG) were then dissected from the follicles. The COCGs were embedded in collagen gels and cultured in Medium 199 with 10% fetal calf serum (FCS) for 8 d. In Experiment 1, the effect of hypoxanthine and FSH on the growth of bovine oocytes was examined. When hypoxanthine (2 and 4 mM) and FSH (10 ng/ml) were added to the culture medium, the number of granulosa cell-enclosed oocytes increased significantly (P < 0.05). All of the oocytes surrounded by granulosa cells showed a normal morphology and were at the germinal vesicle stage, while 75 to 94% of the denuded oocytes were degenerated and had resumed meiosis. The mean diameter of the oocytes showing normal morphology was significantly higher than that measured before culture (P < 0.05). In Experiment 2, the maturational competence of in vitro-grown bovine oocytes was examined. Oocytes which were 90 to 99 microm in diameter before culture did not have meiotic competence. After being in a growth culture of 4 mM hypoxanthine- and 10 ng/ml FSH-supplemented medium for 7 or 11 d, granulosa cell-enclosed oocytes were recovered from the COCGs. No significant difference (P < 0.05) in the diameters of the oocytes was observed between 7 and 11 d of culture (7 d: 107.5 +/- 6.1 microm, n = 30; 11 d: 108.0 +/- 5.3 microm, n = 35). After a subsequent 24 h in a maturation free of hypoxanthine and FSH medium, only 17% of the oocytes cultured for 7 d underwent germinal vesicle breakdown. On the other hand, 89% of the oocytes cultured for 11 d underwent germinal vesicle breakdown, and 11% of the oocytes emitted the first polar body and reached metaphase II. These results demonstrate for the first time that bovine oocytes harvested from early antral follicles can grow, and acquire meiotic competence in vitro.

Journal Article↗
PubMed1997

Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis.

Motility-related protein-1 (MRP-1)/CD9 is a trans-membrane glycoprotein closely associated with suppression of cell motility and reduced metastatic potential of some tumor cells. We currently report that, according to the RT-PCR method for MRP-1/CD9 gene expression, patients with low expression of MRP-1/CD9 in non-small-cell lung cancer, especially the adenocarcinoma type, showed short overall survival. Then, to determine accurately the prognostic value of MRP-1/CD9 product levels in lung-adenocarcinoma cells, we immunohistochemically investigated its expression in 132 lung-adenocarcinoma patients undergoing potentially curative surgery. Of these patients, 44 (33%) showed reduced expression of MRP-1/CD9 in cancer cells, and an inverse association was observed between its expression and factors associated with tumor progression, such as nodal involvement (p = 0.029) or stage (p = 0.028). Patients with reduced expression of MRP-1/CD9 showed a significantly worse prognosis in overall survival (p = 0.005) and disease-free survival (DFS; p < 0.0001) than those with stronger expression; and even among patients with stage-I disease, similar results were obtained (overall survival, p = 0.038; DFS, p = 0.012). In a multivariate analysis, immunohistochemical MRP-1/CD9-expression level was an independent prognostic factor for DFS (p = 0.021), but not for overall survival (p = 0.572). Thus, immunohistochemical MRP-1/CD9-expression level solely in lung-adenocarcinoma cells within the tumor tissue appears to be a prognostic factor for DFS, and may be useful for detecting a high-risk sub-group of recurrence during the post-operative clinical course of the disease.

Adult↗
PubMed1997

YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region on 9q31.

Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. We had mapped the FCMD gene to an approximately 5-cM interval between D9S127 and D9S2111 on 9q31-q33 and had also found evidence for linkage disequilibrium between FCMD and D9S306 in this candidate region. Through further analysis, we have defined another marker, D9S172, which showed stronger linkage disequilibrium than D9S306. A yeast artificial chromosome (YAC) contig spanning 3,5 Mb, which includes this D9S306-D9S172 interval on 9q31, has been constructed by a combination of sequence-tagged site, Alu-PCR, and restriction mapping. Also, cosmid clones subcloned from the YAC were assembled into three contigs, one of which contains D9S2107, which showed the strongest linkage disequilibrium with FCMD. These contigs also allowed us to order the markers as follows: cen-D9S127-(approximately 800 kb)-D9S306 (identical to D9S53)-(approximately 700 kb)-A107XF9-(approximately 500 kb)-D9S172-(approximately 30 kb)-D9S299 (identical to D9S774)-(approximately 120 kb)-WI2269-tel. Thus, we have constructed the first high-resolution physical map of the FCMD candidate region. The YAC and cosmid contigs established here will be a crucial resource for identification of the FCMD gene and other genes in this region.

Chromosomes, Artificial, Yeast↗
PubMed1997

Survival of Vi-capsulated and Vi-deleted Salmonella typhi strains in cultured macrophage expressing different levels of CD14 antigen.

We examined the intracellular survival of Vi-capsulated (lipopolysaccharide; (LPS)-masked) and Vi-deleted (LPS-exposed) Salmonella typhi strains inside macrophage cell lines. Growth of LPS-exposed S. typhi was inhibited in both mouse and human macrophage cell lines. However, the LPS-exposed strain survived in a CD14-deficient mouse macrophage cell lines. Wild-type S. typhi strain, which expressed the Vi antigen and masked LPS, survived in the resting human macrophage cell line. When the Vi-capsulated S. typhi entered the cells, the production of tumor necrosis factor-alpha (TNF-alpha) was suppressed. In contrast, S. typhimurium and LPS-exposed S. typhi stimulated the macrophages to produce a high level of TNF-alpha.

Animals↗