Biomedical subjects

S Sun

Publications and source records attributed to S Sun.

At least 127 records · Page 7Linked to original sources

PubMed1999

Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor.

Cyclin D3 plays a major role in the development of polyploidy in megakaryocytes. The expression of cyclin D3 gene and the level of cyclin D3 protein are increased by the Mpl ligand in the Y10/L8057 megakaryocytic cell line, as indicated by Northern and Western blot analyses, and by nuclear run-on assays and transfection experiments with cyclin D3 promoter constructs. DNase I footprinting of the promoter region showed protected segments, at -75 to -60 bp and at -134 to -92 bp, which display binding sites for the Sp family of transcription factors. Gel mobility shift assay and supershifts with specific antibodies indicate that Sp1 binds to these regions in the cyclin D3 promoter and that Sp1 binding activity is significantly increased by Mpl ligand. Mutation of either Sp1 site both decreases the basal promoter activity and eliminates the induction by Mpl ligand. We find that the nonphosphorylated form of SP1 has greater affinity for the cyclin D3 promoter and that the majority of Sp1 in the cells is nonphosphorylated. Mpl ligand treatment results in increased levels of Sp1 protein, which also appears as nonphosphorylated. Okadaic acid, which inhibits protein phosphatase 1 (PP1) and shifts Sp1 to a phosphorylated form, decreases cyclin D3 gene expression and suppresses Mpl ligand induction. Our data point to the potential of Mpl ligand to activate at once several Sp1-dependent genes during megakaryopoiesis.

Animals↗

PubMed1999

Protein-energy undernutrition among elderly hospitalized patients: a prospective study.

CONTEXT: Numerous studies have identified strong correlations between the severity of nutritional deficits and an increased risk of subsequent morbid events among the hospitalized elderly, but whether inadequate nutrient intake during hospitalization contributes to such nutritional deficits or the risk of adverse outcomes is not known. OBJECTIVES: To identify the distribution of average daily nutrient intake among the nonterminally ill hospitalized elderly, ascertain what factors contribute to persistently low intakes, and determine whether the adequacy of nutrient intake correlates with the risk of mortality. DESIGN: Prospective cohort study conducted from 1994 to 1997. SETTING: University-affiliated Department of Veterans Affairs hospital. PATIENTS: A total of 497 patients 65 years or older (mean [SD] age, 74 [6] years; 97% male; 86% white) with a length of stay of 4 days or more. MAIN OUTCOME MEASURES: Daily in-hospital nutrient intake, in-hospital mortality, and 90-day mortality. RESULTS: A total of 102 patients (21%) had an average daily in-hospital nutrient intake of less than 50% of their calculated maintenance energy requirements. Admission illness severity, average length of stay, and admission albumin and prealbumin levels for this low nutrient group did not differ significantly from those of the remaining patients. However, the low nutrient group had lower mean (SD) discharge serum total cholesterol (154 [44] mg/dL [4 [1.1] mmol/L] vs 173 [42] mg/dL [4.5 [1.1] mmol/L]; P=.001), albumin (29.1 [6.7] vs 33.2 [6.1] g/L, P=.001), and prealbumin (162 [69] vs 205 [68] mg/L; P=.001) concentrations and a higher rate of in-hospital mortality (relative risk, 8.0; 95% confidence interval, 2.8-22.6) and 90-day mortality (relative risk, 2.9; 95% confidence interval, 1.4-6.1). Contributing to the problem of inadequate nutrient intake, patients were frequently ordered to have nothing by mouth and were not fed by another route. Neither canned supplements nor nutritional support were used effectively. CONCLUSIONS: Throughout their hospitalization, many elderly patients were maintained on nutrient intakes far less than their estimated maintenance energy requirements, which may contribute to an increased risk of mortality. Given the difficulties reversing established nutritional deficits in the elderly, greater efforts should be made to prevent the development of such deficits during hospitalization.

Aged↗

PubMed1999

Evidence for a two-base mechanism involving tyrosine-265 from arginine-219 mutants of alanine racemase.

A positively charged residue, R219, was found to interact with the pyridine nitrogen of pyridoxal phosphate in the structure of alanine racemase from Bacillus stearothermophilus [Shaw et al. (1997) Biochemistry 36, 1329-1342]. Three site-directed mutants, R219K, R219A, and R219E, have been characterized and compared to the wild type enzyme (WT) to investigate the role of R219 in catalysis. The R219K mutation is functionally conservative, retaining approximately 25% of the WT activity. The R219A and R219E mutations decrease enzyme activity by approximately 100- and 1000-fold, respectively. These results demonstrate that a positively charged residue at this position is required for efficient catalysis. R219 and Y265 are connected through H166 via hydrogen bonds. The R219 mutants exhibit similar kinetic isotope effect trends: increased primary isotope effects (1.5-2-fold) but unchanged solvent isotope effects in the L --> D direction and increased solvent isotope effects (1.5-2-fold) but unchanged primary isotope effects in the D --> L direction. These results support a two-base racemization mechanism involving Y265 and K39. They additionally suggest that Y265 is selectively perturbed by R219 mutations through the H166 hydrogen-bond network. pH profiles show a large pKa shift from 7.1-7.4 (WT and R219K) to 9. 5-10.4 (R219A and R219E) for kcat/KM, and from 7.3 to 9.9-10.4 for kcat. The group responsible for this ionization is likely to be the phenolic hydroxyl of Y265, whose pKa is electrostatically perturbed in the WT by the H166-mediated interaction with R219. Accumulation of an absorbance band at 510 nm, indicative of a quinonoid intermediate, only in the D --> L direction with R219E provides additional evidence for a two-base mechanism involving Y265.

Alanine Racemase↗

PubMed1999

Structures of normal single-stranded DNA and deoxyribo-3'-S-phosphorothiolates bound to the 3'-5' exonucleolytic active site of DNA polymerase I from Escherichia coli.

The interaction of a divalent metal ion with a leaving 3' oxygen is a central component of several proposed mechanisms of phosphoryl transfer. In support of this are recent kinetic studies showing that thiophilic metal ions (e.g., Mn2+) stimulate the hydrolysis of compounds in which sulfur takes the place of the leaving oxygen. To examine the structural basis of this phenomenon, we have solved four crystal structures of single-stranded DNA's containing either oxygen or sulfur at a 3'-bridging position bound in conjunction with various metal ions at the 3'-5' exonucleolytic active site of the Klenow fragment (KF) of DNA polymerase I from Escherichia coli. Two structures of normal ssDNA bound to KF in the presence of Zn2+ and Mn2+ or Zn2+ alone were refined at 2.6- and 2.25-A resolution, respectively. They serve as standards for comparison with other Mn2+- and Zn2+-containing structures. In these cases, Mn2+ and Zn2+ bind at metal ion site B in a nearly identical position to Mg2+ (Brautigam and Steitz (1998) J. Mol. Biol. 277, 363-377). Two structures of KF bound to a deoxyoligonucleotide that contained a 3'-bridging sulfur at the scissile phosphate were refined at 2.03-A resolution. Although the bridging sulfur compounds bind in a manner very similar to that of the normal oligonucleotides, the presence of the sulfur changes the metal ion binding properties of the active site such that Mn2+ and Zn2+ are observed at metal ion site B, but Mg2+ is not. It therefore appears that the ability of the bridging sulfur compounds to exclude nonthiophilic metal ions from metal ion site B explains the low activity of KF exonuclease on these substrates in the presence of Mg2+ (Curley et al. (1997) J. Am. Chem. Soc. 119, 12691-12692) and that the 3'-bridging atom of the substrate is influencing the binding of metal ion B prior to catalysis.

Binding Sites↗

PubMed1999

Role of a serine/threonine kinase, Mst1, in megakaryocyte differentiation.

Platelets, which play a central role in thrombosis and hemostasis, develop from megakaryocytes. Signal transduction originated from the megakaryocyte growth and development factor, the Mpl ligand, which leads to megakaryocyte differentiation, polyploidization, and maturation, has been gradually characterized. In this study, we report the inducibility of Mst1, a recently described serine/threonine kinase, by Mpl ligand and the effect of its induced expression on megakaryocyte differentiation. The steady-state level of mst1 message and Mst1-associated kinase activity increased in response to Mpl ligand. Ectopic expression of human mst1 in a mouse megakaryocytic cell line resulted in a drastic increase in DNA content per cell. Elevated expression of megakaryocyte differentiation markers, such as acetylcholine esterase, PF4, and GPIIb was also observed in hmst1-expressing cells. Activation of p38 MAPK, a known downstream effector of Mst1, was shown to be required for polyploidization, but not for enhanced expression of differentiation markers. Our study thus designates Mst1 as a Mpl ligand-responsive signaling molecule that promotes induction of lineage-specific cellular programming.

Amino Acid Sequence↗

PubMed1999

Study on relationship between anticardiolipin antibody and cerebrovascular diseases.

Serum anticardiolipin antibody (ACA) was measured in 91 patients with cerebral infarction (CI), 42 patients with cerebral hemorrhage (CH) and 30 healthy controls. The results showed that the ACA in CI and CH patients was significantly higher than in controls and IgG-ACA was the most important isotype. Stroke in ACA positive group tended to be recurrent and of multi-focuses. Positive rate of IgG-ACA reached its peak within the first week after stroke onset. The results suggested that ACA was an independent risk factor in CI and CH and might be valuable in stroke prediction.

Aged↗

PubMed1999

T-cell turnover in vivo and the role of cytokines.

In addition to responding to specific antigen, CD8+ T-cells with a memory (CD44hi) phenotype undergo bystander proliferation when exposed to certain cytokines, notably type I interferons (IFN I), in vivo; such proliferation does not require T-cell receptor ligation. Since IFN I is unable to induce proliferation of purified CD44hi CD8+ cells in vitro, stimulation of these cells in vivo may reflect IFN I-dependent release of other cytokines. Evidence is presented that IFN I induces macrophages to synthesize IL-15 mRNA and that, at the protein level, IL-15 causes selective stimulation of CD44hi CD8+ (but not CD4+) cells, both in vitro and in vivo. This finding raises the possibility that synthesis of IL-15 during infection may induce bystander proliferation of memory-phenotype CD8+ cells.

Animals↗

PubMed1999

Localized sinus inflammation in a rabbit sinusitis model induced by Bacteroides fragilis is accompanied by rigorous immune responses.

We evaluated inflammatory and immune responses against Bacteroides fragilis in a rabbit sinusitis model. Bacteroides was inoculated into the left maxillary sinus, and inflammatory (histology, cell number/cytology, lactose dehydrogenase, and apoptosis) and immune responses in the sinus, airway, and peripheral blood (PB) were determined for up to 4 weeks. In the inflamed sinus, the lactose dehydrogenase level was markedly elevated, with neutrophilic infiltration, severe tissue inflammation, and increased apoptosis. Low-grade tissue inflammation was present in the contralateral and sham-operated sinuses, but other parameters remained unchanged, and so did those in the airway and PB in the inoculated rabbits. Serum IgG antibody levels increased rapidly, were highest at 3 weeks, and began to decline at 4 weeks. Cellular immune responses (proliferation and interferon-gamma mRNA expression) against Bacteroides were detected in the PB of all inoculated rabbits. Vigorous immune responses against Bacteroides may have localized but failed to terminate inflammation in the sinus, indicating importance of microenvironmental factors.

Animals↗

PubMed1999

Ectopic expression of the Aspergillus nidulans mitotic inducer, nimA kinase, in megakaryocytes: effect on polyploidization.

Aspergillus nidulans nimA gene encodes a serine/threonine protein kinase (NIMA) whose activity is essential for mitotic entry and chromatin condensation. Both the activity and the abundance of NIMA protein increase at the G2/M transition of the fungal cell cycle. In this study, we report the effects elicited by ectopic expression of nimA on polyploidization in a mouse megakaryocytic line, Y10, which is undergoing an endomitotic cell cycle. A pool of Y10 stable transfectants that have been induced to express nimA displayed a decrease in cell number and an elevated DNA content per cell. NIMA also dramatically enhanced the activity of phorbal 12-myristate 13-acetate toward polyploidization. Analysis of individual nimA transfectants revealed that the DNA content per cell rose in cells expressing high levels of nimA and that the level of cyclin B was reduced as compared to the mock-transfected cells. These effects observed in polyploidizing megakaryocytes are in contrast to those found in A. nidulans and HeLa cells, in which induced nimA expression caused abnormal chromatin condensation and cell cycle arrest. We conclude that high-level expression of nimA in cells programmed to undergo endomitosis could potentiate polyploidization. The challenge now resides in the isolation of the authentic megakaryocyte counterpart of the fungal nimA.

Animals↗

PubMed1999

The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function.

OBJECTIVES: The purpose of this study was to compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function and duration of survival after prolonged ventricular fibrillation (VF). BACKGROUND: We have recently demonstrated that the severity of postresuscitation myocardial dysfunction was closely related to the magnitude of the electrical energy of the delivered defibrillation shock. In the present study, the effects of fixed 150-J low-energy biphasic waveform shocks were compared with conventional monophasic waveform shocks after prolonged VF. METHODS: Twenty anesthetized, mechanically ventilated domestic pigs were investigated. VF was induced with an AC current delivered to the right ventricular endocardium. After either 4 or 7 min of untreated ventricular fibrillation (VF), the animals were randomized for attempted defibrillation with up to three 150-J biphasic waveform shocks or conventional sequence of 200-, 300- or 360-J monophasic waveform shocks. If VF was not reversed, a 1-min interval of precordial compression preceded a second sequence of up to three shocks. The protocol was repeated until spontaneous circulation was restored or for a total of 15 min. RESULTS: Monophasic waveform defibrillation after 4 or 7 min of untreated VF resuscitated eight of 10 pigs. All 10 pigs treated with biphasic waveform defibrillation were successfully resuscitated. Transesophageal echo-Doppler, arterial pressure and heart rate measurements demonstrated significantly less impairment of cardiovascular function after biphasic defibrillation. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher energy monophasic waveform shocks for restoration of spontaneous circulation after 4 and 7 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation.

Analysis of Variance↗

PubMed1999

Immobilization and characterization of beta-galactosidase from the plant gram chicken bean (Cicer arietinum). Evolution of its enzymatic actions in the hydrolysis of lactose.

beta-Galactosidase (beta-D-galactosidase galactohydrolase, EC 3.2.1. 23) isolated and purified from gram chicken bean was immobilized on cross-linked polyacrylamide gel. The activity yield was high and attained up to 72%. Compared with the free enzyme, the immobilized enzyme had a wider operational pH range and better thermal stability. Lyophilized pieces exhibited good stability when stored at room temperature for 60 days and a favorable operational stability when used eight times repeatedly without loss of enzymatic activity under the same conditions. Kinetic data (K(m), V(m), and E(a)) for the free and the immobilized enzymes were determined using O-nitrophenyl-beta-D-galactoside (ONPG) and lactose as substrates. The result of time courses of hydrolysis of lactose showed that beta-galactosidase from the plant gram chicken bean would have a promising application in the hydrolysis of lactose in milk.

Enzyme Stability↗

PubMed1999

A new metal ion interaction in the Tetrahymena ribozyme reaction revealed by double sulfur substitution.

The Tetrahymena ribozyme is a metalloenzyme that catalyzes cleavage of oligonucleotide substrates by phosphoryl transfer. Thiophilic metal ions such as Mn2+, Zn2+ or Cd2+ rescue the >10(3)-fold inhibitory effect of sulfur substitution of the 3'-oxygen leaving group but do not effectively rescue the effect of sulfur substitution of the nonbridging pro-Sp phosphoryl oxygen. We now show that the latter effect can be fully rescued by Zn2+ or Cd2+ using a phosphorodithioate substrate, in which both the 3'-oxygen and the pro-Sp oxygen are simultaneously substituted with sulfur. These results provide the first functional evidence that metallophosphotransferases can mediate catalysis via metal ion coordination to both the leaving group and a nonbridging oxygen of the scissile phosphate.

Animals↗

PubMed1999

Effects of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on human small airway epithelial cells and the protective effects of myo-inositol.

Benzo[a]pyrene (B[a]P), a tobacco-derived carcinogen, induces lung tumors in rodents through its carcinogenic metabolite, anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE). Tumorigenesis is inhibited by dietary myo-inositol in the post-initiation phase. However, little is known about how B[a]PDE and myo-inositol affect normal human lung cells. We addressed this question using untransformed human small airway epithelial (SAE) cells. SAE cell viability decreased <50% in parallel to an increase of apoptotic cells (>20%) 2 days after the cells were treated for 1 h with B[a]PDE (>100 nM). In contrast, the cell number and viability were not altered in A549 human lung cancer cells by B[a]PDE treatment up to 10 microM with <5% apoptotic cells and <10 U/l LDH in the medium. SAE cells retain the features of basal cells in serum-free, low Ca2+ (4 nM) medium up to 4-5 passages, but in serum-supplemented or serum-free, high Ca2+ (1 mM) cultures, they differentiate into non-ciliated epithelial cells expressing Clara cell secretory protein (CCSP). A non-toxic, physiologically relevant dose of B[a]PDE (1 nM) partially inhibited serum and Ca2+-induced SAE cell differentiation. This effect was abolished by wortmannin, a phosphatidylinositol-3 kinase (PI-3K) inhibitor, and PD98059, a mitogen activated protein kinase (MAPK) kinase-1 (MEK1) inhibitor, but not by SB202190, a p38 MAPK inhibitor, or melittin, a protein kinase C inhibitor. Myo-inositol (10-100 microM) did not alter growth or differentiation of untreated SAE or A549 cells, but reversed the inhibitory effect of B[a]PDE on serum and Ca2+-induced SAE cell differentiation when supplemented to the culture after B[a]PDE treatment. This myo-inositol action was not altered by PD98059, wortmannin or melittin, but was partially suppressed by SB202190. Collectively, these results indicate that B[a]PDE inhibits serum-induced SAE cell differentiation, possibly involving activating signals through a PI-3K/MEK1 mediated MAPK pathway, whereas myo-inositol protects SAE cells against this inhibitory effect of B[a]PDE perhaps through both PI-3K/MEK1 and p38 MAPK pathways.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1999

Electrocardiographic prediction of the success of cardiac resuscitation.

OBJECTIVES: To identify a method for predicting the success or failure of a defibrillatory shock such as to avoid potentially detrimental interruptions of cardiopulmonary resuscitation (CPR). Such a method would also guide more optimal programming of automated external defibrillators. DESIGN: Prospective, observational animal study. SETTING: Medical research laboratory in a university-affiliated research and educational foundation. SUBJECTS: Domestic pigs. INTERVENTIONS: Ventricular fibrillation (VF) was electrically induced in 66 domestic pigs. After an interval of between 3 and 5 mins of untreated VF, precordial compression was begun. Electrocardiographic lead 2 was monitored and artifacts produced during precordial compression were removed by digital filtering. MEASUREMENTS AND MAIN RESULTS: In the derivation study, electrical defibrillation restored spontaneous circulation in 30 of the 66 animals. Successfully resuscitated animals had significantly greater coronary perfusion pressure, maximum VF amplitude, mean VF amplitude, and dominant VF frequency. No animals were resuscitated if the coronary perfusion pressure was <8 mm Hg, maximum amplitude was <0.48 mV, mean amplitude was <0.25 mV, or dominant frequency <9.9 Hz independently of the duration of untreated VF. When mean amplitude and dominant frequency were combined, the predictability was further improved. In an additional validation study of 14 animals, consecutive defibrillations were uniformly unsuccessful if the combination of mean amplitude and dominant frequency did not exceed the threshold values obtained in derivation study. CONCLUSION: Mean VF amplitude alone or in combination with dominant frequency of VF was expressed as a numerical score. It served as an objective noninvasive measurement on a par with that of coronary perfusion pressure for predicting the success of defibrillation. As such, it minimizes the detriment of repetitively interrupting mechanical interventions during CPR for electrical defibrillation when an electrical shock predictably fails to restore an effective rhythm.

Animals↗

PubMed1999

Middle ear pathologic changes associated with chronic anaerobic sinusitis in rabbits.

OBJECTIVE/HYPOTHESIS: To study the histopathologic changes in association with the inflammatory/immune response present in the middle ears of a rabbit model of unilateral chronic anaerobic sinusitis. STUDY DESIGN: New Zealand white rabbits, two at each experimental time point. Normal rabbits and sham-operated animals served as controls. METHODS: Left maxillary sinusitis was induced by inoculating Bacteroides fragilis surgically after closure of the ostium. Cultures, lavages, and mucosa were harvested from bilateral middle ear and sinus cavities at 1, 2, 3, and 4 weeks following inoculation. Parameters analyzed include tissue for histopathologic study, immunoglobulin G antibody (IgG Ab) against B fragilis, and lactate dehydrogenase (LDH) levels in lavage samples, interferon gamma (IFN gamma) messenger RNA (mRNA) expression in mucosal tissue, and bacterial culture. RESULTS: Despite closure of the ostium of the left sinus, mild to moderate dissemination of B fragilis into the right sinus and left and right ears were observed in some but not all rabbits (2/8, 5/7, and 2/8, respectively). Histopathologic changes in the right sinus and middle ears were much less severe in contrast to the severe inflammatory changes in the left sinus. An immune response against B fragilis appeared to occur in the sinuses and ears bilaterally independent of bacterial dissemination, as evidenced by a rise of IgG Ab in lavage fluid and detection of IFNg mRNA. Neither control nor sham-operated animals had detectable levels of IFNg mRNA or IgG Ab. In B fragilis-inoculated rabbits, the magnitude of IgG Ab responses was equivalent in the right and left ear, independent of B fragilis dissemination; IgG Ab levels in the middle ear positively correlated to each other (P < .01) and to the levels in the sinuses (P < .01 and P < .01). LDH levels were closely associated with bacterial growth and degree of tissue inflammation. CONCLUSION: This reproducible model of chronic sinusitis provides an opportunity to study the middle ear infection and inflammatory/immune responses occurring with sinusitis. Our results indicate bilateral middle ear mucosal immune responses to an elicited sinus infection, independent of B fragilis dissemination.

Animals↗

PubMed1999

Extensive conservation of sex chromosome organization between cat and human revealed by parallel radiation hybrid mapping.

A radiation hybrid (RH)-derived physical map of 25 markers on the feline X chromosome (including 19 Type I coding loci and 6 Type II microsatellite markers) was compared to homologous marker order on the human and mouse X chromosome maps. Complete conservation of synteny and marker order was observed between feline and human X chromosomes, whereas the same markers identified a minimum of seven rearranged syntenic segments between mouse and cat/human X chromosome marker order. Within the blocks, the feline, human, and mouse marker order was strongly conserved. Similarly, Y chromosome locus order was remarkably conserved between cat and human Y chromosomes, with only one marker (SMCY) position rearranged between the species. Tight linkage and a conserved gene order for a segment encoding three genes, DFFRY-DBY-UTY in human, mouse, and cat Y chromosomes, coupled with demonstrated deletion effects of these genes on reproductive impairment in both human and mouse, implicates the region as critical for Y-mediated sperm production.

Animals↗

PubMed1999

Stimulation of naïve and memory T cells by cytokines.

On the basis of cell surface markers, mature T cells are considered to have either a naïve or a memory phenotype. These cells exhibit distinct types of kinetic behaviour in vivo. While naïve-phenotype cells persist long term in a non-dividing state, memory-phenotype T cells include cycling cells and exhibit a more rapid rate of turnover; this has also been shown to be true for cells that can be definitively identified as naïve or memory T cells respectively. The number of memory-phenotype (CD44hi) CD8+ T cells entering cell cycle is greatly increased after in vivo exposure to viruses, bacteria or components of bacteria. Accelerated turnover of memory T cells also occurs after the injection of a variety cytokines that are induced by infectious agents, including type I interferon (IFN-I). Although naïve-phenotype T cells do not divide in response to these cytokines, they do exhibit signs of activation, including upregulation of CD69 after exposure to IFN-I. These findings suggest that the dissimilar in vivo kinetics of naïve- and memory-phenotype T cells might reflect their divergent responses to cytokines. Furthermore, the ability of infection-induced cytokines to stimulate non-specific proliferation of memory-phenotype T cells and partial activation of naïve-phenotype T cells implies that they play a complex role during primary immune responses to infectious agents.

Adjuvants, Immunologic↗

PubMed1999

Juzen-taiho-to, a Japanese herbal medicine, modulates type 1 and type 2 T cell responses in old BALB/c mice.

Aging is associated with skewed type 2 (T2) T cell responses that may be modulated by herbal medicines. A group of Japanese herbal medicines, so-called "Hozai," have been used to improve the physical condition of the elderly. One representative "Hozai," Juzen-Taiho-To (JTX) appears to have beneficial effects on cancer patients. In this study we hypothesized that JTX modulated skewed T2 responses in the elderly. T1 and T2 responses against ovalbumin (OVA) were examined in old BALB/c mice fed JTX (0.2% w/w). We measured anti-OVA IgG1, IgG2a, and IgG2b antibody (Ab) levels after the primary and secondary OVA challenges; T1 and T2 responses augment IgG2a/IgG2b Ab and IgG1/IgE Ab production, respectively. We also assessed production of T1 and T2 cytokines (IFN-gamma and IL-5, respectively), and co-stimulatory molecule expression by regional draining lymph node cells. JTX-fed mice had higher IgG2b Ab and IFN-gamma production than controls along with lower IgG1 Ab. JTX did not alter IL-5 production or co-stimulatory molecule expression. Hoelen, an herbal component, induced similar changes. Our results indicate that JTX and Hoelen modulate T cell responses against OVA toward more balanced T1/T2 responses in old BALB/c mice. Such effects of JTX may help prevent the development of diseases associated with immunodisregulation in the elderly.

Aging↗