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Biomedical subjects

E Yamada

Publications and source records attributed to E Yamada.

At least 37 records · Page 2Linked to original sources

Chronic fatigue syndrome in childhood.

Chronic fatigue occurring in previously healthy children and adolescents is one of the most vexing problems encountered by pediatric practitioners. We report three cases, 11, 12 and 13-year-old children, with chronic fatigue syndrome (CFS). They initially developed a low grade fever and generalized fatigue, followed by sleep disturbance and psychosomatic symptoms, and their performance ability deteriorated. They were diagnosed as having CFS on the basis of criteria. To investigate the brain function in CFS patients, we examined the regional cerebral blood flow by single-photon emission-computed tomography (SPECT) with 111 MBq [123I]-iodoamphetamine (123I-IMP) or xenon-computed tomography (Xe-CT), and brain metabolic levels by MR spectroscopy (MRS). Blood flow, expressed as the corticocerebellar ratio (CCR), in the left temporal and occipital lobes was markedly lower in cases 2 and 3 than that in healthy subjects reported by another investigator. In case 1, however, blood flow in the left basal ganglia and thalamus was markedly higher than in healthy subjects. The MR spectroscopy (MRS) study revealed remarkable elevation of the choline/creatine ratio in the patients with CFS. None of our patients exhibited evidence of focal structural abnormalities on MRI. These findings suggest that the various clinical symptoms in CFS patients may be closely related to an abnormal brain function.

Adolescent↗

Cholesterol sulfate, an activator of protein kinase C mediating squamous cell differentiation: a review.

Activity of protein kinase C (PKC) depends on the interaction with polar head-groups of two membrane lipids, i.e., phosphatidylserine and diacylglycerol. We demonstrated that cholesterol metabolism is directly involved in activation of the eta isoform of protein kinase C (PKCeta), which is predominantly expressed in epithelial tissues in close association with epithelial differentiation. We found that PKCeta was activated by cholesterol sulfate (CS), a metabolite of cholesterol formed during squamous cell differentiation. In the presence of CS, phorbol ester only weakly enhanced the activity of PKCeta. CS also activated PKCeta, PKCdelta and PKCepsilon in a dose-dependent manner, when assayed using purified recombinant materials. However, when partially purified materials were used from overexpressing normal human keratinocytes, only PKCeta was activated by CS among the isoforms examined. All the existing lines of evidence, mainly supplied from our laboratory, suggest that CS is involved in a signal transduction of squamous cell differentiation and thereby modifying squamous cell carcinogenesis.

Cell Differentiation↗

Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population.

HLA class I and class II allelic genotypes were determined in 371 unrelated individuals and 309 members of 81 families inhabiting the central Japan area. A total of 20 HLA-A alleles, 16 HLA-Cw alleles, 38 HLA-B alleles, 27 HLA-DRB1 alleles, 15 HLA-DQB1 alleles and 12 HLA-DPB1 alleles were detected. By the two-, three-, four-, five- and six-locus allelic association analyses extracted from the HLA-A to -DPB1 locus, 26 HLA-Cw-B haplotypes, 25 HLA-DRB1-DQB1 haplotypes, 42 HLA-Cw-B-DRB1 haplotypes, 37 HLA-Cw-B-DRB1-DQB1 haplotypes, 29 HLA-A-Cw-B-DRB1-DQB1 haplotypes and 21 HLA-A-Cw-B-DRB1-DQB1-DPB1 haplotypes with the frequencies of higher than 0.005 were recognized. Among 19 HLA-B alleles with the high allele frequencies (above 0.007), 9 HLA-B alleles, B*0702, B*1301, B*3701, B*3901, B*4006, B*4403, B*5201, B*5901 and B*6701 were found to be tightly associated with single HLA-Cw alleles. Most of HLA-DRB1 alleles showed strong associations with single HLA-DQB1 alleles, but DRB1*0802 and DRB1*1401 were associated with two different DQB1 alleles. Extended haplotypes carrying infrequent class I alleles with the allele frequencies of lower than 0.007 were defined by family studies. Gene frequencies and haplotypic associations within the entire HLA classical loci elucidated at the high resolution (four-digital) allelic level will provide useful information on anthropology, marrow donor registry, legal medicine and disease-association studies.

Family↗

Pulmonary veno-occlusive disease in pulmonary Langerhans' cell granulomatosis.

This report describes unusual clinical and pathological findings in a 29-yr-old female with pulmonary Langerhans' cell granulomatosis (LCG). During a 7-yr clinical course her condition deteriorated despite corticosteroid therapy, and she died of respiratory failure and pulmonary hypertension. At autopsy, there were widespread pulmonary veno-occlusive disease (PVOD) lesions as well as abundant advanced and healed lesions of pulmonary LCG composed of multiple cysts and stellate fibrosis. The present case demonstrates that pulmonary Langerhans' cell granulomatosis should be considered as a possible cause of pulmonary veno-occlusive disease.

Adult↗

Ste20-like kinase (SLK), a regulatory kinase for polo-like kinase (Plk) during the G2/M transition in somatic cells.

BACKGROUND: Activation of the cyclin-dependent kinase cdc2-cyclin B1 at the G2/M transition of the cell cycle requires dephosphorylation of threonine-14 and tyrosine-15 in cdc2, which in higher eukaryotes is brought about by the Cdc25C phosphatase. In Xenopus, there is evidence that a kinase cascade comprised of xPlkk1 and Plx1, the Xenopus polo-like kinase 1, plays a key role in the activation of Cdc25C during oocyte maturation. In the mammalian somatic cell cycle, a polo-like kinase homologue (Plk1) also functions during mitosis, but a kinase upstream of Plk is still unknown. RESULTS: We show here that human Ste20-like kinase (SLK), which is a ubiquitously expressed mammalian protein related to xPlkk1, can phosphorylate and activate murine Plk1. During progression through the G2 phase of the mammalian cell cycle, the activity of endogenous SLK is increased. The amount of SLK protein is decreased in quiescent and differentiating cells. Treatment with okadaic acid induces a phosphorylation-dependent enhancement of SLK activity. CONCLUSIONS: We propose that SLK has a role in the regulation of Plk1 activity in actively dividing cells during the somatic cell cycle. SLK itself is suggested to be regulated by phosphorylation.

3T3 Cells↗

The second eye of Japanese patients with unilateral exudative age related macular degeneration.

AIM: To clarify the incidence of choroidal neovascularisation (CNV) and predisposing findings for development of CNV in the second eye of Japanese patients with unilateral exudative age related macular degeneration (AMD). METHODS: The second eyes of unilaterally affected patients with exudative (neovascular) AMD treated in our clinic during the past 10 years (1988-97) were carefully followed up for more than a year. Evidence of CNV was confirmed by fluorescein and indocyanine green angiography. Macular lesions in patients, in whom CNV developed in the second eye, were retrospectively evaluated from patient records. RESULTS: 170 patients met the criteria. The average follow up period was 47 months (range 12-108 months). All patients were Japanese. CNV developed in the second eye in 12 (7%) of 170 patients, 30.3 months on average after the first examination. Cumulative incidence of developing CNV in the second eye using Kaplan-Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3% by 5 years, and was relatively low compared with that in white patients. CNV developed most frequently from serous pigment epithelial detachment (PED) in the macula (58%). Soft drusen were not prevalent and risk of developing CNV was not very high (18%). CONCLUSION: It was confirmed that there were some differences in the incidence and predisposing findings for CNV developing in AMD among Japanese and other Asian patients compared with those in white people. It is important to recognise these differences between the two populations to understand the pathogenesis and epidemiology of AMD.

Adult↗

In vivo osteogenic capability of cultured allogeneic bone in porous hydroxyapatite: immunosuppressive and osteogenic potential of FK506 in vivo.

Fischer or ACI rat marrow cells were obtained from femoral shafts and were cultured to confluence in Eagle's minimal essential medium (EMEM) supplemented with 15% fetal bovine serum. After trypsinization, the cells were subcultured on porous hydroxyapatite (HA; Interpore 500) blocks in the presence of beta-glycerophosphate and 10 nM dexamethasone (Dex). After 2 weeks of subculture, a mineralized bone matrix with osteogenic cells developed on the HA pore surfaces. ACI or Fischer cultured bone tissue/HA constructs were implanted subcutaneously into the backs of Fischer rats and the immunosuppressant FK506 was given to the rats for 4 weeks. Implants were harvested 4 weeks and 8 weeks after insertion. At 4 weeks, the ACI constructs (allografts) showed high levels of osteogenic parameters (alkaline phosphatase [ALP] activity and osteocalcin content) and bone formation was observed together with active osteoblasts without obvious accumulation of inflammatory cells. At 8 weeks, active osteoblasts and progressive bone formation were still observed, while osteogenic parameters remained high and osteocalcin messenger RNA (mRNA) was detected. Without FK506 administration, the allografts showed neither bone formation nor osteocalcin mRNA and there were only trace levels of the osteogenic parameters. In the case of Fischer constructs (isografts), extensive bone formation was detected and all the osteogenic parameters were higher with FK506 than without FK506 at both 4 weeks and 8 weeks. These results indicate that cultured bone tissue/HA constructs possess a high osteogenic potential, even as allografts, and that FK506 not only has an immunosuppressive action, but also promotes bone formation.

Alkaline Phosphatase↗

Postnatal development of synovial capillaries of rats with special reference to permeability.

The size of a substance is a major factor determining whether it can permeate the wall of synovial capillaries. The maximum diameter of particles that can move across the synovial capillary wall has generally been thought to be 50 nm. We studied the permeability of the synovial capillaries of the rat between day 20 and 30 after birth using a polystyrene particle whose diameter was 240 nm. In addition using lecithin-coated polystyrene particles, we studied the maturation of the barrier function supported by endothelial and peripheral cells against foreign bodies. Lecithin-coated particles were found within the fibroblast-like synovial cells near the capillary in the 20 day-old rats, while non-coated particles remained in the endothelial wall and in the peripheral cells of capillaries. In the 30 day-old rats, lecithin-coated particles were present in the peripheral cells and the neighboring synovial cells; however, the non-coated particles were never found in the synovial or perisynovial cells. The present study shows that the size of the transportable substance by transcytosis may be larger than previously thought. Furthermore, the synovial capillaries functionally changed between day 20 and 30 suggesting that active movement of the joint led to the functional maturation of the synovial capillaries.

Animals↗

Zebrafish genetic map with 2000 microsatellite markers.

The zebrafish is the first vertebrate organism used for large-scale genetic screens seeking genes critical to development. These screens have been quite successful, with more than 1800 recessive mutations discovered that speak to morphogenesis of the vertebrate embryo. The cloning of the mutant genes depends on a dense genetic map. The 2000 markers we present here, using microsatellite (CA) repeats, provides 1.2-cM average resolution. One centimorgan in zebrafish is about 0. 74 megabase, so, for many mutations, these markers are close enough to begin positional cloning by YAC walks.

Animals↗

Hyperoxia causes decreased expression of vascular endothelial growth factor and endothelial cell apoptosis in adult retina.

Mice or humans with photoreceptor degenerations experience permeability and dropout of retinal capillaries. Loss of photoreceptors results in decreased oxygen usage and thinning of the retina with increased oxygen delivery to the inner retina. To investigate the possibility that increased tissue oxygen plays a role in the vascular damage, we exposed adult mice to hyperoxia, which also increases oxygen in the retina. After 1, 2, or 3 weeks of hyperoxia, there was a statistically significant decrease in retinal vascular density that was not reversible, and endothelial cell apoptosis was demonstrated by TUNEL staining. Mice exposed to hyperoxia and mice with photoreceptor degeneration both showed decreased expression of VEGF in the retina. After complete or near-complete degeneration of photoreceptors, there was increased expression of VEGF in RPE cells, which may explain the association of photoreceptor degeneration and neovascularization in or around the RPE. Increased expression of VEGF in photoreceptors of transgenic mice failed to prevent hyperoxia-induced retinal capillary dropout. These data suggest that increased oxygen in the retina, either by increased inspired oxygen or by photoreceptor degeneration, results in endothelial cell death and dropout of capillaries. Decreased expression of VEGF may be a contributing factor, but the situation may be more complicated for mature retinal vessels than it is for immature vessels, because VEGF replacement does not rescue mature retinal vessels, suggesting that other factors may also be involved.

Animals↗

Neurochemical characteristics and behavioral responses to psychological stress in ovariectomized rats.

The present study was designed to clarify the time-dependent changes in brain monoamine turnover in the frontal cortex, hypothalamus, hippocampus, septum and amygdala after ovariectomy, and the difference in behavioral responses to psychological stress between sham-operated and ovariectomized (OVX) rats. At 2 and 4 weeks after ovariectomy, the turnover rates of dopamine and norepinephrine in all of the brain regions examined did not differ significantly between the sham-operated and OVX rats. However, 5-hydroxytryptamine (5-HT) turnover in all of the brain regions at 2 weeks after OVX was significantly lower than that in sham-operated rats. This difference was greater in the hypothalamus than in other brain regions. At 4 weeks after ovariectomy, 5-HT turnover in all of the brain regions examined was not significantly different between sham-operated and OVX rats. At 2 and 4 weeks after ovariectomy, exploratory behaviour (e.g., locomotor activity, head- dipping, crossing and rearing behaviours) in a non-stressed ovariectomy group did not differ from that in a non-stressed sham-operation group. Locomotor activity and the number of head-dips and crossings significantly (P<0.05) increased after repeated exposure to psychological stress for 5 days in sham-operated rats, but not in those at 2 weeks after OVX. At 4 weeks after ovariectomy, locomotor activity and the number of crossings and rearings in sham-operated and OVX rats were not significantly different in the psychological stress and non-stress groups. However, the number of head-dips significantly (P<0.05) increased with psychological stress in the sham-operated rats, but not in OVX rats. These results suggest that female gonadal hormones may play an important role in the regulation of brain 5-HTergic systems. These interactions between gonadal hormones and 5-HT metabolism may be related to 5-HT-related neuropsychiatric disorders.

Amygdala↗

Influence of dobutamine or exercise stress on the results of pulsed-wave Doppler assessment of myocardial velocity.

BACKGROUND: Pulsed-wave Doppler assessment of myocardial velocity (MDV) may permit a more quantitative interpretation of stress echocardiography. This technique has been used with dobutamine echo (DbE), but exercise echo (ExE) may be preferred in patients who are able to exercise maximally. The influence of these stressors on the results of MDV are undefined. PURPOSE: This study sought to determine whether differences between the physiology of DbE and ExE could influence the MDV responses to stress and whether interpretative criteria should be different with exercise or dobutamine stress. METHODS: DbE or ExE was performed in 105 patients tested for known or suspected coronary artery disease. Pulsed-wave MDV was obtained in basal segments of anteroseptal, septal, anterior, posterior, lateral, and inferior walls in the apical views at rest and at peak doses of dobutamine or immediately after exercise. Segments were classified as normal or abnormal (ischemia or scar) according to results of 2-dimensional echocardiography, and MDV obtained at rest and stress was compared by using analysis of variance. RESULTS: Resting heart rate was similar before both dobutamine and exercise, but heart rate at peak dobutamine exceeded that after exercise (137 +/- 10 vs 115 +/- 22, P <.01). For both ExE and DbE, MDV was significantly greater at rest and stress in normal than in abnormal segments. Stress MDV in both normal and abnormal segments was greater with DbE than with ExE (17.0 +/- 4.8 cm/s vs 10. 3 +/- 3.4 cm/s, P <.001 for normal segments and 10.7 +/- 4.4 cm/s vs 7.9 +/- 3.3 cm/s, P <.001 for abnormal segments. Increase in MDV/Deltaheart rate induced by DbE was greater than by ExE in normal (0.14 +/- 0.07 cm/s. beat for DbE and 0.09 +/- 0.08 cm/s. beat for ExE; P <.05) but similar in abnormal segments (0.06 +/- 0.07 cm/s. beat for DbE and 0.05 +/- 0.09 cm/s. beat for ExE). MDV correlated better with peak heart rate at ExE (r = 0.56, P <.01) than at DbE (r = 0.28, P <.01). CONCLUSIONS: MDV responses to exercise and pharmacologic stress appear to be different, reflecting differences in inotropy, loading, and the timing of imaging. These findings may influence the ability of MDV to differentiate normal from abnormal stress echocardiography responses.

Aged↗

Dramatic inhibition of retinal and choroidal neovascularization by oral administration of a kinase inhibitor.

The most common cause of new blindness in young patients is retinal neovascularization, and in the elderly is choroidal neovascularization. Therefore, there has been a great deal of attention focused on the development of new treatments for these disease processes. Previous studies have demonstrated partial inhibition of retinal neovascularization in animal models using antagonists of vascular endothelial growth factor or other signaling molecules implicated in the angiogenesis cascade. These studies have indicated potential for drug treatment, but have left many questions unanswered. Is it possible to completely inhibit retinal neovascularization using drug treatment with a mode of administration that is feasible to use in patients? Do agents that inhibit retinal neovascularization have any effect on choroidal neovascularization? In this study, we demonstrate complete inhibition of retinal neovascularization in mice with oxygen-induced ischemic retinopathy by oral administration of a partially selective kinase inhibitor that blocks several members of the protein kinase C family, along with vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases. The drug also blocks normal vascularization of the retina during development but has no identifiable adverse effects on mature retinal vessels. In addition, the kinase inhibitor causes dramatic inhibition of choroidal neovascularization in a laser-induced murine model. These data provide proof of concept that pharmacological treatment is a viable approach for therapy of both retinal and choroidal neovascularization.

Administration, Oral↗

Immunostimulatory oligodeoxynucleotide induces TH1 immune response and inhibition of IgE antibody production to cedar pollen allergens in mice.

BACKGROUND: Immunotherapy for cedar pollinosis makes use of multiple injections of allergens, but its effectiveness remains controversial. Recent studies indicate that immunization with certain protein antigens and immunostimulatory DNA sequence (ISS) oligodeoxynucleotides (ODNs) represent a potential approach to allergen-specific immunotherapy. OBJECTIVE: We determined whether the coadministration of 2 major protein allergens, Cry j 1 and Cry j 2, of Japanese cedar pollen and ISS-ODN (5'-TGACTCTGAACGTTCGAGATGA-3') improves the immune responses induced by protein allergens in BALB/c mice. METHODS: Mice were primed intradermally with allergens or ISS-ODN in saline solution and boosted with allergens in alum, and other mice were primed with allergens in alum and boosted with allergens/ISS-ODN. Allergen-specific IgG2a and IgG1 antibody responses were measured by means of ELISA in sera after ODN injection, and allergen-specific IgE antibody production was measured by the passive cutaneous anaphylaxis reaction. IFN-gamma and IL-4 releases were also measured by ELISA in the supernatants of allergen-stimulated spleen cells. RESULTS: The coadministration of allergens/ISS-ODN increased IgG2a titers and IFN-gamma release in both groups of mice, whereas it decreased IgG1 titers and IL-4 release in comparison with control mice injected with allergens/mutant ODN. The coadministration additionally inhibited IgE antibody production. CONCLUSION: The data demonstrate that the coadministration of cedar pollen allergens and ISS-ODNs before secondary T(H2) and IgE responses or during ongoing primary T(H2) and IgE responses brings about a T(H1)-shifted immune response and inhibition of IgE antibody production, suggesting that this coadministration strategy may provide a novel type of immunotherapy for cedar pollinosis.

Adjuvants, Immunologic↗

Tocoretinate inhibited the contraction of collagen gel matrices by human dermal fibroblasts with tenascin-C expression.

Retinoids are strong tissue modifiers and have been used to treat severe acne, keloids and photo-aged skin. Tocoretinate (TR), ester bound retinoic acid and tocopherol, has been topically applied for skin ulcers and, more recently, for sclerotic skin diseases. To clarify the mechanism of tissue softening by retinoids and TR, we investigated their effects on the contraction of hydrated type-1 collagen gel matrices by human dermal fibroblasts and on tenascin-C expression. TR, 13-cis-retinoic acid/isotretinoin and all trans-retinoic acid significantly inhibited collagen gel matrices contraction at concentrations from 10(-4) to 10(-8) M without significant changes of the fibroblast growth. TR and the other two retinoids dose-dependently induced tenascin-C expression in the fibroblasts. Since tenascin-C is involved in cellular detachment and tissue remodeling, these results suggest that TR and other retinoids down-regulated the tensile tension of fibroblasts in collagen gel matrices by the induction of tenascin-C.

Cells, Cultured↗

Frontal brain electrical activity in infants of depressed and nondepressed mothers: relation to variations in infant behavior.

In previous studies, infants of depressed mothers have been found to exhibit reduced left frontal brain electrical activity (EEG). The left frontal region has been hypothesized to mediate social approach behaviors and positive affective expression. These findings raise important questions about the cause and nature of atypical EEG patterns in infants of depressed mothers. The present study begins to address some of these questions by examining whether or not variations in patterns of frontal brain activity in infants of depressed and nondepressed mothers are related to variations in infant behavior as observed in naturalistic situations. If such relations exist, are they specific to certain behaviors hypothesized to be mediated by the frontal region (i.e., positive approach behaviors)? Frontal and parietal brain electrical activity was recorded from 14- to 15-month old infants of depressed versus nondepressed mothers during a baseline condition and during conditions designed to elicit interest and positive affect. Infant behavior was observed in naturalistic play conditions, with and without mother, on a separate day from EEG testing. Mothers provided information on infant temperament. Infants of depressed mothers showed less affection and touching of their mothers. For infants of depressed mothers only, reduced left frontal brain activity was found to be related to lower levels of affection toward mother, but not to infant temperament. Furthermore, increased generalized frontal activation was found to be related to higher levels of negative affect, hostility, and tantrums and aggression. Relations between infant brain activity and behavior were not found for parietal EEG activity. These results suggest that infant frontal electrical brain activity is related to variations in infant behavior, especially those involved in positive affiliative behavior and the expression and regulation of negative affect. The nature and cause of atypical patterns of brain activity and question of whether such atypical patterns of frontal brain activity predispose infants to affective disorders in later life are discussed.

Depression↗

Immunoglobulins of untreated Graves' patients with or without thyrotropin receptor antibody (determined by porcine thyrocytes) universally elicit potent thyroid hormone-releasing activity in cultured human thyroid follicles.

Thyrotropin receptor antibody (TRAb), comprising thyrotropin binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb), both of which are conventionally determined using porcine thyrocytes in Japan, is not always positive in patients with untreated Graves' disease. To elucidate whether immunoglobulin G (IgG) obtained from TBII/TSAb-positive (+) or negative (-) Graves' disease patients are responsible for hyperthyroidism, we investigated the thyroid hormone-releasing activity (THRA) of these IgGs in human thyroid follicles in suspension culture, in which bovine thyrotropin (bTSH) is detectable even at 0.1 microU/mL. Human thyroid follicles, obtained from Graves' disease patients by subtotal thyroidectomy, were cultured in serum-free F-12/RPMI-1640 medium supplemented with bTSH or purified Graves' IgGs. After preculturing for 3 days, 125I was added, and after an additional 3 days of culture, 1251 incorporated into the thyroid follicles and organic 125I released into the culture medium (mainly 1251 -T4 + 125I-T3) were counted. Seventy TBII(+)/TSAb( + )-, 3 TBII( + )/TSAb( - )-, and 3 TBII( - )/TSAb( + )- patients with untreated Graves' disease were all positive for THRA, which became undetectable in spontaneous remission obtained after several years of medical treatment. The THRA was equivalent to 0.8-230 microU/mL bTSH. Furthermore, 2 TBII(-)/TSAb(-) patients were significantly positive for THRA. This TBII(-)/TSAb(-)IgG stimulated human thyrocytes to produce cyclic adenosine monophosphate (cAMP), and this was partially inhibited by antihuman IgG antibody. The THRA induced by TBII(+)/TSAb(+) IgGs as well as TBII(-)/TSAb(-) IgG was inhibited by blocking-type TRAb obtained from TBII(+) patients with myxedema. There was a significant correlation between THRA and TSAb. These in vitro findings suggest that all IgGs obtained from untreated Graves' patients (n = 78) elicit potent THRA in human thyroid follicles in suspension culture. Because the TBII(-)/TSAb(-) IgGs can stimulate cAMP production in human but not in porcine thyrocytes, they probably recognize epitope(s) of TSH-binding sites specific to the human thyrotropin (hTSH) receptor. Furthermore, we have demonstrated that the thyroid gland of hyperthyroid Graves' patients is stimulated by IgG(s) equivalent to at least 0.8 microU/mL bTSH (about 5 microU/mL hTSH) in vitro.

Animals↗

The effect of da-fang-feng-tang on treatment of type II collagen-induced arthritis in DBA/1 mice.

Da-Fang-Feng-Tang (DFFT), which is believed to be effective for treating human rheumatoid arthritis (RA), was given to DBA/1 mice at the onset of type II collagen-induced arthritis (CIA) to examine its effect. Granules of the crude DFFT extract were administered by gastric gavage at a dose of 1.6 g/kg/day for 12 weeks, starting the day CIA began. The levels of anticollagen IgG antibody were significantly decreased in the sera of the DFFT-treated group compared with the control group from weeks 2 to 7 after the onset of CIA. The severity of arthritis in the DFFT-treated group was markedly alleviated when compared with the control group. In addition, histological examination of the DFFT-treated group showed less cartilage and bone erosion. These results suggest that administration of DFFT suppressed the development of CIA in mice and support the belief that DFFT is effective in treating human RA.

Animals↗