Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 163 records · Page 9Linked to original sources

PubMed2000

Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography.

Recent advances in imaging modalities enable the identification of small hepatocellular nodules. Among the imaging techniques currently used for detecting hepatocellular carcinomas (HCC), computed tomography (CT) during arterial portography (CTAP) is one of the most sensitive techniques available for detecting hemodynamic change. Even so, well-differentiated HCCs that display only limited hemodynamic change, a feature shared with nonmalignant hepatocellular nodules, are not always detectable by CTAP. To improve our ability to distinguish well-differentiated HCCs from nonmalignant hepatocellular nodules, we have attempted to clarify how the characteristics of the nodules are shown by each imaging technique. We studied the imaging and pathological characteristics of 31 nodules (in 22 patients) detected by ultrasonography (US), but not by CTAP. Histological diagnoses were as follows: HCC, 17 of 31 nodules (55%); high-grade dysplastic nodules, 1 of 31 (3%); and nonmalignant nodules, 13 of 31 (42%). Neither digital substraction angiography (DSA) nor CT arteriography (CTA) were able to detect any of the nodules. Detection rates for plain CT were: 5 of 17 (29%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 1 of 13 (8%) nonmalignant nodules. Detection rates for T1/T2-weighted magnetic resonance imaging (MRI) were: 4 of 17 (24%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 3 of 13 (23%) nonmalignant nodules. Dynamic CT and dynamic MRI provided no additional information. In conclusion, there is some probability that hepatocellular nodules detected by US, but not by CTAP, are HCC. Presently, it is difficult to distinguish between benign nodules and malignant ones with these imaging techniques, and our findings indicate that biopsy may be advisable for nodules detected under these conditions.

Adult↗

PubMed2000

Does a relationship exist between the urate pool in the body and lipid peroxidation during exercise?

In this study, we investigated whether a relationship exists between the levels of urate in vivo and lipid peroxidation during exercise. Seven healthy male subjects performed exhaustive cycling exercise under the following three conditions. The levels of urate, thiobarbituric acid reactive substances (TBARS) and allantoin in plasma and urine were examined before exercise and during a 3h recovery period. (1) Benzbromarone administration experiment: benzbromarone (an uricosuric agent) was administered orally the day before exercise. (2) IMP administration experiment: inosine 5'-monophosphate disodium salt (a precursor of urate) was administered orally the day before exercise. (3) Control experiment: no test substance was administered. The main results obtained were as follows. Plasma urate levels and total peroxyl radical-trapping antioxidant parameter (TRAP) for deproteinized plasma in the resting period significantly decreased depending on the treatment, in the order of IMP> control > benzbromarone. A significant positive correlation was evident between plasma urate levels and TRAP values for deproteinized plasma. The increase in plasma levels of allantoin was observed only in the case of IMP treatment. A significant negative correlation between plasma levels of urate in the resting period and the amounts of urinary TBARS excreted during the recovery period was recognized. These results suggest that the urate level in vivo before exercise is a factor influencing lipid peroxidation during exhaustive exercise. Furthermore, these findings support the view that urate may serve as an important freeradical scavenger in vivo.

Adult↗

PubMed2000

Is allantoin in serum and urine a useful indicator of exercise-induced oxidative stress in humans?

To assess whether allantoin levels in serum and urine are influenced by exhaustive and moderate exercise and whether allantoin is a useful indicator of exercise-induced oxidative stress in humans, we made subjects perform exhaustive and moderate (100% and 40% VO2max) cycling exercise and examined the levels of allantoin, thiobarbituric acid reactive substances (TBARS) and urate in serum and urine. Immediately after exercise at 100% VO2max, the serum allantoin/urate ratio was significantly elevated compared with the resting levels while the serum urate levels was significantly elevated 30 min after exercise. The serum TBARS levels did not increase significantly compared with the resting levels. Urinary allantoin excretion significantly increased during 60 min of recovery after exercise, however, urinary urate excretion decreased significantly during the same period. The urinary allantoin/urate ratio also rapidly increased during 60 min of recovery after exercise. Urinary TBARS excretion decreased during the first 60 min of the recovery period and thereafter significantly increased during the latter half of the recovery period. On the contrary, after 40% VO2max of exercise, no significant changes in the levels of urate, allantoin and TBARS in serum or urine were observed. These findings suggest that allantoin levels in serum and urine may reflect the extent of oxidative stress in vivo and that the allantoin which appeared following exercise may have originated not from urate formed as a result of exercise but from urate that previously existed in the body. Furthermore, these findings support the view that allantoin in serum and urine is a more sensitive and reliable indicator of in vivo oxidative stress than lipid peroxidation products measured as TBARS.

Adult↗

PubMed2000

Endotoxin and cytokine regulation of toll-like receptor (TLR) 2 and TLR4 gene expression in murine liver and hepatocytes.

Toll-like receptor (TLR) 2 and TLR4 are members of the interleukin-1 receptor (IL-1R) family and transduce similar signals as IL-1R in response to bacteria and bacterial components. In this study, we investigated the regulation of their gene expression in murine tissues, especially in the liver and hepatocytes. When mice were administered lipopolysaccharide (LPS), TLR2 mRNA was upregulated in the brain, heart, lung, liver, and kidney. In contrast, it was downregulated in the spleen. TLR4 mRNA was decreased in the brain. In the heart and lung, it increased, and it was not affected in the liver, kidney, and spleen. TLR mRNA was further analyzed in the liver and hepatocytes. Like LPS treatment, administration of IL-1, IL-6, or tumor necrosis factor (TNF) upregulated TLR2 mRNA. However, none of them affected the TLR4 mRNA level. In primary cultured hepatocytes, TLR2 mRNA was upregulated by LPS, IL-1, or TNF but not by IL-6 or dexamethasone. None of them affected TLR4 mRNA expression. Similar responses were observed in the murine hepatoma cell line Hepa 1-6. These results suggest that in infection with gram-negative bacteria, LPS and proinflammatory cytokines differentially regulate gene expression of TLR2 and TLR4 in murine hepatocytes, which may lead to pathologic and host defense reactions in the liver.

Animals↗

PubMed2000

IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor.

IL-6 and tumor necrosis factor (TNF)-alpha have been proven to play an important role in the development of rheumatoid arthritis (RA). It is well known that TNF-alpha induces IL-6 production from synovial cells as well as their proliferation. The effect of IL-6 on synovial cells, however, is not clear. An in vitrostudy was performed to determine the effect of IL-6 on the proliferation of synovial cells. Fibroblastic synovial cells isolated from the synovial tissues of eight RA patients were employed after the third to sixth passages. IL-6 in the presence of soluble IL-6 receptor (sIL-6R) inhibited the proliferation of synovial cells in a dose-dependent manner in seven cases without increasing the number of necrotic or apoptotic cells, while TNF-alpha increased synovial cell proliferation in all cases. The inhibitory effect of IL-6 was observed only in the presence of sIL-6R although small amounts of IL-6R were detected in these cells by RT-PCR analysis. However, anti-IL-6R or anti-gp130 mAb treatment increased spontaneous growth of synovial cells in all eight cases, suggesting that endogenous IL-6 and a small amount of IL-6R expressed in synovial cells suppressed their growth without exogenous IL-6 or sIL-6R. In addition, the IL-6-sIL-6R complex reduced the TNF-alpha-induced proliferation of synovial cells while TNF-alpha induced their IL-6 production. These data suggest that IL-6 may act as a negative feedback factor for TNF-alpha-induced synovial cell growth.

Arthritis, Rheumatoid↗

PubMed2000

Seroprevalence of antibodies to Chlamydia spp. in human immunodeficiency virus-infected subjects in Japan.

To evaluate the seropositivity of Chlamydia spp. in human immunodeficiency virus (HIV)-infected subjects in Japan, Chlamydia-specific antibodies in sera collected from 106 HIV-infected subjects were measured by the microimmunofluorescence test. The prevalence of C. pneumoniae-specific IgA, C. trachomatis-specific IgG and IgA and mean titers were significantly higher in the homosexual and heterosexual HIV-infected subjects than in the hemophilic patients and HIV-negative controls. These data indicate that the higher C. pneumoniae and C. trachomatis seroprevalence among HIV-infected subjects is probably due to an HIV risk factor, such as promiscuous sexual behavior, rather than to HIV infection itself.

Adolescent↗

PubMed2000

Annexin VII as a novel marker for invasive phenotype of malignant melanoma.

Both F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. While examining the genetic difference between the two sublines, we found a marked reduction of annexin VII expression in BL6 cells. In addition, fusion cell clones of both sublines were as poorly metastatic as F10 cells after subcutaneous injection, and contained the annexin VII message as abundantly as F10 cells. Hence, we examined whether the annexin VII expression was correlated with the less malignant phenotype of clinical cases by immunohistochemistry. Immunoreactivities to anti-annexin VII antibody in melanoma cells were evaluated quantitatively by using skin mast cells as an internal positive control. Eighteen patients with malignant melanoma were divided into two groups: lymph node metastasis-negative and positive groups. The ratio of numbers of patients positive versus negative to the antibody was significantly larger in the former than in the latter group. These results not only indicated that annexin VII serves as a marker for less invasive phenotype of malignant melanoma, but also suggested a possible role of annexin VII in tumor suppression.

Adolescent↗

PubMed2000

Molecular characterization and diagnostic value of Taenia solium low-molecular-weight antigen genes.

Neurocysticercosis (NCC) caused by infection with the larvae of Taenia solium is an important cause of neurological disease worldwide. In order to establish an enzyme-linked immunosorbent assay (ELISA) for this infection using recombinant proteins, we carried out molecular cloning and identified four candidates as diagnostic antigens (designated Ag1, Ag1V1, Ag2, and Ag2V1). Except for Ag2V1, these clones could encode a 7-kDa polypeptide, and Ag2V1 could encode a 10-kDa polypeptide. All of the clones were very similar. Except for Ag2V1, recombinant proteins were successfully expressed using an Escherichia coli expression system. Immunoblot analysis of NCC patient sera detected recombinant proteins, but because reactivity to recombinant Ag1 was too weak, Ag1 was not suitable as an immunodiagnostic antigen. So, Ag1V1 and Ag2 were chosen as ELISA antigens, and the Ag1V1/Ag2 chimeric protein was expressed. Of 49 serum samples from NCC patients confirmed to be seropositive by immunoblot analysis, 44 (89.7%) were positive by ELISA. No assays of serum samples from patients with other parasitic infections recognized the Ag1V1/Ag2 chimeric protein. The Ag1V1/Ag2 chimeric protein obtained in this study had a high value for differential immunodiagnosis.

Amino Acid Sequence↗

PubMed2000

Expression of estrogen receptor alpha and beta mRNAs in prostate cancers treated with leuprorelin acetate.

OBJECTIVE: The discovery of a novel estrogen receptor (ER), ER-beta, has given rise to new possibilities regarding estrogen's roles in the prostate. Although ER-beta is reported to be expressed preferentially in the rat prostate, its expression in the human prostate and relationship to cancer development has not been investigated. Thus the purpose of the study was to examine mRNA levels of ER-alpha and ER-beta in benign prostatic hyperplasia and prostate carcinoma. METHODS: Samples of 15 prostate cancers obtained at radical prostatectomy were examined. All the patients had been maintained on androgen withdrawal therapy for at least 3 months. ER-alpha and ER-beta mRNAs were measured with a competitive PCR technique. RESULTS: Both ER-alpha and ER-beta mRNAs were detected in all of the prostate cancer tissues examined, as well as in PC3 and LNCap cells, although the levels varied among specimens. Interestingly, both types were significantly decreased in cases with lymph node metastasis. However, there was no correlation between ER mRNA levels and any other clinicopathological parameters. CONCLUSIONS: (1) Both ER-alpha and ER-beta mRNAs are expressed in prostate cancer and (2) expression of ER mRNA may not be related to cancer progression but may be negatively correlated with metastasis.

Aged↗

PubMed2000

A role for heterologous gap junctions between melanoma and endothelial cells in metastasis.

F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found that connexin (Cx) 26 is upregulated in BL6 cells. To examine gap junction formation, we devised a coculture system, in which an opened vein segment was placed at the bottom of a culture dish and then dye-labeled melanoma cells were seeded onto it. Immunohistochemistry indicated that the vein segment preserved the integrity of the endothelial monolayer. In this system, BL6 cells could transfer dye into endothelial cells but F10 cells could not. Transfection with wild-type Cx26 rendered F10 cells competent for coupling with endothelial cells and as spontaneously metastatic as BL6 cells. Conversely, transfection with a dominant-negative form of Cx26 rendered BL6 cells deficient in coupling and less metastatic. In human melanoma lesions, the level of Cx26 expression was low in melanoma cells residing in the basal layer, but significantly upregulated in melanoma cells invading the dermis. The results suggested that Cx26 plays a role in intravasation and extravasation of tumor cells through heterologous gap junction formation with endothelial cells.

Animals↗

PubMed2000

In vitro skin penetration and degradation of peptides and their analysis using a kinetic model.

The main purpose of this study was to estimate the net percutaneous absorption of physiologically active peptides in vitro. The degradation of two peptides, Leu-enkephalin (Enk) and Tyr-Pro-Leu-Gly amide (TPLG), during skin penetration and on the dermal side following penetration, and the prevention of degradation by some protease inhibitors, were investigated using rat skin in vitro. In addition, these permeation and degradation data were analyzed using a kinetic model. These peptides were rapidly degraded in the receptor fluid of a Franz diffusion cell (rate constant: 0.977 h(-1) for Enk and 0.250 h(-1) for TPLG). The addition of phenylmethylsulfonyl fluoride (PMSF) and phenanthroline and the pretreatment of skin with these inhibitors prevented almost completely any degradation in the receptor fluid and skin, respectively. The pretreatment of skin with PMSF and phenanthroline had no effect on the penetration of dextran (1000 Da). The degradation rate constant during skin penetration, calculated from the difference in the penetration rate constants via pretreated and untreated skins, was also high (0.037 h(-1) for Enk and 0.050 h(-1) for TPLG). A kinetic model including an input rate (zero-order), the permeation rate across the viable skin (first-order) and the degradation rate in skin (first-order) was sufficient to describe the apparent steady-state flux of the peptides through skin. We have, thus, established a method for measuring the true flux of peptides across skin in vitro and a kinetic model which simply describes the skin penetration of peptides.

Administration, Cutaneous↗

PubMed2000

[Development of patient-friendly preparations(II): Preparation and characterization of carrageenan gel containing polyethylene (oxide)].

The pharmaceutical utility of the allopurinol gel (APNgel) which consists of allopurinol (APN), carrageenan (kappa-CG or iota-CG) and polyethylene (oxide) (Alkox) was investigated as a possible material for an oral dosage preparation for ease in handling and/or swallowing. The gel formation was studied as a function of a variety of the concentration of Alkox and/or CG added. The APNgel gelled with kappa-CG was not appropriate to the oral dosage form because of its original taste and odor. In contrast, since iota-CG has no odor and/or taste, we added iota-CG as a gel material. From the investigation of the gelation behavior and the handling of the gelled material, the preferred composition of APNgel (Alkox: iota-CG% ratio) seemed to be that of 0.5:2.0, 1.0:2.0 and 2.0:2.0. The gel strength and the in vitro assessment of the adhesiveness of APNgels were evaluated using a creep meter. The gel strength of the APNgel was affected by the amount of the added Alkox. From the in vitro assessment of the adhesiveness of APNgels, the adhesiveness of APNgel increased with an increase in the amount of added Alkox. The release behavior of APN from APNgels was investigated by the paddle bead method, mimicking the chewing action in mouth. The APNgel was sheared by the beads and the release of APN completed within 480 s. From the results of the sensory test, APNgel consisting of 2.0% iota-CG and 1.0% Alkox seemed to be favorite to the jelly-like preparation.

Adult↗

PubMed2000

Inverse relationship of expression between GM3 and globo-series ganglioside in human renal cell carcinoma.

Renal cell carcinoma (RCC) is highly metastatic. We previously showed that expression of globo-series ganglioside is associated with the metastatic potential of RCC. However, the mechanism of metastasis remains largely unknown, and there is no effective therapy for metastasis. It was recently shown that induction of differentiation of colon cancer cells by brefeldin A was accompanied by an increase of GM3 with a concomitant decrease of neolacto-series gangliosides. To get a clue to a new method of therapy for RCC, we investigated whether the similar changes occur in RCC cells expressing globo-series ganglioside. Growth suppression and an increase of GM3 simultaneous with a decrease of monosialosyl galactosyl globoside, a member of globo-series gangliosides, were observed in human RCC cell line ACHN following brefeldin A treatment. The resultant change of the ganglioside profile is inversely related to the ganglioside pattern associated with the malignant potential of RCC and almost coincided with that representative of RCC cases showing favorable prognoses. It is suggested that the inverse relationship of expression between GM3 and globo-series ganglioside is reflected on the degree of malignancy of RCC, and may be useful as one of the indicators for exploiting treatment methods of RCC.

Brefeldin A↗

PubMed2000

Association of renal cell carcinoma antigen, disialylgalactosylgloboside, with c-Src and Rho A in clustered domains at the surface membrane.

Disialylgalactosylgloboside (DSGG), defined by monoclonal antibody RM2, is a renal cell carcinoma (RCC)-associated antigen which mediates adhesion of RCC TOS-1 cells to certain lung tissue target cells. This adhesion process may initiate preferential lung metastasis of RCC. Ganglioside GM3 is a B16 melanoma-associated antigen which similarly adheres to target cells and promotes consequent metastasis. In view of the close association of GM3-enriched microdomain with transducer molecules c-Src, Rho A, and FAK in B16 cells, we investigated the organizational status of DSGG in RCC cell line TOS-1, with the following results: i) DSGG, but not monosialylgalactosylgloboside, showed extensive clustering at the TOS-1 cell surface; ii) a low-density membrane fraction isolated from TOS-1 cells contained >95% of cellular DSGG, although protein content in this fraction was <1% of total cellular protein; iii) this fraction contained c-Src, Rho A, and FAK, but not H-Ras; iv) c-Src and Rho A were co-immunoprecipitated with DSGG through anti-DSGG mAb RM2 (IgM) affixed to a column. These observations indicate that DSGG is clustered in RCC, as typified by TOS-1 cells, to form a microdomain in which it is closely associated with c-Src, Rho A, and FAK, and may constitute a functional unit as has been observed for GM3 with transducer molecules in B16 cells. The functional organization of such units may be essential in determining malignant properties of RCC cells.

Carcinoma, Renal Cell↗

PubMed2000

[Reliability of electrogustatory threshold--electrogustometry using CNV].

CNV (contingent negative variation), an event-related potential, is induced when an oncoming imperative stimulus (S2) is anticipated after recognition of a warning stimulus (S1). With this in mind, we assessed the usefulness of electrogustometry using CNV as an objective gustatory test with an electric gustatory stimulus as a warning stimulus, S1. A gustatory test was performed on a total of 100 sides of the tongue in 50 subjects. Excluding no response cases on 5 sides in 5 subjects, the CNV threshold was successfully determined on 95 sides in 50 subjects. When the CNV threshold values obtained and the conventionally measured subjective threshold values were compared, a very high correlation was demonstrated between the two thresholds, with a correlation coefficient of 0.961. To assess the reliability of the CNV threshold, three additional measurements on 5 sides in 5 subjects with normal subjective threshold values were performed on different days, and the CNV threshold value variation among the three measurements in all 5 subjects never exceeded 13 microA. Separately, subjective threshold and CNV threshold values were compared in 4 patients with facial palsy (hence with gustatory abnormality) who consented to a follow-up examination. The difference between the subjective threshold and CNV threshold values in all 4 patients never exceeded 10 microA. These findings demonstrate that the reliability of the CNV threshold is satisfactory. Next, a gustatory imitation experiment was performed to assess the usefulness of electrogustometry using CNV as a means of detecting gustatory abnormality malingering. The experiment was performed on a total of 6 subjects: 3 physicians with knowledge of CNV (knowledge group) and 3 others with no knowledge of CNV (no-knowledge group). The differences between the imitated threshold and the subjective threshold values in all of these subjects never exceeded 10 microA, and the difference between imitated threshold and CNV threshold values never exceeded 13 microA. Comparison between the knowledge group and the no-knowledge groups showed that the imitated threshold values were very close to the subjective threshold and CNV threshold values. Based on the above results, it was concluded that gustometry using CNV is useful and can serve well as a method of objective evaluation of gustatory sensation. The results also suggested that it will be useful in diagnosing malingering.

Adolescent↗

PubMed2000

Pharmacokinetic consideration on administration regimen of lamivudine in japanese patients infected with HIV-1.

OBJECTIVE: The typical regimen for lamivudine is 150 mg bis in die (bid). However, pharmacokinetic values of lamivudine will differ among individual patients. In addition, few studies regarding the pharmacokinetics of lamivudine in the Japanese people have so far been reported. Therefore, we have aimed to examine the variation in the pharmacokinetic values of lamiduvine present in six Japanese patients with HIV-1 infection. PATIENTS AND METHODS: Lamivudine concentrations were measured in three hemophiliacs (HIV-1-asymptomatic carrier, AC) and three non-hemophiliacs (2 of these patients were AC and one had AIDS-related complex, ARC). In order to simulate the lamivudine plasma concentrations found in chronic oral administration, we added an absorption compartment to the two-compartment model. RESULTS: The mean +/- SD of Tmax, Cmax, AUC(0 - infinity) and t1/2beta were 1.2 +/- 0.5 (hours), 1,280 +/- 267 (ng/ml), 6,778 +/- 2,763 (ng x h/ml), and 10.3 +/- 4.7 (hours), respectively. Although these values were comparable on average to those previously reported, there were noticeable differences with respect to the various time courses of drug plasma concentration among each patient. CONCLUSION: Computations speculated that the trough and peak plasma concentrations as well as the AUC at steady-state change significantly depending on each patient. It suggests that individual pharmacokinetic values of lamivudine should be determined before deciding the optimal administration dose for specific patients.

Adult↗

PubMed2000

Structure determination and total synthesis of a novel antibacterial substance, AB0022A, produced by a cellular slime mold.

A novel antibacterial substance, AB0022A, was isolated from the cellular slime mold Dictyostelium purpureum K1001. It inhibited the growth of Gram-positive bacteria, and its MICs ranged from 0.39 to 50 microg/ml. Because AB0022A was a highly substituted aromatic compound, we could not determine its structure based on only its physico-chemical and spectral data. We therefore used a dehalogenated derivative from AB0022A and deduced that its structure was 1,9-dihydroxy-3,7-dimethoxy-2-hexanoyl-4,6,8-trichlorodibenzofuran . To confirm this structure, we synthesized the compound having the deduced structure. The synthetic compound was identical to naturally occurring AB0022A.

Animals↗

PubMed2000

A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts.

OBJECTIVE: Flavonoids including nobiletin are known to exert many biological actions in vitro. We investigated the chondroprotective effect of citrus flavonoids, especially nobiletin, using cultured rabbit synovial fibroblasts and articular chondrocytes. METHODS: We examined the effects of citrus flavonoids on the production and gene expression of matrix metalloproteinases (MMP) and prostaglandin E2 (PGE2)production in rabbit synovial fibroblasts. RESULTS: Six flavonoids isolated from Citrus depressa Rutaceae including tangeretin, 6-demethoxytangeretin, nobiletin, 5-demethylnobiletin, 6-demethoxynobiletin, and sinensetin suppressed the interleukin 1 (IL-1) induced production of proMMP-9/progelatinase B in rabbit synovial cells in a dose dependent manner (<64 microM); nobiletin most effectively suppressed proMMP-9 production along with the decrease in its mRNA. Nobiletin also reduced IL-1 induced production of PGE2 in the synovial cells, but did not modify the synthesis of total protein. These suppressive effects of nobiletin were also observed in rabbit articular chondrocytes. Nobiletin inhibited proliferation of rabbit synovial fibroblasts in the growth phase. CONCLUSION: These results suggest nobiletin is a novel antiinflammatory candidate that has the potential to inhibit PGE2 production, matrix degradation of the articular cartilage, and pannus formation in osteoarthritis and rheumatoid arthritis.

Animals↗