Hand-assisted laparoscopic splenectomy in ABO-incompatible kidney transplant recipients: a single skin incision technique.
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ABO Blood-Group System↗
Biomedical subjects
K Kai
Publications and source records attributed to K Kai.
Expression of cathepsin L in normal endometrium and endometrial cancer.
OBJECTIVE: To evaluate the expression of cathepsin L in normal endometrium and endometrial adenocarcinoma. STUDY DESIGN: Tissue from eight cases of G1 and eight of G2 endometrioid adenocarcinoma, and 15 normal endometrial specimens were examined by immunohistochemistry. RESULTS: In the normal endometrium, cathepsin L was expressed in a few cell layers of the apical part of the glandular epithelium throughout the menstrual cycle. In the carcinomas, there was an inverse correlation between the grade of tumor and the cathepsin L expression. CONCLUSION: Cathepsin L expression may cease during endometrial carcinogenesis and its expression may be less important in tumor progression than it is in tumors of other tissues.
Adenocarcinoma↗
Expression of epithelial neutrophil-activating peptide 78 in cultured human endometrial stromal cells.
It has been demonstrated that human endometrial stromal cells (ESC) produce a variety of chemokines in vivo and in vitro. To evaluate the expression of epithelial neutrophil-activating peptide 78 (ENA-78) in the endometrium, concentrations of ENA-78 in cyclic endometrial tissues were measured using enzyme-linked immunosorbent assay. The expression of ENA-78 was also detected in cyclic endometrium by immunohistochemistry. Endometrial tissues in the secretory phase contained higher amounts of ENA-78 protein than did those in the proliferative phase. Immunofluorescence staining revealed that ENA-78 protein was localized mainly in the stroma of endometrium. In addition, to evaluate the involvement of inflammatory mediators and ovarian steroid hormones in the production of ENA-78 by ESC was evaluated by in-vitro studies. Unstimulated ESC constitutively secreted ENA-78. Progesterone, lipopolysaccharide, tumour necrosis factor-alpha, and interleukin-1beta significantly stimulated the expression of ENA-78 by ESC. It is suggested that the production of ENA-78 by ESC is regulated by progesterone as well as by the inflammatory mediators. The modulation of ENA-78 concentration in the local environment by these mediators may contribute to the normal and pathological processes of human reproduction through regulation of leukocyte trafficking into the endometrium.
Cells, Cultured↗
Expression and regulation of growth-regulated oncogene alpha in human endometrial stromal cells.
Growth-regulated oncogene alpha (GROalpha), a potent chemoattractant for neutrophils, has previously been detected in the endometrial stromal cells (ESC) of human endometrium. In this study, the mRNA expression of GROalpha in the endometrium was evaluated by reverse transcription-polymerase chain reaction analysis, while the localization of GROalpha protein was studied by immunohistochemistry and the concentrations of GROalpha were measured using an enzyme-linked immunosorbent assay (ELISA). The effects of known modulators of endometrial function on the production of GROalpha by ESC were also examined by ELISA and Northern blot analysis. The expression of both GROalpha mRNA and GROalpha protein was detected in the cycling endometrium. GROalpha protein was localized mainly in the stroma, and endometrial tissues in the secretory phase contained higher amounts of GROalpha protein than did those in the proliferative phase. The production of GROalpha by ESC was enhanced by in-vitro decidualization. Lipopolysaccharide, tumour necrosis factor-alpha and interleukin-1beta also stimulated the expression of GROalpha mRNA and protein by ESC. These results suggest that the production of GROalpha by ESC is regulated by ovarian steroid hormones as well as by inflammatory mediators. The modulation of GROalpha concentrations in the local environment may contribute to normal and pathological processes in the uterus by regulating leukocyte trafficking in the endometrium.
Cells, Cultured↗
Mizoribine ameliorates the tubulointerstitial fibrosis of obstructive nephropathy.
Mizoribine has been shown to possess an immunosuppressive action that inhibits the proliferation of lymphocytes selectively by interfering with inosine monophosphate dehydrogenase. Recent studies have demonstrated that mizoribine improves renal tubulointerstitial fibrosis in the rat model of unilateral ureteral obstruction (UUO) by inhibiting the infiltration of macrophages. We, therefore, examined the dose dependency of the suppressive effect of mizoribine on the infiltration of interstitial macrophages and T lymphocytes and the interstitial volume in UUO-treated kidneys. Furthermore, we investigated the expression of osteopontin (OPN), known to be a chemoattractant protein for macrophages, in the renal cortex. In rats with UUO, the interstitial volume was markedly expanded, and macrophage and T lymphocyte infiltration in the interstitium and the expression of OPN in the cortical tubules were greatly increased. Treatment with mizoribine ameliorated the increase in interstitial volume induced by UUO. Interstitial infiltration of macrophages and T lymphocytes was dose dependently suppressed by mizoribine, and the decreased macrophage infiltration was correlated with inhibition of tubular OPN expression. These results suggest that mizoribine has a beneficial effect on several steps contributing to the progression of tubulointerstitial fibrosis caused by obstruction of the ureter.
Animals↗
Isolation and characterization of Desulfitobacterium sp. strain Y51 capable of efficient dehalogenation of tetrachloroethene and polychloroethanes.
A strict anaerobic bacterium, strain Y51, was isolated from soil contaminated with tetrachloroethene (PCE). Strain Y51 is capable of very efficiently dehalogenating PCE via trichloroethene (TCE) to cis-1,2-dichloroethene (cis-1,2-DCE) at concentrations as high as 960 microM and as low as 0.6 microM. Strain Y51 was gram-negative, motile with some lateral flagella, and curved rod-shaped. On the basis of the 16S rDNA sequence, the organism was identified to be a species within the genus Desulfitobacterium. Strain Y51 also had dehalogenation activities toward polychloroethanes such as hexa-, penta-, and tetrachloroethanes, from which dichloroethenes were produced as the final products. The cell extracts mediated the dehalogenation of PCE with reduced methyl viologen as an electron carrier at the specific rate of 5.0 nmol min(-1) mg cell protein(-1) (pH 7.2, 37 degrees C). Dehalogenation was highly susceptible to air oxidation, and to potential alternative electron acceptors such as nitrite or sulfite.
Bacillaceae↗
Uncoupling between bone formation and resorption in ovariectomized rats with chronic cadmium exposure.
Osteoporosis, osteomalacia, and pathological fractures are characteristic features of Itai-Itai disease. The mechanisms of bone damage caused by cadmium (Cd) exposure have not been fully clarified. We investigated skeletal changes in ovariectomized rats with chronic Cd exposure, using bone histomorphometry and mechanical tests. Female Sprague-Dawley rats at the age of 8 weeks were ovariectomized. Eight weeks after ovariectomy, the rats were divided into two groups: Cd-OVX group (n = 15), ovariectomized rats given cadmium chloride (CdCl(2), 0.18 mg/rat) ip three times a week for 28 weeks; Cont-OVX group (n = 10), ovariectomized rats given distilled water alone for 28 weeks. Cd-OVX rats had a significant increase in serum concentration of intact osteocalcine and showed numerical but not significant increase in urinary excretion of deoxypyridinoline despite a significant decrease in glomerular filtration rate to 40% of the value in Cont-OVX rats. Bone mineral content (BMC) and density were significantly decreased in both the lumbar vertebral body and femur of Cd-OVX rats. Ultimate compressive load in the lumbar body and bending load in the midfemur were significantly lower in Cd-OVX rats than in Cont-OVX rats but the differences were not demonstrated when the values were corrected for BMC. Structural moduli in the lumbar vertebral body and the midfemur were not different between the two groups. Cd-OVX rats showed significant decreases in the trabecular bone volume and trabecular number with increased values in the indices of bone formation and resorption in the lumbar vertebral body cancellous bone in comparison with Cont-OVX rats. In the midfemur, Cd-OVX rats had significantly smaller cortical bone area than Cont-OVX rats but the moment of inertia was identical between the two groups. The indices of bone formation and resorption at endocortical surface of the midfemur were significantly increased in Cd-OVX rats over those in Cont-OVX rats, whereas the indices of bone formation at the periosteal surface were not different between the two groups. These data suggested that chronic Cd exposure exacerbated the uncoupling between bone formation and resorption in ovariectomized rats, which resulted in the osteopenia, structural changes of the bone, and decreased mechanical strength in ovariectomized rats with chronic Cd exposure.
Amino Acids↗
Environmental stress modifies glycemic control and diabetes onset in type 2 diabetes prone Otsuka Long Evans Tokushima Fatty (OLETF) rats.
This study was designed to investigate the effects of environmental stress on metabolic derangements and the expression of diabetes phenotype in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human type 2 diabetes (NIDDM). Acute environmental stress, i.e., exposure to water with immobilization for 1 h, caused a transient increase in blood glucose with decreased insulin secretion, and the stress-induced hyperglycemia augmented with age. The increased glycemia was associated with increased plasma levels of catecholamines and corticosterone. Short-term stress, the same stress of 1 h/day for 10 days, caused a significant decrease of food intake, which led to weight reduction in OLETF rats, aged 50 weeks. Blood glucose and insulin responses in OGTT showed no change before or after the short-term stress, despite the weight reduction. In chronic stress experiments, i.e., exposure to the same kind of stress for 6 days/week from 8 to 75 weeks of age, stressed rats did not gain weight, compared to control rats. Blood HbA1c levels and the index of insulin resistance after a 4-h unfed period were significantly lower in stressed rats than in controls from 35 and 45 weeks of age on, respectively. The occurrence of diabetes, diagnosed by OGTT, was also significantly lower in the rats subjected to chronic stress than in controls. These results suggest that chronic stress from 8 weeks of age inhibited weight gain, probably due to changes in eating behavior, preventing the deterioration of insulin resistance in OLETF rats. Plasma leptin levels were not modulated by stress, and correlated with body weight in the rats under chronic stress and in controls. These results suggest that in type 2 diabetes, blood glucose derangement due to stress is presumably associated not only with changes in counterregulatory hormones involved in glucose metabolism, but also with stress-induced changes in eating behavior.
Animals↗
At least four non-env factors that reside in the LTR, in the 5'-non-coding region, in gag and in part of pol affect neuropathogenicity of PVC-441 murine leukemia virus (MuLV).
PVC-441 murine leukemia virus (MuLV) is neuropathogenic in F344 rats. Recently, an infectious DNA clone was isolated and its nucleotide sequence was determined (J. Virol. 72: 3423-3426. 1998). To identify the viral determinants of neuropathogenicity of the molecularly cloned PVC-441 MuLV, chimeras were constructed between PVC-441 MuLV and F-MuLV clones at appropriate restriction enzyme sites that divide the viral genome approximately in LTR-non-coding, gag-, pol-, and env-gene regions. Results indicated that the LTR-non-coding and the gag-gene regions of PVC-441 MuLV affected independently the neuropathogenicity in combination with the env gene region as evidenced clinically and pathologically. Studies on the distribution of vacuolar degeneration suggested that the pons and cervical spinal cord areas were the primary targets and the large brain was the latest target of PVC-441 MuLV. Further studies with chimeric viruses that were formed in the LTR-non-coding and the gag gene regions revealed that at least four factors affected the neuropathogenicity of PVC-441 MuLV. Two factors were found in the U3, and R-U5-5'-non-coding regions, and at least two factors in the gag gene region that contained the N-terminal part of the pol gene. Among these factors, at least two factors seemed to be 'cis-acting' from each other
5' Untranslated Regions↗
Skeletal changes in rats bearing mammosomatotrophic pituitary tumors: a model of acromegaly with gonadal dysfunction.
Growth hormone (GH) exerts potent effects on bone metabolism, resulting in an increased bone formation in animals and humans. Acromegaly has been associated with increased bone turnover, whereas the net effect of the increased bone metabolism has been obscured because patients with acromegaly are often associated with hypogonadism. We investigated changes in cortical and cancellous bone in adult rats implanted mammosomatotrophic pituitary tumor cells (GH3) as a model of acromegaly with gonadal dysfunction. Acromegaly model rats were prepared by implanting GH3 cells into female Wistar-Furth rats at 17 weeks of age. At 28 weeks of age, GH3-bearing rats (GH rats) showed very high serum GH levels and a moderate increase in serum prolactin levels, resulting in low circulating estradiol levels. The GH rats showed significant increases in body weight and in length and volume of both the femur and vertebral body. Bone mineral content values of either the midfemur or the whole lumbar body were significantly greater in the GH rats compared with littermate controls, while the areal bone mineral density values of the respective bones were not different between the two groups. The parameters of mechanical strength of the femur were significantly larger in the GH rats than in controls, whereas those of the lumbar vertebral body cylinder specimen were not different between the two groups. Respective normalized mechanical parameters of the femur and the vertebral body were the same in the GH rats as in controls. In the midfemur, the GH rats showed a significant increase in the total cross-sectional area without influencing the bone marrow area, resulting in an increase in the cortical bone area and the moment of inertia compared with controls. The indices of periosteal bone formation in the midfemur were greater in the GH rats compared with controls, but the endocortical bone formation and resorption were not different between the two groups. In the vertebral body cancellous bone, the GH rats had an increase in bone turnover rate, whereas the structural parameters were not different between the two groups. These results from GH3-bearing rats demonstrate that an excess of GH increases cortical bone mass in rats accompanied with estrogen deficiency, while no large effect on vertebral body cancellous bone mass is seen.
Acromegaly↗
Adherence of Fusobacterium necrophorum subsp. necrophorum to ruminal cells derived from bovine rumenitis.
Fusobacterium necrophorum subsp. necrophorum strain VPI 2891 was shown to adhere to the surfaces of ruminal cells derived from bovine rumenitis. The strain also attached to bovine type 1 collagen. Treatment of the bacterium with antiserum to bacterial cells reduced attachment. The bacterial attachment was also markedly reduced when the ruminal cells had been pretreated with anticollagen serum. Fluorescence specific for the collagen was demonstrated on the surface of bovine tissue affected with rumenitis. These findings suggest that F. necrophorum subsp. necrophorum strain VPI 2891 adheres to the ruminal cells derived from rumenitis tissue and that the attachment may be mediated by cellular collagen.
Animals↗
Centrally administered murine-leptin stimulates the hypothalamus-pituitary- adrenal axis through arginine-vasopressin.
Starvation induces a decrease in circulating leptin levels and activation of the hypothalamus-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis in unfed rodents or genetically leptin-deficient ob/ob mice, whereas it stimulates corticotropin-releasing hormone (CRH) gene expression in the paraventricular nucleus (PVN). However, the interactions between leptin, CRH and the HPA axis are poorly understood and are likely to be complex. We recently demonstrated that central leptin administration caused increases in plasma arginine-vasopressin (AVP) and AVP gene expression of the PVN in nonstressful rats. AVP stimulates the release of adrenocorticotropic hormone (ACTH), but it also potentiates the action of CRH on ACTH release. In this study, we investigated the effects of leptin on plasma ACTH and corticosterone levels, CRH mRNA of the PVN and proopiomelanocortin (POMC) mRNA of the pituitary in nonstrained rats. Intracerebroventricularly administered leptin caused increases in plasma ACTH and corticosterone levels in dose-dependent manners. In Northern blot analyses, the leptin injection induced significant increases in the expression of CRH mRNA in the PVN and POMC mRNA in the pituitary. The increased plasma ACTH and corticosterone levels by leptin were attenuated with intracerebroventricular pretreatment of a V(1a) receptor antagonist (OPC-21268) or a V(1a)/V(1b) receptor antagonist (dP[Tyr(Me)(2)]AVP), but not with that of a V(2) receptor antagonist (OPC-31260). The leptin-induced CRH mRNA expression in the PVN and POMC mRNA expression in the pituitary were also reduced by the pretreatment with OPC-21268 and dP[Tyr(Me)(2)]AVP. These results suggest that intracerebroventricular leptin administration activates the HPA axis by AVP receptor activation through V(1a) receptors in the PVN which in turn activates CRH neurons to drive ACTH and corticosterone secretion in concert with AVP in nonstrained rats.
Adrenocorticotropic Hormone↗
Application of a type-specific enzyme-linked immunosorbent assay for equine herpesvirus types 1 and 4 (EHV-1 and -4) to horse populations inoculated with inactivated EHV-1 vaccine.
A type-specific enzyme-linked immunosorbent assay (ELISA) using equine herpesvirus types 1 (EHV-1) and 4 (EHV-4) glycoprotein G was applied for sero-epizootiology of EHV infections in Japan. Recently, an inactivated EHV-1 vaccine has been administered to racehorses for prevention of upper respiratory disease. To examine the effect of the vaccination on the result of the ELISA, 6 horses were experimentally inoculated three times intramuscularly or intranasally with inactivated EHV-1 vaccine. Sera collected from these horses were used to the type-specific ELISA and complement-fixation (CF) test. Although the CF test detected a significant increase of antibody elicited by vaccination, the ELISA did not detect any antibody response. Next, sera collected from thirty-eight horses, which were intramuscularly inoculated with inactivated EHV-1 twice at an interval of four weeks, were used in the ELISA and CF test. The results also indicated that CF titers increased by vaccine inoculation, but ELISA titers did not. To examine epizootiology of EHVs serologically in racehorse populations at two Training Centers of the Japan Racing Association, the type-specific ELISA and CF test were carried out using paired sera collected from racehorses before and after the winter season. The results showed that the ELISA could distinguish EHV-1 and EHV-4 infections in vaccinated horses serologically. In conclusion, the type-specific ELISA is considered to be useful for sero-diagnosis and sero-epizootiological research on EHV-1 and EHV-4 infections not only in unvaccinated horses, but also in vaccinated horses in Japan.
Administration, Intranasal↗
Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 27). Repeated toxicity study on ethylene glycol monomethyl ether for 2 and 4 weeks to detect effects on male reproductive organs in rats.
As part of a collaborative project to determine the minimum administration period to detect compound effects on male reproductive organs in Sprague-Dawley (Crj:CD(SD)) male rats, 6- and 8-week-old rats were administered ethylene glycol monomethyl ether (EGME) daily at 100 and 200 mg/kg/day for 2 weeks or 100 mg/kg/day for 4 weeks, and histopathological changes in the testes and epididymides were examined. Testis and epididymis weights in the 2-week 200 mg/kg and 4-week 100 mg/kg groups were obviously decreased. On histopathological examination, severe degenerative changes in the testis such as atrophy of the seminiferous tubules and multinucleated giant cell formation were observed in all 2-week 200 mg/kg group rats. Degeneration of pachytene spermatocytes in Stages X IV-II, III and a decrease in the number of germ cells was observed with both 2 and 4 weeks treatments at 100 mg/kg/day. In the epididymides, the number of sperm in the caput decreased with 100 mg/kg/day groups after both 2 and 4 weeks. In addition, degeneration of pachytene spermatocytes induced by EGME was found to be exclusively due to apoptotic death. Similar testicular and epididymal changes were observed with 2 and 4 weeks treatments at 100 mg/kg/day of EGME. Therefore, we conclude that a 2 weeks administration period is sufficient for detection of EGME effects on male reproductive organs.
Administration, Oral↗
[Respiratory function impairment in patients with Parkinson's disease--a consideration on the possible pathogenetic relation to autonomic dysfunction].
To investigate the characteristics and clinical significance of respiratory function in patients with Parkinson's disease (PD), we studied 38 patients (male, 19; female, 19: mean age, 65.5 years: mean duration of disease, 6.7 years) who had no history of respiratory disease and smoking. Fifty three non-respiratory disease subjects (male, 26; female, 27: mean age, 67.6 years) were served as age-matched control. We measured spirometry and maximal expiratory flow-volume curve in all patients, and analyzed the relations between respiratory function variables and clinical profiles. The clinical disability of PD was indicated by Hoehn-Yahr (H-Y) scale. The number of PD patients was 15 in H-Y 2, 18 in H-Y 3 and 5 in H-Y 4, respectively. The values of % VC, %FEV 1, FEV 1/FVC, %PEFR, % V50 in H-Y 4 group were significantly smaller than those in H-Y 2 and 3 groups. Small airway dysfunction (SAD) was represented by abnormality of % V25, % V50/V25. The prevalence of impairment in % V25 and % V50/V25 was detected in 13 patients (34.2%) and 15 patients (39.5%), respectively, this was significantly higher than age-matched controls. However, the mean value and prevalence of impairment in % V25, % V50/V25 were not affected by H-Y scale and duration of disease or ideal body weight (%predicted value). Twenty seven patients showed normal ventilatory function based on % VC over 80% and FEV 1/FVC over 70%. The prevalence of impairment in % V25, % V50/V25 was detected in 8 patients (29.6%), 9 patients (33.3%), respectively, among 27 patients with normal ventilatory function. These results suggest that ventilatory dysfunction is concerned with clinical disability but SAD which is independent of clinical disability seen prevalently in patients with PD. It is widely accepted that patients with PD frequently have cardiac or bowel dysfunction based on the visceral autonomic dysfunction. We hypothesize that SAD may also be caused by possible autonomic dysfunction in patients with PD.
Aged↗
Renal hemodynamics in Otsuka Long-Evans Tokushima fatty rat, a model rat of spontaneous non-insulin-dependent diabetes mellitus with obesity.
Renal hemodynamic features in obese non-insulin-dependent diabetic rats remain unknown. We investigated renal hemodynamic and morphologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age of 5 and 10 months compared with age-matched lean nondiabetic control rats (LETO). OLETF rats showed obesity compared with age-matched LETO rats. Hyperglycemia was mild in 5-month-old OLETF rats and moderate in 10-month-old OLETF rats. The absolute value for glomerular filtration rate (GFR) was significantly higher in OLETF rats than in age-matched LETO rats at the age of 5 and 10 months. Ten-month-old OLETF rats had significantly higher absolute values for renal plasma flow (RPF) than age-matched LETO rats but not 5-month-old OLETF rats. Stepwise multiple regression analysis revealed that body weight was a powerful determinant of GFR and RPF. When factored for body weight, no difference in GFR was demonstrated between 5-month-old OLETF and LETO rats, whereas 10-month-old OLETF rats still had significantly higher GFR and RPF than age-matched LETO rats. Renal hypertrophy was demonstrated in both 5- and 10-month-old OLETF rats even when factored for body weight. Glomerular volume was significantly increased in 10-month-old OLETF rats, but the ratio of glomerular volume to body weight was not different among the groups. Both absolute value for glomerular capillary length free from mesangial area and the value factored for glomerular area were significantly longer in OLETF rats than in age-matched LETO rats. Mesangial matrix expansion was remarkable in 10-month-old OLETF rats, and the glomerular sclerosis index was significantly higher in 10-month-old OLETF rats than in age-matched LETO rats. Stepwise multiple regression analysis revealed that body weight, hemoglobin A1c, and hypertriglyceridemia were powerful determinants for kidney weight and glomerular volume. These data suggest that renal hyperfiltration and hypertrophy observed in 10-month-old OLETF rats are related to diabetic metabolic disorders and that obesity-related conditions may be involved in the renal hemodynamic and morphologic features in OLETF rats.
Animals↗
Culture of human parathyroid cells for transplantation.
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Antigens, CD↗
Enhancement by galactosamine of lipopolysaccharide(LPS)-induced tumour necrosis factor production and lethality: its suppression by LPS pretreatment.
1. D-Galactosamine (GalN) depletes UTP primarily in the liver, resulting in decreased RNA synthesis in hepatocytes. Co-injection of GalN and lipopolysaccharide (LPS) into mice produces fulminant hepatitis with severe hepatic congestion, resulting in rapid death. Although the underlying mechanism is uncertain, GalN enhances the sensitivity to tumour necrosis factor (TNF). Administration of uridine (a precursor of UTP) prior injection of either LPS itself or interleukin-1 (IL-1) reduces the lethality of GalN+LPS. The present study focused on the effects of these agents on TNF production. 2. Intraperitoneal injection of GalN+LPS into mice greatly elevated serum TNF. Although large doses of LPS alone also greatly elevated serum TNF, LPS itself induced neither hepatic congestion nor rapid death. Administration of a macrophage depletor, liposomes encapsulated with dichloromethylene bisphosphonate, reduced both the TNF production and mortality induced by GalN+LPS. 3. Uridine, when injected 0.5 h after the injection of GalN+LPS, reduced the production of TNF. Prior injection of LPS, but not of IL-1, also reduced this TNF production. 4. Serum from LPS-injected mice reduced the TNF production induced by GalN+LPS, but it was less effective at reducing the lethality. Its ability to reduce TNF production was abolished by heat-treatment. 5. We hypothesize that a factor inhibiting TNF production by macrophages is produced by hepatocytes in response to LPS. Possibly, production of this hepatocyte-derived TNF-down-regulator (TNF-DRh) may be: (i) inhibited by GalN, causing over-production of TNF by macrophages and (ii) stimulated by LPS-pretreatment (and restored by uridine), causing reduced TNF production.
Animals↗