Biomedical subjects

Y Cui

Publications and source records attributed to Y Cui.

At least 109 records · Page 6Linked to original sources

PubMed2000

ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2.

BACKGROUND: Para-aminohippurate (PAH), a widely used model substrate for organic anion transport in proximal tubule epithelia, was investigated as a substrate for the apical multidrug resistance protein MRP2 (symbol ABCC2). This ATP-dependent export pump for anionic conjugates and additional amphiphilic anions was cloned recently and localized to the apical membrane of proximal tubules in human and rat kidney. METHODS: Membrane vesicles from HEK-MRP2 cells containing recombinant human MRP2 and from control vector-transfected HEK-Co cells were incubated with various concentrations of [3H]PAH, and the net ATP-dependent transport into inside-out vesicles was determined. Comparative studies were performed with membrane vesicles containing recombinant human MRP1. RESULTS: Transport rates at 10 micromol/L PAH were 21.9 +/- 1.9 and 1.6 +/- 0.4 pmol x mg protein-1 x min-1 (means +/- SEM, N = 10) with membrane vesicles from HEK-MRP2 and HEK-Co cells, respectively. The Km value for PAH was 880 micromol/L. The high-affinity substrate leukotriene C4 and the inhibitor of MRP-mediated transport, MK571, inhibited MRP2-mediated transport of PAH (100 nmol/L) with IC50 values of 3.3 and 4.0 micromol/L, respectively. The nephrotoxic mycotoxin ochratoxin A inhibited MRP2-mediated PAH transport with an IC50 value of 58 micromol/L. Ochratoxin A was itself a substrate for MRP2. CONCLUSIONS: PAH is a good substrate for the ATP-dependent export pump MRP2. The localization and function of MRP2 indicate that this unidirectional transport protein contributes to the secretion of PAH and other amphiphilic anions into the lumen of kidney proximal tubules.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2000

Expression of decorin, biglycan, and collagen type I in human renal fibrosing disease.

BACKGROUND: The extracellular matrix proteoglycans decorin and biglycan may have a pathogenic role in renal fibrosing disease via regulation of the activity of growth factors, such as transforming growth factor-beta, and effects on collagen type I fibrillogenesis. The expression of decorin and biglycan in human glomerular diseases characterized by mesangial sclerosis is unknown. METHODS: Decorin, biglycan, and collagen type I were localized immunohistochemically in human renal biopsy cases of amyloidosis (N = 18), diabetic nephropathy (N = 11), fibrillary glomerulonephritis (N = 5), immunotactoid glomerulopathy (N = 5), light-chain deposition disease (N = 4), idiopathic mesangial sclerosis (N = 4), and nephrosclerosis (N = 6), and in morphologically normal tissues obtained from tumor nephrectomies (N = 8). Decorin and biglycan mRNA synthesis was evaluated by in situ hybridization. RESULTS: Decorin and biglycan protein were not identified in normal glomeruli. Decorin accumulated in amyloid deposits, but not in deposits of fibrillary glomerulonephritis or immunotactoid glomerulopathy. Biglycan weakly accumulated in amyloid deposits, and both decorin and biglycan weakly stained mesangial nodules in cases of morphologically advanced light-chain deposition disease and diabetic nephropathy. In all analyzed cases, irrespective of the underlying disease, decorin and biglycan accumulated in glomeruli in areas of fibrous organization of the urinary space and in areas of tubulointerstitial fibrosis. Biglycan, but not decorin, accumulated in the neointima of arteriosclerotic blood vessels. Decorin and biglycan mRNA synthesis was detected at sites of proteoglycan accumulation in glomeruli, interstitium, and neointima. Collagen type I colocalized with decorin and biglycan deposits. CONCLUSIONS: Differences in extracellular matrix proteoglycan composition may be diagnostically useful in distinguishing morphologically similar diseases. Distinct patterns of proteoglycan expression may be related to modulation of specific growth factor activity in different glomerular diseases.

Amyloidosis↗

PubMed2000

Nitric oxide synthase inhibition negates bombesin-induced gastroprotection.

BACKGROUND: Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. METHODS: Rats were given subcutaneous saline or bombesin (10-100 microg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm(2)). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. RESULTS: Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) l-arginine (300 mg/kg), but not d-arginine, abolished the effects of l-NAME. CONCLUSIONS: Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.

Administration, Oral↗

PubMed2000

Two mixed-metal carboxylate-base adducts

The crystal structures of hexa-&mgr;-propionato-1:2kappa(6)O:O';1:3kappa(6)O:O'-diquinoline-2ka ppaN,3kappaN-calcium(II)dizinc(II), [CaZn(2)(C(3)H(5)O(2))(6)(C(9)H(7)N)(2)], and hexa-&mgr;-pivalato-1:2kappa(6)O:O';1:3kappa(6)O:O'-diquinoline-2kapp aN,3kappaN-calcium(II)dicobalt(II), [CaCo(2)(C(5)H(9)O(2))(6)(C(9)H(7)N)(2)], are described. Both contain a linear array of one Ca(II) ion and two M(II) (M = Zn, Co) ions connected by two sets of three carboxylate ligands in syn-syn bridging modes. The distorted tetrahedral geometry around the M(II) ion is completed by a quinoline N atom. The central Ca(II) ion occupies a crystallographic inversion centre and is octahedrally coordinated by six carboxyl O atoms in each structure. The Zn(II). Ca(II) and Co(II).Ca(II) distances are 3.8504 (9) and 3.7929 (5) A, respectively.

Journal Article↗

PubMed2000

Sch-28080 depletes intracellular ATP selectively in mIMCD-3 cells.

Two H(+)-K(+)-ATPase isoforms are present in kidney: the gastric, highly sensitive to Sch-28080, and the colonic, partially sensitive to ouabain. Upregulation of Sch-28080-sensitive H(+)-K(+)-ATPase, or "gastric" H(+)-K(+)-ATPase, has been demonstrated in hypokalemic rat inner medullary collecting duct cells (IMCDs). Nevertheless, only colonic H(+)-K(+)-ATPase mRNA and protein abundance increase in this condition. This study was designed to determine whether Sch-28080 inhibits transporters other than the gastric H(+)-K(+)-ATPase. In the presence of bumetanide, Sch-28080 (200 microM) and ouabain (2 mM) inhibited (86)Rb(+) uptake (>90%). That (86)Rb(+) uptake was almost completely abolished by Sch-28080 indicates an effect of this agent on the Na(+)-K(+)-ATPase. ATPase assays in membranes, or lysed cells, demonstrated sensitivity to ouabain but not Sch-28080. Thus the inhibitory effect of Sch-28080 was dependent on cell integrity. (86)Rb(+)-uptake studies without bumetanide demonstrated that ouabain inhibited activity by only 50%. Addition of Sch-28080 (200 microM) blocked all residual activity. Intracellular ATP declined after Sch-28080 (200 microM) but recovered after removal of this agent. In conclusion, high concentrations of Sch-28080 inhibit K(+)-ATPase activity in mouse IMCD-3 (mIMCD-3) cells as a result of ATP depletion.

Adenosine Triphosphate↗

PubMed2000

A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane.

We cloned and expressed a new organic anion transporting polypeptide (OATP), termed human OATP2, (OATP-C, LST-1; symbol SLC21A6), involved in the uptake of various lipophilic anions into human liver. The cDNA encoding OATP2 comprised 2073 base pairs, corresponding to a protein of 691 amino acids, which were 44% identical to the known human OATP. An antibody directed against the carboxy terminus localized OATP2 to the basolateral membrane of human hepatocytes. Northern blot analysis indicated a strong expression of OATP2 only in human liver. Transport mediated by recombinant OATP2 and its localization were studied in stably transfected Madin-Darby canine kidney strain II (MDCKII) and HEK293 cells. Confocal microscopy localized recombinant OATP2 protein to the lateral membrane of MDCKII cells. Substrates included 17beta-glucuronosyl estradiol, monoglucuronosyl bilirubin, dehydroepiandrosterone sulfate, and cholyltaurine. 17beta-Glucuronosyl estradiol was a preferred substrate, with a Michaelis-Menten constant value of 8.2 microM; its uptake was Na(+) independent and was inhibited by sulfobromophthalein, with a inhibition constant value of 44 nM. Our results indicate that OATP2 is important for the uptake of organic anions, including bilirubin conjugates and sulfobromophthalein, in human liver.

Amino Acid Sequence↗

PubMed2000

Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.

Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3'-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders.

Animals↗

PubMed2000

Development of mouse dendritic cells from lineage-negative c-kit(low) pluripotent hemopoietic stem cells in vitro.

Dendritic cells (DCs) are essential for the presentation of antigens in the primary immune response. To examine the generation of DCs from hemopoietic stem cells in the bone marrow (BM), lineage-negative (Lin-)/CD71- bone marrow cells (BMCs) from C57BL/6 mice were separated into major histocompatibility complex (MHC) class Ihigh/ c-kit(low) and MHC class Ihigh/c-kit(low)(phenotypically c-kit-negative, but c-kit message only detected by reverse transcriptase-polymerase chain reaction) populations. A large number of cells with the morphological, phenotypical, and functional characteristics of DCs was generated from both c-kit(low) and c-kit(low) populations when cultured with a combination of cytokines (GM-CSF, tumor necrosis factor-a [TNF-a], interleukin 7 [IL-7], IL-3, stem cell factor [SCF], and flt3 ligand); the cytokine combination studies revealed that SCF and IL-3 in addition to GM-CSF and TNF-a are essential for DCs to be generated from these primitive populations. To our surprise most (>80%) generated cells expressed high levels of DC surface markers such as DEC205 and MHC class II, and they were potent stimulators in the primary allogeneic T cell activation. The development of DCs from c-kit(<low) cells was slower than that from c-kit(low) cells. These results indicate that c-kit(<low) cells are more primitive than c-kit(low) cells, although both c-kit*(low) cells and c-kit(<low) cells can differentiate into DCs. It should be noted that the combination of these cytokines selectively induces DCs from both c-kit(<low) and c-kit(low) cells in vitro, suggesting that the ex vivo expansion of DCs using these primitive cells would be applicable to immunotherapy.

Animals↗

PubMed2000

Latex rubber (Penrose drain) is detrimental to esophagogastric anastomotic healing in rats.

BACKGROUND: Surgeons commonly drain cervical esophagogastric anastomoses, but there is little objective evidence to support this practice. Studies in other areas of gastrointestinal surgery have shown that routine drainage is unnecessary, and even detrimental to anastomotic healing. We conducted an animal experiment to see if a drain had a negative effect on esophagogastric anastomotic healing. METHODS: Esophagogastric anastomoses were done in 40 rats. In the experimental group (20 rats) a portion of latex rubber Penrose drain was placed over the anastomosis. This was not done in the control group (20 rats). Rats were sacrificed 7 days after surgery. The anastomoses were inspected for leaks, distracted in a tensiometer to measure breaking strength, and subjected to hydroxyproline analysis (an indicator of wound collagen). RESULTS: There were 4 contained leaks in the experimental group (drain) and no leaks in the control rats (p=0.033). Anastomotic breaking strength was 3.80+/-0.81 N in the experimental rats and 3.46+/-0.64 N in the control rats (p=0.18, not significant). Anastomotic tissue hydroxyproline concentration was 615.9+/-52 nmol/mg in the experimental rats and 609.4+/-195 nmol/mg in the control rats (p=0.13, not significant). CONCLUSIONS: The presence of drain material predisposed to esophagogastric anastomotic leakage in this rat model.

Anastomosis, Surgical↗

PubMed2000

DNA analysis of a pedigree with myotonic dystrophy in Songjiang county, Shanghai.

OBJECTIVE: To make the molecular analysis of a pedigree with myotonic dystrophy (DM) in Songjiang county, Shanghai, and to observe the connection between CTG repeat number and clinical features. METHODS: In twenty-three individuals of a pedigree with DM, CTG trinucleotide repeat numbers located in the 3' untranslated region of a protein kinase gene (MTPK) on chromosome 19q13.2-3 were analyzed by using Long Expand TM Template PCR system. RESULTS: Four of eight clinical patients had expanded DM allele, the other four had no expanded CTG copies. Seven of eight suspicious DM cases had expanded CTG repeat numbers and were therefore genetically diagnosed as DM, and an asymptomatic individual was diagnosed as a doubted DM patient by DNA analysis. High risk of DM in six of seven individuals was ruled out, and a clinical doubted DM individual was ascertained a normal person by molecular analysis. A positive correlation was found beween early onset and expanded CTG repeat number in six parents (or grandparents)/child pairs, but in the pair II 2 /IV 7 CTG repeat numbers were reduced from 3100 in the grandmother to 175 in her grandson and there was no anticipation phenomenon. CONCLUSION: The measurement of CTG repeat number can help to ascertain the diagnosis of DM in clinical and preclinical patients, but some clinically- diagnosed DM patients might have normal CTG repeat numbers. Anticipation phenomena were common in the pedigree.

Adolescent↗

PubMed2000

cAMP increases the expression of human angiotensinogen gene through a combination of cyclic AMP responsive element binding protein and a liver specific transcription factor.

Angiotensinogen is the glycoprotein precursor of one of the most potent vasoactive hormones angiotensin-II which plays an important role in the regulation of blood pressure. We show here that the promoter activity of reporter constructs containing human angiotensinogen promoter is increased by cAMP treatment on transient transfection in HepG2 cells. We have identified a composite cAMP responsive element, located around 840 bases upstream from the transcriptional initiation site, in the promoter of human angiotensinogen gene. This element is recognized by members of CREB/ATF as well as C/EBP family of transcription factors. Another C/EBP binding site that is not recognized by CREB is located 10 bases upstream from this site. We show that co-transfection of CREB increases the promoter activity of reporter constructs containing human angiotensinogen gene promoter attached to the CAT gene. We also show that co-transfection of DBP (which is a member of C/EBP family of transcription factors) increases promoter activity of these reporter constructs.

Activating Transcription Factor 1↗

PubMed2000

Effect of pyloric drainage on the healing of esophagogastric anastomoses in rats.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks complicate 5% to 20% of esophagectomies for esophageal cancer and are responsible for approximately one-third of perioperative deaths. Poor gastric emptying is a predisposing factor for anastomotic leakage. An animal experiment was used to test the hypothesis that a pyloric drainage procedure (pyloromyotomy) would have a positive effect on esophagogastric anastomotic healing. METHODS: In 40 rats single-layer esophagogastric anastomoses were constructed with interrupted 7-0 polypropylene sutures. A pyloromyotomy was done in the experimental group (20 rats) but not in the control group (20 rats). Rats were sacrificed on the 7th postoperative day and their anastomoses were excised, mounted in a tensiometer, and distracted at 10 mm/min to measure breaking strength. After that, the hydroxyproline concentration (an indicator of wound collagen) of the anastomotic tissue was measured. RESULTS: There were no anastomotic leaks. The mean (and standard deviation) breaking strength of the esophagogastric anastomosis was 3.96 (1.14) N in the pyloromyotomy rats and 4.11 (0.75) N in the control rats (p = 0.64). The mean (and SD) hydroxyproline concentration in esophagogastric anastomotic tissue was 368.6 (31.5) nmol/mg in the pyloromyotomy rats and 376.6 (31.3) nmol/mg in the control rats (p = 0.77). CONCLUSION: Pyloric drainage (pyloromyotomy) did not have any effect on esophagogastric anastomotic wound healing in this rat model.

Anastomosis, Surgical↗

PubMed2000

Omentoplasty reinforcement of esophagogastric anastomoses in rats.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks complicate 5-20% of esophagectomies for esophageal cancer, and they are responsible for approximately one-third of perioperative deaths. Omentoplasty reinforcement has been recommended for esophagogastric anastomoses, but there is little evidence to support this practice. An animal experiment was done to test the hypothesis that omentoplasty reinforcement of esophagogastric anastomoses would have a beneficial effect on healing. METHODS: Twenty-eight rats had single layer esophagogastric anastomoses constructed using interrupted 7-0 polypropylene sutures. In the experimental group (14 rats) the anastomoses were covered with omentum. This was not done in the control group (14 rats). Rats were killed 1 week after surgery and their anastomoses were excised, mounted in a tensiometer, and distracted at 10 mm/min to measure breaking strength. After that, anastomotic tissue was subjected to hydroxyproline analysis (an indicator of wound collagen). RESULTS: There were no anastomotic leaks. Esophagogastric anastomotic breaking strength was 3.45+/-0.63 N in the omentoplasty rats and 3.86+/-0.85 N in the control rats (p=0.24, not significant). Esophagogastric anastomotic tissue hydroxyproline concentration was 388.7+/-33 nmol/mg in the omentoplasty rats and 463.9+/-56 nmol/mg in the control rats (p=0.001). CONCLUSIONS: Omentoplasty reinforcement of esophagogastric anastomoses did not have any beneficial effect on anastomotic healing in this animal experiment.

Anastomosis, Surgical↗

PubMed2000

[Correlation of photoplankton and its environmental factors in Rushan Bay].

The relationship between photoplankton and its environmental factors in Rushan Bay was studied from June to September, 1995. The result shows that there existed a negative correlation between the number of photoplankton and the content of inorganic nutrients. The correlation coefficients for inorganic nitrogen and phosphorus were -0.67 and -0.80, respectively. The dissolved oxygen and chlorophyll-a were positively correlated to photoplankton, and their correlation coefficients were 0.92 and 0.85 respectively. Based on N/P analysis, the content of inorganic nitrogen was relatively short to the reproductive growth of photoplankton during experimental months, except for the last ten days of August.

China↗

PubMed2000

Identification of a mutation hotspot in exon 8 of Wilson disease gene by cycle sequencing.

OBJECTIVE: To screen for mutation hotspot of Wilson disease (WD) gene in Chinese population. METHODS: Cycle sequencing was used to detect mutation in exon 8 of WD gene in 30 patients with Wilson disease. RESULTS: The same missense mutation, Arg779Leu, was identified in 14 WD patients, four of whom were homozygous and the other heterozygous for this mutation. The frequency of this mutation in Chinese patients was 30%. CONCLUSION: The codon 779 (CCG-->CTG) of exon 8 of WD gene was one of mutation hotspots in Chinese.

Adenosine Triphosphatases↗

PubMed2000

[Prevalence of cag A and vac A subtypes of Helicobacter pylori in Guangzhou].

OBJECTIVE: To investigate the prevalence of cytotoxin associated gene (cag A) and vacuolating cytotoxin gene (vac A) subtypes of Helicobacter pylori (Hp) from patients with upper gastrointestinal diseases in Guangzhou, and to assess the relationship between cag A, vac A subtypes and Hp related gastrointestinal diseases. METHODS: 191 Hp strains were isolated from patients with different gastrointestinal diseases in Guangzhou. Bacterial DNA from all these strains was extracted. cag A and vac A alleles were typed using PCR with specific primers. RESULTS: In Guangzhou, Hp cag A positive rate was 85.3% (163/191). cag A positive rate was significantly higher in gastric cancer and peptic ulcer than that in chronic gastritis (P < 0.05). There were six vac A mosaicisms, including 168 for s1a/m2 (88.0%), 14 for s1a/m1b (7.3%), 6 for s1b/m2 (3.1%), 1 for s1b/m1b (0.5%), 1 for s2/m2 (0.5%) and 1 for s1a/m1b-m2 (0.5%). The rate of vac A s1a/m2 subtype in chronic gastritis, peptic ulcer and gastric carcinomas was 87.5% (70/80), 87.5% (84/96) and 93.3% (14/15) respectively. There was no significant relationship between cag A and vac A subtypes (P > 0.05). CONCLUSION: cag A(+) and vac A s1a/m2 subtype of Hp is predominant in patients with upper gastrointestinal diseases in Guangzhou, cag A(+) strains are further more common in patients with gastric cancer and peptic ulcer.

Adolescent↗

PubMed2000

[Protective effect of nitric oxide on pancreas and its relation to sulfhydryl compounds and oxygen free radicals].

OBJECTIVE: To investigate the effect of endogenous nitric oxide (NO) on acute necrosis pancreatitis in rats and its relation to sulfhydryl compounds and lipid peroxidation. METHODS: Acute necrosis pancreatitis in rats was induced by retrograde sodium taurocholate (5%) infusion into the pancreatobiliary duct (1 ml/kg body weight), and N(G)-nitro-L-arginine (L-NNA) was used as the inhibitor of endogenous NO. The effect of endogenous NO on pancreatic injury, serum amylase level, the pancreatic tissue levels of sulfhydryl compounds, and malonaldehyde (MDA, the end product of lipid peroxidation) was evaluated, respectively. RESULTS: Sodium taurocholate administration induced evident pancreatic tissue edema and acinar necrosis, and intrapancreatic hemorrhage occurred in 2/7 rats. Both serum amylase and tissue MDA [(1.25 +/- 0.28) nmol/mg x pr vs. (0.5 +/- 0.03) nmol/mg x pr, P < 0.05] were significantly increased, but tissue sulfhydryl compounds were decreased markedly. Pretreatment with the NO inhibitor, L-NNA (12.5 mg/kg body weight), significantly intensified acinar necrosis and increased the intrapancreatic hemorrhage (10/12). L-NNA also resulted in a further increase of serum amylase and tissue MDA [(3.0 +/- 0.40) vs. (1.25 +/- 0.28) nmol/mg x pr, P < 0.05], but it had no effect on the tissue sulfhydryl compounds. CONCLUSION: Endogenous NO has the effect of pancreatic protection, and its antioxidation may be responsible, at least in part, for the protective mechanisms. Sulfhydryl compounds may not be involved in NO's pancreatic protection mechanisms.

Amylases↗

PubMed2000

[A preliminary report of ocular surface disease treated by limbal transplantation].

OBJECTIVE: To evaluate the effect of ocular surface disease treated by limbal transplantation. METHODS: In a prospective study, 5l eyes of 50 patients were treated with three kinds of surgical techniques: first, conjunctival limbal autograft (CLAU) transplantation; second, corneal lamellar allograft combined with limbal autograft transplantation and third, corneal lamellar allograft combined with limbal allograft transplantation. Their effects were evaluated. RESULTS: All of the 18 patients of CLAU group were cured. The second surgical technique resulted in restoration of a stable ocular surface in 19 of 20 cases. 10 patients' visual acuities were improved two or more than two lines. 13 eyes of 12 patients were treated with the third surgical technique, resulting in graft ulceration in 4 patients and graft rejection in 4 patients with bad prognosis. CONCLUSIONS: The effect of unilateral ocular surface disease treated with limbal autograft transplantation is satisfactory. For bilateral ocular surface disease, the method of limbal allograft transplantation should be improved to resolve some problems such as graft rejection.

Adolescent↗