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M Kusaka

Publications and source records attributed to M Kusaka.

At least 19 recordsLinked to original sources
PubMed2001

Autoantibodies detectable in the sera of silicosis patients. The relationship between the anti-topoisomerase I antibody response and HLA-DQB1*0402 allele in Japanese silicosis patients.

Eighty-one Japanese silicosis patients and 66 healthy volunteers were analyzed for autoantibodies by ELISA, and HLA-genotyping using the PCR-RFLP method was performed. Anti-topoisomerase I (anti-topo I) autoantibodies were detected in seven patients without any clinical features of autoimmune diseases such as progressive systemic sclerosis (PSS), although anti-topo I have been mostly reported in PSS patients. Antibodies directed to RNP, ssDNA, dsDNA and cent-B were not detected among the anti-topo I positive patients. The indirect immunofluorescent staining pattern of Hep-2 cells with the sera of anti-topo I positive silicosis patients demonstrated the typical mode of anti-topo I autoantibodies observed in the patients with PSS. The allelic frequency of HLA-DQB1*0402 was significantly higher in anti-topo I positive patients (28.6%) than in anti-topo I negative patients (1.5%, P < 0.001) or healthy controls (0.8%, P<0.001). HLA-DQB1*0301, DQB1*0601 and DPB1*1801 alleles were more frequently detected in anti-topo I positive patients than in the patients without anti-topo I or in healthy volunteers, but no significant difference was observed. DQB1 allele is associated with the induction of anti-topo I autoantibodies in Japanese silicosis patients, but the allele is not the same as in Caucasian PSS patients. Another allele (DQB1*0402) plays an important role in Japanese silicosis patients. The most important factor to induce anti-topo I autoantibodies seems not to be the type of alleles themselves, but the position of some specific amino acid residues in the DQ beta first domain. These findings will be useful for preventing occupational autoimmune diseases.

Aged↗
PubMed2001

Metastases to the penis from carcinoma of the prostate.

A 58-year-old man presented with dysuria at the Osaka Medical College Hospital in November 1996. Laboratory examination revealed elevated serum prostate-specific antigen (PSA) to > 100 ng/mL. Adenocarcinoma of the prostate with metastasis to the bone was diagnosed after a biopsy of the prostate and bone scintigraphy; hormonal therapy was administered. Although bone metastasis was well controlled and the serum PSA level declined to within normal levels (2.0 ng/mL), several painless nodules were found on the penile glans. Biopsy of the nodules showed that the penile tumor was a metastasis from the prostate cancer. The patient underwent partial penectomy for relief from penile pain. The serum PSA level showed no elevation 3 months after the partial penectomy, suggesting that careful observation of prostate cancer patients is necessary, even when oseous metastasis is well controlled and serum PSA levels are kept within normal ranges by hormonal therapy. The case also indicates that urologists should consider the possibility of metastasis to the penis from prostate cancer.

Adenocarcinoma↗
PubMed2001

Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domain.

Autoantibodies against DNA topoisomerase I (anti-topo I) have been reported to be specific to systemic sclerosis (SSc), however, anti-topo I was detected in patients with silicone breast implants, SLE without features of SSc, and rheumatic diseases. We detected anti-topo I positive silicosis patients without any symptoms of autoimmune diseases. The correlation between anti-topo I autoantibody responses and HLA class II has been established. HLA-DRB1*1502; DQB1*0601 has been reported to be the most frequent anti-topo I associated haplotype among Japanese SSc patients. In this study, haplotype HLA-DR15; DQ6 was detected in all 4 anti-topo I positive Asian Japanese SSc patients randomly selected. Furthermore, HLA-DQB1*0402 was identified in 3 of 4 anti-topo I positive silicosis patients. These findings coincide with the results of a previous study, in which all 4 Japanese patients with anti-topo I had the DQB1*04 alleles, whereas no studies among Caucasian-Americans, African-Americans and Choctaw Indians found the involvement of DQB1*04. We investigated common features among various DQB 1 alleles. HLA-DQB I with a distinct characteristic is clearly involved in the anti-topo I response irrespective of ethnic groups, the main disease, or silica exposure. A common positioning of distinct amino acids, (i.e. positions 14, 30, 57 and 77 of the DQbeta1 domain are methionine, tyrosine, aspartic acid and threonine, respectively,) seems to be associated with anti-topo I response. The above-mentioned amino acid sequence is detected in alleles *0301, *0303, *0306, *0401, *0402, *0601 and *0602.

Alleles↗
PubMed2000

Activation of the heart by donor brain death accelerates acute rejection after transplantation.

BACKGROUND: Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation. METHODS AND RESULTS: Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fisher, F344) were rejected significantly earlier (mean+/-SD, 9. 3+/-0.6 days) by their (Lewis) recipients than hearts from living donor controls (11.6+/-0.7 days, P=0.03). The inflammatory response of such organs was accelerated, with rapid expression of cytokines, chemokines, and adhesion molecules and brisk infiltration of associated leukocyte populations. Upregulation of major histocompatibility class II antigens increased organ immunogenicity. Acute rejection evolved in hearts from brain-dead donors more intensely and at a significantly faster rate than in controls. CONCLUSIONS: Donor brain death is deleterious to transplanted hearts. The resultant upregulation of inflammatory factors provokes host immune mechanisms and accelerates the acute rejection process in unmodified hosts.

Animals↗
PubMed2000

Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients.

Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities such as the appearance of autoantibodies and complications of autoimmune diseases. Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, has been considered to play a role in the pathogenesis of autoimmune diseases. It has been found that serum soluble Fas (sFas) levels are elevated in silicosis patients (SIL) and the sFas message is dominantly expressed in peripheral blood mononuclear cells (PBMC) derived from these individuals. In the present study, one tried to detect alternatively spliced variant messages including typical sFas message and found four that were highly and frequently expressed, and which possess a signal peptide domain, but not transmembrane and signal transducing domains, in PBMC derived from SIL. Functional mutations were not detected in Fas and FasL genes in silicosis PBMC. Still, alternative spliced variants of the Fas gene including typical sFas message appear to play an important role in the immunological dysregulation in SIL.

Aged↗
PubMed2000

Activation of inflammatory mediators in rat renal isografts by donor brain death.

BACKGROUND: Brain death (BD) has been thought to influence the early course of transplanted organs by triggering a series of nonspecific inflammatory events that in turn may increase the kinetics and intensity of the immunological host responses. In this study early nonspecific, cellular, and molecular changes occurring in kidney isografts from BD donors are compared with those from normal anesthetized, ventilated controls. METHODS: After induction of brain death, the animals were mechanically ventilated for 6 hr before organ removal. Only rats with stable blood pressure (mean arterial pressure >80 mmHg) were included. Serum creatinines were measured daily. Representative grafts were harvested 6 hr after brain death and between 1 hr and 5 days after engraftment for morphology, immunohistology, and reverse transcriptase-polymerase chain reaction. The presence of serum cytokines was assessed by enzyme linked immunoabsorbant assay. RESULTS: Serum creatinine levels rose slightly in recipients from BD donors. Serum interleukin-1beta levels increased within 6 hr versus controls (P<0.05). mRNA levels of interleukin-1beta and macrophage inhibitory protein-1 in the kidneys were up-regulated transiently before engraftment (6 hr after BD) and 1 hr after revascularization (P<0.05). By immunohistology, numbers of infiltrating polymorphonuclear leukocytes peaked at 24 hr in parallel with intragraft induction of P- and E-selectin, complement, and other proinflammatory chemokines and cytokines. At 5 days, the isografts from BD donors were highly infiltrated by host leukocyte populations associated with intense up-regulation of their products. In contrast, those from control donors remained relatively normal through this initial follow-up period. CONCLUSIONS: The intense nonimmune inflammation produced in isografts after donor BD may represent the initial stages of a continuum between an initial nonspecific and later immune reactivity, when placed in the context of allotransplantation.

Animals↗
PubMed2000

A model of gradual onset brain death for transplant-associated studies in rats.

BACKGROUND: The relatively few studies that have examined the systemic events after brain death have primarily involved large animals. For more precise definition of the physiology of this central catastrophe and its influence on peripheral organs, we have established a reproduceable model of gradual onset brain death in rats. METHODS: The central injury is induced by graded inflation of a Fogarty catheter placed intracranially under EEG and blood pressure monitoring. The rats were mechanically ventilated for 6 hr before removal of their kidneys. Complications and mortality are discussed. RESULTS: The majority (83%) of the 100 experimental animals could be used as organ donors. After a transient period of autonomic storm, the mean arterial blood pressure remained consistently between 80-100 mmHg, not appreciably different from controls. Despite normotension, the transplanted kidneys from brain dead donors showed a significantly longer interval to regain uniform cortical color and turgor than kidneys from control animals. CONCLUSIONS: We describe a controlled model of gradual onset brain death in the rat in which normotension can be sustained for several hours before the kidneys are removed for transplantation. Despite stable donor blood pressure, ischemia of peripheral organs may explain in part the increased incidence of delayed graft function of cadaver kidneys compared with those from living donors. This model is suitable for transplant-related studies involving organs from donors with irreversible central injury.

Animals↗
PubMed2000

Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage.

Animals↗
PubMed2000

Effect of probucol in a murine model of slowly progressive polycystic kidney disease.

Epithelial proliferation, extracellular matrix remodeling, and interstitial inflammation are central elements in the pathogenesis of slowly progressive polycystic kidney disorders. Probucol, an antioxidant that lowers plasma cholesterol, has been shown to decrease smooth muscle cell proliferation and macrophage accumulation in blood vessels and to prevent restenosis after coronary angioplasty. We determined in 30-day-old male BDF1-pcy hybrid mice (derived from mating DBA/2FG-pcy and C57BL/6FG-pcy) the effect of probucol administered in the diet (1%) for 200 days on kidney weight relative to body weight (KW/BW), cyst expansion, renal interstitial fibrosis, and serum urea nitrogen (SUN) concentration. Animals were fed a moderately high-protein diet (HPD, 36%) to accentuate the development of renal cysts and to promote interstitial fibrosis. Probucol decreased serum cholesterol from 68 to 16 mg/dL but had no effect on food intake or body weight. Probucol decreased relative kidney size from 4.16% +/- 0.55% to 2.64% +/- 0.12% KW/BW (P < 0.01), SUN from 30.5 +/- 1.8 to 25.9 +/- 1.0 mg/dL (P < 0.05), cystic index from 2.45 +/- 0.11 to 1.36 +/- 0.10 (P < 0.01), and fibrosis index from 2.40 +/- 0.11 to 1.82 +/- 0.08 (P < 0.01). We conclude that probucol ameliorates the progressive deterioration in renal function and structure in pcy mice ingesting a relatively high level of dietary protein.

Animals↗
PubMed2000

Over-expression of the decoy receptor 3 (DcR3) gene in peripheral blood mononuclear cells (PBMC) derived from silicosis patients.

Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, is considered to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Recently, a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds FasL and inhibits FasL-induced apoptosis, has been identified. Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities. We have found that serum soluble Fas (sFas) levels are elevated in silicosis patients and that sFas message is dominantly expressed in PBMC derived from these patients. This study examined DcR3 gene expression in PBMC derived from patients with silicosis, SLE, or progressive systemic sclerosis (PSS), and compared it with that in healthy volunteers (HV). The relative expression level of the DcR3 gene was examined in PBMC derived from 37 patients with silicosis without clinical symptoms of autoimmune disease, nine patients with SLE, 12 patients with PSS, and 28 HV using the semiquantitative multiplex-reverse transcriptase-polymerase chain reaction (MP-RT-PCR). The correlation between the relative expression level of the DcR3 gene and multiple clinical parameters for respiratory disorders and immunological abnormalities in individuals with silicosis was analysed. The DcR3 gene was significantly over-expressed in cases of silicosis or SLE when compared with HV. In addition, the DcR3 relative expression level was positively correlated with the serum sFas level in silicosis patients. It is unclear, however, whether over-expression of the DcR3 gene in silicosis is caused by chronic silica exposure, merely accompanies the alteration in Fas-related molecules, or precedes the clinical onset of autoimmune abnormalities. It will be necessary to study these patients further, establish an in vitro model of human T cells exposed recurrently to silica compounds, and resolve whether the increase in DcR3 mRNA expression is a cause or consequence of disease.

Adult↗
PubMed2000

Renal allograft protection with losartan in Fisher-->Lewis rats: hemodynamics, macrophages, and cytokines.

BACKGROUND: We sought to assess the effects of angiotensin receptor blockade on glomerular hypertension, macrophage recruitment, and cytokine expression, all of which contribute to the development of chronic graft injury in this model. METHODS: The effects of treatment with the specific angiotensin II type 1 (AT1) receptor antagonist, losartan, were assessed over 24 weeks in F344-->LEW rats (LOS, N = 9) versus vehicle-treated F344-->LEW controls (CON, N = 9). RESULTS: UprotV rose progressively in CON (from 7.0 +/- 2.9 to 41 +/- 17 mg/day at 24 wk) but remained at baseline in LOS (4.2 +/- 0.6 to 9.4 +/- 1.3 mg/day, P < 0.05 vs. CON). Glomerular capillary pressure (PGC) was increased in CON (71 +/- 1 mm Hg at week 20), but remained within the normal range in LOS rats (54 +/- 2 mm Hg, P < 0.05). Glomerulosclerosis averaged 0.3 +/- 0.2% in LOS versus 4 +/- 2% in CON rats (P < 0.05). Tubulointerstitial injury was minimal in both LOS and CON rats (+). The overexpression of renal cortical cytokine mRNA levels for the monocyte chemoattractants, monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as interleukin-1, inducible nitric oxide synthase, and transforming growth factor-beta, assessed by competitive reverse transcription-polymerase chain reaction, was suppressed in LOS versus CON rats at 20 weeks. Macrophage and T-cell numbers were decreased, and MCP-1, RANTES, and intercellular adhesion molecule-1 staining in the graft, identified by immunohistochemistry, were attenuated in LOS versus CON rats. CONCLUSIONS: The renoprotective effects of losartan in F344-->LEW rats were associated with lowered PGC, inhibition of macrophage chemoattractants and recruitment, and suppression of macrophage-associated cytokines at 20 weeks. These findings suggest that chronic allograft injury in F344-->LEW rats is, to a large extent, mediated by angiotensin II-dependent mechanisms and that these involve glomerular hemodynamics, macrophages, and macrophage-associated cytokines.

Angiotensin Receptor Antagonists↗
PubMed2000

Volumetric determination of progression in autosomal dominant polycystic kidney disease by computed tomography.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal enlargement and renal failure. We evaluated sequential radiocontrast-enhanced computed tomography (CT) scans to determine the rate of kidney enlargement in patients with ADPKD. METHODS: Ten adult patients with ADPKD (4 men and 6 women) with initial serum creatinine levels </=1.6 mg/dL had at least two sequential CT scans more than three years apart. The mean patient age at the initial CT study was 33.8 years, and the mean initial serum creatinine concentration was 1.1 mg/dL (range 0.6 to 1.6 mg/dL; range of calculated creatinine clearances 60 to 135 mL/min/1. 73 m2). Total volume (Vt) was determined by manual tracing of renal areas in contiguous 5 to 10 mm thick axial CT slices for each kidney. The area of noncystic parenchyma (Vp) in each slice was determined by differential densitometry segmentation analysis of contrast-enhanced tissue, and total cyst volume (Vc) was the difference between Vt and Vp. The mean diameters of individual cysts were measured sequentially in selected cases. RESULTS: The mean initial Vt, Vp, and Vc values (+/- SEM) were 561 +/- 66, 243 +/- 19, and 317 +/- 57 mL per kidney, respectively. In 10 patients, after a mean of 5.7 years (range 3.3 to 11.9), Vt increased 323 +/- 79 mL (P < 0.01, range -25 to 1182 mL); the rate of volume increase was 53.9 +/- 10.4 mL/year/kidney (P < 0.001). In eight patients with repeat contrast-enhanced scans, Vt, Vp, and Vc increased 211 +/- 58 mL (P < 0.005), 26 +/- 11 mL (P > 0.05), and 185 +/- 52 mL (P < 0.01), respectively. In 19 individual spherical cysts selected in six patients, the mean initial volume was 15.0 +/- 7.2 mL (range 1.1 to 137 mL), and the average rate of volume increase was 0.52 +/- 0.21 mL/month (P < 0.025, range 0.02 to 4.15 mL/month). In five patients who eventually required dialysis, 11.2 years after the initial CT scan, the initial cyst/kidney volume ratio (combined for both kidneys) exceeded 0.43; four patients with lower cyst/kidney volume ratios had serum creatinine levels <1.5 mg/dL, 8.7 years after the initial CT scan. CONCLUSIONS: On the basis of this preliminary survey of archival material, we conclude that conventional contrast-enhanced CT scans can be used to quantitate volume components of progression in ADPKD. The rates of individual kidney and cyst enlargement are highly variable within and between patients, but overall, the values increase over time. The volume fraction of kidneys comprised of cysts may be a useful indicator of ADPKD progression.

Adult↗
PubMed2000

Accelerated rejection of renal allografts from brain-dead donors.

OBJECTIVE: To define the potential influences of donor brain death on organs used for transplantation. SUMMARY BACKGROUND DATA: Donor brain death causes prompt upregulation of inflammatory mediators on peripheral organs. It is hypothesized that this antigen-independent insult may influence the rate and intensity of host alloresponsiveness after engraftment. METHODS: The rates of survival of unmodified Lew recipients sustained by kidney allografts from brain-dead, normal anesthetized, and anesthetized ventilated F344 donors were compared. Brain death was induced by gradually increasing intracranial pressure under electroencephalographic control. Tracheotomized brain-dead animals and anesthetized controls were mechanically ventilated for 6 hours before transplant nephrectomy. The rate and intensity of the acute rejection event were examined by histology, immunohistology, and reverse transcriptase-polymerase chain reaction. RESULTS: Animals bearing kidneys from brain-dead donors died of renal failure secondary to acute rejection at a significantly faster rate than those from anesthetized living controls or anesthetized animals ventilated for 6 hours. Within 3 hours after placement and reperfusion of brain-dead donor grafts, significant neutrophil infiltration was observed, followed by increasing numbers of macrophages and T cells. mRNA of proinflammatory mediators detected in kidneys within 6 hours of brain death and upregulated even before transplantation increased thereafter and appeared to accelerate and amplify host alloresponsiveness, as manifested by the rapid expression of chemokines, cytokines, adhesion molecules, and major histocompatibility complex class II antigens in the engrafted organ. The process evolved in the controls less intensely and at a slower rate. CONCLUSIONS: Donor brain death is a significant risk factor for peripheral organs used for transplantation. The activated state of such organs appears to trigger host immune mechanisms that accelerate the process of acute rejection. The effects of this central injury may explain in part the less satisfactory performance of cadaver organs in human transplantation compared with those from living sources.

Animals↗
PubMed2000

Effect of a novel immunosuppressant, FTY720, on allograft survival after renal transplant in rats.

FTY720 was developed by chemical modification of ISP-1 which was purified from culture filtrates of an ascomycete, Isaria sinclairii. We evaluated the effect of FTY720 on allograft survival using a rat renal transplantation model in which Wistar King Aptekman Hokkaido rats (WKAH, RT1(K)) served as the organ donor and Lewis rats (LEW, RT1(l)) as the recipient. WKAH renal allografts were acutely rejected by the untreated LEW recipients at a mean graft survival +/- SD of 7.2 +/- 0.4 days (n = 5). Consecutive oral administration of FTY720 following transplantation significantly prolonged allograft survival in a dose-dependent manner over the range of 0. 05-3 mg/kg/day. The mean allograft survival of the recipients treated with FTY720 at a doses of 0.05, 0.1, 0.5, 1, and 3 mg/kg/day was 12.2 +/- 3.3 (n = 5, p < 0.05, vs. untreated host), 11.2 +/- 2.4 (n = 5, p < 0.05, vs. untreated host), 13.6 +/- 0.9 (n = 5, p < 0.01, vs. untreated host), 14.6 +/- 1.7 (n = 5, p < 0.01, vs. untreated host) and 20.2 +/- 0.8 days (n = 5, p < 0.01, vs. untreated host). In the recipients treated with FTY720 (3 mg/kg/day), the number of peripheral blood lymphocytes significantly decreased. From the results of the flow cytometric study, FTY720 significantly diminished the percentage of interleukin-2 receptor (IL-2R)-positive cells in the allografts (6.34 +/- 0.81% in the untreated recipients vs. 3.10 +/- 0.86% in the recipients treated with FTY720, p < 0.05). As to the CD4/CD8 ratio of splenic cells and graft infiltrate, there was no significant difference between the untreated hosts and the recipients treated with FTY720. In conclusion, FTY720 significantly extended rat renal allograft survival and the immunosuppressive effects of FTY720 may be due to a reduction in not only the number of peripheral lymphocytes but also the percentage of IL-2R-positive cells in the allografts.

Animals↗
PubMed1999

Exploitation of the continuum between early ischemia/reperfusion injury and host alloresponsiveness: indefinite kidney allograft survival by treatment with a soluble P-selectin ligand and low-dose cyclosporine in combination.

BACKGROUND: We have shown previously that sPSGL, a soluble glycoprotein ligand for P and E selectins, reduces the events associated with ischemia/reperfusion injury of the kidney. In the present study, we have attempted to modulate differentially early inflammatory influences and later host alloresponsiveness in an LBNF1-Lewis renal graft model by treatment with sPSGL in combination with a marginally effective dose of cyclosporine (CsA). METHODS: Four experimental groups were studied: group 1=control animals receiving vehicle only; group 2=sPSGL monotherapy alone; group 3=low-dose CsA; group 4=sPSGL plus low-dose CsA. Grafts were removed at 1, 3, 5, and 7 days (n=3/time point) and assessed by histology, immunohistology, and reverse transcriptase-polymerase chain reaction. Long-surviving grafts in recipients of groups 3 and 4 were followed functionally for more than 28 weeks. RESULTS: Graft function was prolonged indefinitely in recipients in group 4, all of which survived for more than 200 days. In contrast, survival of animals in groups 1 and 2 was not increased substantially, whereas only 4 of 17 animals in group 3 (23.5%) survived more than 24 days (P<0.01). Five days after engraftment, necrosis was relatively minimal in group 4 organs but pronounced in those of the other groups. By immunohistology, numbers of infiltrating CD4+ and CD8+ T cells and ED1+ macrophages were significantly diminished in group 4 allografts compared with those of the other groups. Serial assessment of chemokine and cytokine mRNA expression confirmed these findings. The long-term effects of CsA treatment alone were compared with those of sPSGL in combination with CsA. Proteinuria remained virtually absent in group 4 recipients. Morphologically, the few long-surviving grafts in group 3 showed signs of chronic rejection; those in group 4 remained relatively normal. CONCLUSIONS: Although treatment with sPSGL alone showed no apparent influence on the acutely rejecting transplants, at least by the parameters examined in this study, it produced indefinite survival of kidney grafts when used in combination with low-dose CsA. The data support the influence of early nonspecific injury on later immunological rejection.

Animals↗
PubMed1999

Closely linked polymorphic markers for determining the autosomal dominant allele (Cy) in rat polycystic kidney disease.

The Han:SPRD strain is an SD-background strain known to be a model of polycystic kidney disease (PKD) expressed through an autosomal dominant gene (Cy). However, different genotypes of this strain cannot be identified in the neonatal period. First, to establish an accurate method of determining the genotypes (Cy/Cy, Cy/+, +/+) which cause different disease progressions, we used polymorphic markers on rat chromosome 5. PCR products of tissue DNA templated with D5Rat9 showed distinct patterns on electrophoresis indicating three genotypes. Second, to determine whether the same locus plays a major role in expressing PKD, we performed linkage analyses in a [BN x (BN x Han:SPRD)F1] backcross. Cy/Cy and Cy/+ also caused PKD in a BN background. In this backcross, we discovered that D5Rat11 is located closer to the Cy locus than D5Mgh10, which is regarded as one of the closest loci. We conclude that D5Rat9 and D5Rat11 are useful markers for determining the presence of the Cy allele, which is regarded as the gene responsible for PKD.

Alleles↗