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Biomedical subjects

K Dohi

Publications and source records attributed to K Dohi.

At least 289 records · Page 16Linked to original sources
PubMed1996

Role of tissue inhibitors of metalloproteinase in diabetic nephropathy.

We evaluated the role of tissue inhibitors of metalloproteinase-1 (TIMP-1) in patients with diabetic nephropathy by comparing the serum and urine TIMP-1 levels with those of renal biopsy specimens. A total of 35 diabetic patients were divided into four groups, D0, DI, DII and DIII-IV, according to the severity of diffuse glomerular lesions using Gellman's criteria. Using serum and 24-hour urine specimens, TIMP-1 was measured by a sandwich enzyme immunoassay. Serum and urinary TIMP-1 showed significant increases in association with the progress of glomerular diffuse lesions. There was no correlation between serum TIMP-1 and serum creatinine, creatinine clearance, serum and urinary beta 2-microglobulin, urinary NAG, HbA1c, or urinary TIMP-1. There was a significant correlation between urinary TIMP-1 and urinary albumin, and was a significant correlation between urinary TIMP-1 and urinary NAG. We conclude that TIMP-1 has a potential role in the regulation of glomerular matrix accumulation in diabetic nephropathy.

Adult↗
PubMed1996

Hypergammaglobulinaemic purpura of Waldenström and Ro/SSA autoantibodies.

Seven out of nine patients (78%), seen over a 13-year period with hypergammaglobulinaemic purpura of Waldenström were found to have antibodies to Ro/SSA. Over this period we saw 175 patients who had antibodies to Ro/SSA. In six of the seven patients, associated diseases were recognized. Five had Sjögren's syndrome, and one had systemic lupus erythematosus with Sjögren's syndrome and thyroiditis (and died 19 years after initial presentation from cerebral infarction). Screening for antibodies to Ro/SSA is important in the diagnosis of patients with hypergamma-globulinaemic purpura, and is helpful in predicting prognosis.

Adult↗
PubMed1996

[Serum and urinary pyridinium cross-links in patients with predialysis chronic renal failure].

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p < 0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

Adult↗
PubMed1996

HLA-DR8 subtyping by polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis: a simple and practical genotyping method.

Two hundred Japanese panels were serologically typed for human leukocyte antigen (HLA) - DR to assign 65 HLA-DR8 haplotypes, which were then subdivided into two genotypes, i.e., DRB1*0802 and DRB1*0803, by a polymerase chain reaction (PCR)--based, simple, and practical method. The panels possessing DR8 specificity were firstly subjected to PCR with a couple of primers specifically to amplify their DR52 associated group--DRB1 genes. PCR products were then denatured in the presence of formamide, electrophoresed in a non-denaturing polyacrylamide gel, and visualized by silver staining. The same DRB1 products of these samples were also mixed with the DRB1*1302, and simultaneously analyzed by the same procedure. Electrophoretic mobilities of the samples were compared with those of the typing standards to genotype their DR8--DRB1 alleles by using the characteristic polymorphism in the single-stranded DNAs and the heteroduplexes. This method, designated PCR--DNA conformation polymorphism (DCP) analysis, allowed for genotyping of the DR8-DRB1 alleles without using sequence-specific oligonucleotide probes (SSOP) or restriction endonucleases. The entire process after PCR was completed within a few hours. The tested panels were also genotyped for DRB1 gene by the PCR-SSOP method for comparison with results obtained by the PCR-DCP method. Satisfactory coincidence was achieved and it represented how accurately the new system genotyped DRB1*0802 and DRB1*0803. PCR-DCP analysis was thus shown to be practical and useful for subtyping of serologically defined DR8 specificities.

Base Sequence↗
PubMed1996

Effect of donor fasting on survival of pancreas and heart grafts after warm ischemia.

Livers from fasted animals are believed to be more vulnerable to ischemic injury than those from fed donors. However, we have recently shown the opposite: livers from fasted rats were more tolerant to ischemic injury. Indeed, the survival rate of 60 min warm ischemic damaged livers increased from 0 to 90% if donor rats were fasted for three days. In this study, we examined how donor fasting affects the outcome of pancreas and heart preservation. BN rats were used as both donors and recipients, and recipients of pancreatic grafts were rendered diabetic prior to transplantation. Pancreatic or heart grafts were subjected to 90 min or 25 min of warm ischemia and were transplanted into the right side of the necks of recipients rats. The viability rate of hearts transplanted from fed donors into fed recipients was only about 11% (1/9) after transplantation. However, the viability rate with fasted donors was 75% (6/8). The rate of successful pancreatic grafting from fed donors into fed recipients was 28.6% (2/7), and that from fasted donors to fed recipients was 41.7% (5/12). These results confirm that the nutritional status of the donor is an important factor in the outcome of not only liver, but also pancreas and heart preservation during transplantation, although the effect of fasting on pancreatic graft is marginal.

Animals↗
PubMed1996

Clinical and morphological predictors of renal outcome in adult patients with focal and segmental glomerulosclerosis (FSGS).

In this retrospective study, we examined 35 adult patients with biopsy-proven, primary focal and segmental glomerulosclerosis (FSGS) and nephrotic syndrome to determine whether any of the clinical and morphological features of FSGS were associated with a higher risk of a poor renal outcome. Clinical factors assessed were the age, sex, amount of urinary protein, and presence of microscopic hematuria, hypertension and renal dysfunction at onset in each patient. Morphological parameters included the number of segmental sclerosis and global sclerosis, sclerosis score, location of segmental sclerosis, mean glomerular diameter, grade of tubulo-interstitial changes, and presence of vascular lesions. Twenty-three patients (66%) were in complete or incomplete (partial) remission, and 12 (34%) were non-responders at the end of follow-up. On univariate analysis, the age at onset, sclerosis score, mean glomerular diameter, and grade of tubulo-interstitial changes in no response were significantly greater than those parameters in remission. Multivariate logistic regression analysis revealed that the degree of tubulo-interstitial changes and mean glomerular diameter were independent risk factors for a poor renal outcome. These findings suggest that the estimation of these latter two parameters allows the nephrologist to predict the probable course and prognosis of an adult with FSGS. Intensive and prolonged therapy is recommended for patients without these two morphological features.

Adult↗
PubMed1996

[Identical twin sisters with IgA nephropathy].

This report described 45-year-old identical twin sisters with IgA nephropathy. Case 1 presented with microscopic hematuria and proteinuria at the age of 39. Case 2 was found proteinuria at the age of 32. Both the physical examination and laboratory data of these cases were normal. Serum level of IgA was not elevated. The renal biopsy specimen of two cases showed slight mesangial proliferation by light microscopy and mesangial IgA deposition by immunofluorescence microscopy. Their serotype for HLA was found to be HLA-A2, A24, Bw35, Cw1, Cw3, DRw8, DRw12. Several reports indicated the familial occurrence of patients with IgA nephropathy and a strong association with HLA-Bw35 in those patients. The present cases also suggested that an abnormal immune response-linked HLA system may be involved in the development of IgA nephropathy.

Diseases in Twins↗
PubMed1995

rap1 p21 regulates the interaction of ras p21 with RGL, a new effector protein of ras p21.

We have recently found that ralGDS family members (RGL and ralGDS) are putative effector proteins of ras p21. rap1 p21 is a small GTP-binding protein which has the same amino acid sequence as the effector loop of ras p21. We examined the effect of rap1 p21 on the interaction of ras p21 with RGL. The GTP-bound form of rap1 p21 interacted with RGL as well as did ras p21. rap1 p21 inhibited the interaction of ras p21 with RGL. RGL was phosphorylated by cyclic AMP-dependent protein kinase (protein kinase A). Phosphorylation of RGL did not affect its binding to ras p21 and rap1 p21 under the conditions that phosphorylation of Raf-1 reduced its affinity for ras p21. These results demonstrate that rap1 p21 but not protein kinase A regulates the interaction of ras p21 with RGL and suggest that rap1 p21 and protein kinase A may cooperate to distinguish the signal or ras p21 to RGL from that to Raf-1.

Cloning, Molecular↗
PubMed1995

Simultaneous evaluation of nitric oxide synthesis and tissue oxygenation in rat liver allograft rejection using near-infrared spectroscopy.

Near-infrared (NIR) spectroscopy was applied to rat liver allografts for assessing nitric oxide (NO) synthesis and tissue oxygenation as a means of monitoring the rejection response following liver transplantation. Orthotopic liver transplantation was performed in rats, which were assigned to three groups as follows: group 1, a syngeneic combination (lewis to Lewis); group 2, an allogeneic combination (ACI to Lewis); and group 3, an allogeneic combination treated with 15-deoxyspergualin. NIR spectroscopy was performed on the grafts in recipients, and the relative changes in nitrosyl-Hb (NO bound to erythrocyte hemoglobin), oxy-Hb, and oxidized cytochrome oxidase (Cyt.aa3) were obtained. The level of nitrosyl-Hb was significantly elevated from postoperative day (POD) 3 in group 2 compared with that in group 1, which remained constant (P < 0.05). In group 3, the elevation was significantly suppressed. These data indicate that the alloimmune response is associated with a dramatic change in NO synthesis in grafted livers. In a separate experiment, NO synthesis was also increased after long cold preservation (24 hr) in syngeneic liver transplants. However, the increase was transient and subsided on POD 3. Levels of oxy-Hb and oxidized Cyt.aa3 in group 2 were significantly decreased when parenchymal disorder was confirmed histologically (POD 6 and 8), compared with those in group 1, which remained constant (P < 0.05). In group 3, both of these levels showed improvement. Thus, our NIR spectroscopy technique was shown to be capable of assessing simultaneously both the immune response and the degree of immune-induced destruction of allograft tissue following liver transplantation through monitoring of NO synthesis and tissue oxygenation.

Animals↗
PubMed1995

The usefulness of severe combined immunodeficiency (SCID) mice to study human carcinogenesis.

In the present study, we engrafted normal colonic epithelial and histologically diagnosed colonic adenomas from a familial adenomatous polyposis (FAP) patient into severe combined immunodeficient (SCID) mice and subsequently examined them histologically and molecular biologically. Successful engraftment and metastasis was observed. The facts that human normal colonic epithelium and adenomatous polyps can take in SCID mice indicates the possibility that this human SCID mouse system will be useful for investigating the dynamics of human carcinogenesis in various tissues.

Adenomatous Polyposis Coli↗
PubMed1995

A tailgut cyst found accompanying rectal cancer: report of a case.

Tailgut cysts are rare congenital lesions. To date, only four cases have been reported in Japan, and the occurrence of a tailgut cyst with rectal cancer has never been documented. We describe here the case of a patient in whom a tailgut cyst in the retrorectal space was associated with rectal cancer. Preoperative computed tomography scans and endorectal ultrasonography failed to identify the lesion as cystic, instead suggesting an involved lymph node. This case emphasizes the necessity for careful diagnosis of masses in the retrorectal space in patients with rectal cancer.

Adenocarcinoma, Mucinous↗
PubMed1995

Human herpesvirus-6 infection in renal allografts: retrospective immunohistochemical study in Japanese recipients.

This study was conducted to determine the incidence and clinical significance of human herpesvirus-6 (HHV-6) infection in renal allografts. A total of 105 biopsy specimens from 72 recipients were immunohistochemically examined for the presence of HHV-6 antigen, which localized in the distal tubular epithelial cells and in a few lymphocytes infiltrating into the interstitium. HHV-6 antigen in the tubular epithelia was detected in 63 (61.2%) specimens. Categorically, a higher incidence of the antigen was noted in specimens of accelerated rejection (3/4, 75.0%), acute rejection (28/3, 73.7%), and cyclosporin nephropathy (8/11, 72.7%). The antigen was present and absent an almost equal number of times in the categories of chronic rejection, intraoperative and routine protocol biopsies. Repeated biopsies were performed in six cases showing HHV-6 antigen, only one of which underwent transplant nephrectomy due to severe chronic rejection. Single or multinucleated giant cells in distal tubuli occurred in 10 (9.5%) specimens in a scattered manner. All of them were diagnosed as acute or chronic rejection. The giant cells showed no immunoreactivity for HHV-6, cytomegalovirus, or herpes simplex virus. These results indicate overall that HHV-6 infection is common in renal allografts and might be reactivated in acute rejection or cyclosporin nephropathy. The presence of HHV-6 antigen, however, does not necessarily correlate with a poor prognosis for the renal graft nor with the occurrence of giant cells in distal tubuli.

Adult↗
PubMed1995

Immunohistochemical detection of advanced glycosylation end products within the vascular lesions and glomeruli in diabetic nephropathy.

Numerous studies over the years have implicated advanced glycosylation end products (AGEs) in the pathogenesis of many of the complications of diabetes and normal aging. The recent development of specific antibodies against AGE-modified proteins has facilitated investigations on the formation and tissue distribution of AGEs. We used anti-AGE antibodies to localize AGEs within kidney specimens obtained from both diabetic and nondiabetic individuals. Immunohistochemical staining using anti-AGE antibody showed a high level of AGE accumulation in diabetic and aged vascular intima, particularly along the inner elastic layer of arteries. Positive staining also was observed within nodular and severe diffuse lesions of glomeruli as well as in hyaline deposits of arterioles. These data support a pathogenic role for advanced glycosylation in the renal complications of diabetes and aging.

Adult↗