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Biomedical subjects

K Dohi

Publications and source records attributed to K Dohi.

At least 307 records · Page 17Linked to original sources

Monitoring for engraftment following rat orthotopic liver transplantation by in vitro amplification of Y-chromosome gene using polymerase chain reaction.

The polymerase chain reaction (PCR) using primers specific for the rat Y-chromosome gene made it possible to distinguish a very small number of male rat cells from a large excess of female rat cells. In nonimmunosuppressed LEW recipients of ACI liver allografts, the donor cells in the bloodstream disappeared rapidly by day 3, earlier than the biochemical changes indicative of liver dysfunction. In immunosuppressed LEW recipients of ACI liver allografts, the donor cells were detected for a longer time. Moreover, in LEW recipients surviving for long period, the PCR revealed mixed-microchimerism. Our results indicated that this Y chromosomal gene-specific PCR method is useful for assessing engraftment following rat liver transplantation.

Animals↗

Development of a rat model for orthotopic liver transplantation for hepatocellular carcinoma.

BACKGROUND: Surgical resection is of limited benefit in hepatocellular carcinoma accompanied by severe liver cirrhosis or multicentric hepatic cancer. The long-term survival of patients with advanced hepatocellular carcinoma after transplantation is quite poor. We have studied the characteristics, natural course, and cause of diethylnitrosamine-induced liver cancer in rats and have shown it to be a good model of liver cancer in human beings. Therefore we performed orthotopic liver transplantation (OLT) in rats with diethylnitrosamine-induced liver cancer to study the patterns of recurrence. METHODS: Diethylnitrosamine 100 parts per million in drinking water was administered daily for 4 months to male inbred LEW rats. A laparotomy was performed 120 or 134 days after commencing the oral diethylnitrosamine to confirm the induction of cancer confined grossly to the liver. The livers were resected, and orthotopic transplantation with livers of normal LEW rats was performed. RESULTS: By day 150 all the rats in the non-OLT group died of intraabdominal hemorrhage caused by spontaneous rupture of liver cancer (mean survival time +/- SD, 138.2 +/- 5.3 days; n = 14). However, the OLT (day 120) group recovered their body weight comparatively early after transplantation and survived a maximum of 218 days until death from recurrence (203.8 +/- 21.3 days; n = 4). A significant extension in survival time was observed (p < 0.01). In autopsies performed at the time of death, metastatic liver cancer was observed in the transplanted livers with two showing metastases to the lung. The cause of death was cancer in all the rats. However, the OLT (day 134) group all died of major complications of severe pneumonia and disseminated intravascular coagulation within 2 weeks of OLT (141.3 +/- 5.0 days; n = 4). CONCLUSIONS: After liver transplantation to rats with hepatocellular cancer confined to the liver, recurrence was observed at a comparatively early stage in all transplant recipients. Although a significant prolongation of survival was noted, they all died of cancer. The timing of transplantation is also an important factor. This experimental liver transplantation model of progressive rat liver cancer will be useful in the study of primary liver cancer in human beings.

Animals↗

Dose-response of a radiation induction of a germline mutation at a hypervariable mouse minisatellite locus.

Dose-response of an induction of a germline mutation was studied at a hypervariable mouse minisatellite locus, Ms6hm, which consists of tandem repeats of a sequence motif GGGCA. Male C3H/HeN mice were exposed to various doses of 60Co gamma-ray and mated with unirradiated C57BL/6N female mice. Matings were done at various time after irradiation to assess the effects of radiation on spermatozoa, spermatids and spermatogonia. DNA samples of F1 offsprings were analysed by Southern blotting for the repeat length mutation at the Ms6hm locus. The mutation frequency per gamete of the paternal allele was 9.1% for the unirradiated control group. The spermatids stage was most sensitive to radiation and a statistically significant dose-response was observed. The mutation frequency of the paternal allele in F1 mice increased to 22% for 1 Gy, 28% for 2 Gy, and 28% for 3 Gy. The spermatogonia stage was less sensitive to radiation, and the mutation frequencies of the paternal allele were 14% for 2 Gy, and 16% for 3 Gy. The spermatozoa stage germ cells were also less sensitive and the frequency of mutation of the paternal allele increased to 14% for 3 Gy. However, these increases were statistically not significant. Possible mechanisms of radiation induction of germline mutation at the hypervariable minisatellite locus will be discussed.

Alleles↗

Significance of the HLA-DQB matching in one-haplotype identical kidney transplant pairs and the matching analysis by the polymerase chain reaction (PCR)--heteroduplex--polymorphism method.

Sixty-five living related kidney transplant pairs were analyzed for matching at HLA class II loci by the polymerase chain reaction (PCR)--sequence specific oligonucleotide probe (SSOP) method. The retrospective HLA matching study revealed that there were many early graft loss cases despite the DQB compatibility, contrary to our expectation. There were 54 DRB1 one-mismatched cases, in which 7 of the 11 (64%) DQB zero-mismatched cases had lost their grafts, while the graft loss cases were only 10 of the 43 (23%) DQB one-mismatched pairs (P value = 0.0006). The DQB matching of these cases was studied in detail, because the PCR-SSOP methods are based on the detection of sequence polymorphisms in a relatively narrow range, i.e., recognized sequences by SSOPs. The PCR--heteroduplex--polymorphism analysis method was developed to analyze the polymorphism in exon 2 of the DQB1 gene. However, all the pairs proved to be compatible for the DQB, demonstrating that the DQB compatibility was associated with a harmful influence on the graft outcome. These observations suggested that the DQB1 incompatibility might exert the low responsiveness to HLA haplo-identical allogeneic transplants.

Base Sequence↗

Acute left ventricular failure with pulmonary edema following pericardiocentesis for cardiac tamponade--a case report.

We describe the complications of pericardiocentesis and their management in an 18 year-old man. This patient was admitted because of dyspnea and was found on echocardiogram to have cardiac tamponade with coexisting left ventricular dysfunction. He developed acute left ventricular failure with severe pulmonary edema immediately after pericardiocentesis. This complication may have been caused by an abrupt increase in venous return to the failing left ventricle following the release of the pericardial compression. Therefore, pericardial fluid must be drained with caution in pericardiocentesis, especially in cardiac tamponade patients with left ventricular dysfunction, and hemodynamics should be monitored both during and after this procedure.

Acute Disease↗

A unique case of renovascular hypertension caused by combined renal artery disease.

We present a unique case of renovascular hypertension due to combined renal artery disease in a 22-year-old woman. Renal angiography revealed renal artery stenosis with poststenotic dilatation and an aneurysm due to fibromuscular dysplasia in the left kidney, and a congenital arteriovenous fistula in the right kidney. The results of a captopril test and plasma renin sampling demonstrated that the renin-angiotensin-aldosterone system was stimulated in both kidneys, accounting for the hypertension in this patient. Almost all cases of renovascular hypertension are due to only one underlying renal artery disease. This is the first case of renovascular hypertension associated not only with renal artery stenosis and an aneurysm due to fibromuscular dysplasia, but also with a congenital arteriovenous fistula.

Adult↗

[A case of polyarteritis nodosa presenting with multiple intrarenal aneurysms and accelerated hypertension].

A twenty-one-year-old male was admitted to our hospital because of hypertension and proteinuria. He had felt general fatigue and low grade fever for one month. Blood pressure was 180/120 mmHg on admission. Laboratory findings showed 3+ proteinuria and 1+ occult blood in urinalysis; an accelerated erythrocyte sedimentation rate (ESR) of 39 mm/hr; elevation of LDH to 755 IU/l. Antinuclear antibody was positive with a titer of 1: 160, with a speckled pattern. Plasma renin activity and serum aldosterone were markedly elevated to 25.8 ng/ml/hr and 585.3 pg/ml, respectively. Renal function had declined mildly; endogenous creatinine clearance was 60 ml/min. Renal arteriogram demonstrated multiple intrarenal aneurysms in the bilateral kidneys. Aneurysms, 5-8 mm in diameter were located in the arteries from the interlobar to interlobular region. He was diagnosed as having polyarteritis nodosa (PN) and was then treated with 20 mg/day of prednisolone and monthly pulse therapy of cyclophosphamide. After steroid, cyclophosphamide and anti-hypertensive therapy, he became well and had normal blood pressure. The patient was considered a rare case of PN with multiple intrarenal aneurysms and accelerated hypertension. We discuss aneurysms in PN and accelerated or malignant hypertension documented in the literature.

Adult↗

[Immunohistochemical study of the endomyocardial biopsy of systemic lupus erythematosus].

The mechanisms of cardiac involvement in systemic lupus erythematosus (SLE) were studied using immunohistochemical staining of endomyocardial biopsy specimens from 14 patients with SLE and normal coronary arteriograms. All 14 specimens showed mild interstitial edema, 11 showed mild cardiac fibrosis, and another two cases showed moderate cardiac fibrosis with myocardial derangements. Four specimens showed moderate cell infiltration in the interstitium. Area of fibrosis, diameter of myocardium and area of interstitial edema were increased in the SLE patients compared to the control cases. Immunofluorescence showed IgG and fibrinogen deposition in the membrane of cardiac myocytes and in the interstitium. Immunohistochemistry found no B lymphocytes in any of the seven SLE cases. T lymphocytes were observed in all seven SLE cases, and OKT 8 lymphocytes were increased significantly in the interstitial tissue as compared with OKT 4 lymphocytes. At endomyocardial biopsy, all 14 patients were receiving corticosteroid therapy and had low activity disease. The results suggest that cardiac tissue damage was associated with immunological abnormalities and might progress silently under conditions in which the disease activity was suppressed by corticosteroid therapy.

Adult↗

Diagnostic significance of urinary fibronectin in diabetic nephropathy.

We evaluated the diagnostic utility of urinary fibronectin (FN) in patients with diabetic nephropathy by comparing the findings with those of renal biopsy specimens. A total of 46 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 24-hour urine specimens, FN was measured by a solid phase enzyme-linked immunosorbent assay. The urinary excretion of FN was significantly higher in the overt proteinuric group than in the normo- and micro-albuminuric groups. Urinary FN level showed a significant increase with respect to the progress of glomerular diffuse lesions. There was a weak correlation between the urinary level of FN and serum creatinine level and a weak inverse correlation between the urinary level of FN and creatinine clearance. When patients with overt proteinuria were excluded from the analysis, there was no correlation between the urinary level of FN and serum creatinine level, creatinine clearance, or that of beta 2-microglobulin and NAG. The findings indicate that urinary FN may be useful in estimating pathologic conditions, especially the early stage of diabetic nephropathy.

Adult↗

[Endothelial dysfunction of the infarct-related coronary artery after reperfusion therapy].

The response of the infarct-related coronary artery to acetylcholine (20, 30, 50 micrograms) was investigated in 30 patients without restenosis during a 4-month follow-up period after direct percutaneous transluminal coronary angioplasty (PTCA) of the left proximal anterior descending coronary artery. The patients were divided into two groups according to wall motion as obtained by the centerline method from a left ventricular angiogram: moderate group (n = 10) with reduced wall motion with less than 20 abnormal contraction segments (moderate reduction at the infarcted site), severe group (n = 20) with reduced wall motion with 20 or more abnormal contraction segments (severe reduction). The acetylcholine-induced percentage changes in luminal diameter were assessed at the PTCA site and the distal portion of the coronary artery and the effect of acetylcholine was compared at the two sites. Coronary artery diameter in the moderate and severe groups displayed 8.1 +/- 24.9% and 7.4 +/- 30.8% contraction at the PTCA site and 38.3 +/- 46.3% and 72.5 +/- 28.2% contraction at the distal portion, respectively. Severe group had greater contraction at the distal portion than at the PTCA site. Vasoconstriction of the patent infarct-related coronary artery tended to occur in the infarcted area where wall motion was severely affected. In addition, endothelial dysfunction appears to be induced by a lengthy interruption of epicardial coronary blood flow and is present in the patent infarcted coronary artery without restenosis.

Acetylcholine↗

[Renal involvement in Sjögren's syndrome--interstitial nephritis and glomerulonephritis].

Renal involvement is well recognized extraglandular manifestation of primary Sjögren's syndrome (SS). The most common histopathological lesion is an interstitial lymphocytic infiltrate with tubular atrophy and fibrosis. The clinical presentation may be hyposthenuria, overt or latent distal renal tubular acidosis and less commonly Fanconi's syndrome. These tubular dysfunctions correlate with the presence of interstitial lymphocytes. Immunoregulatory alterations consisting of impaired T-cell function and B-cell hyperactivity probably play a pathogenetic role in the development of interstitial nephritis in SS. Glomerulonephritis in SS has been described in a limited number of case reports. Variant modes of pathogenesis have been proposed in these cases where glomerulonephritis has been associated with immune complex deposition and cryoglobulinemia.

Glomerulonephritis↗

Diagnostic significance of urinary transferrin in diabetic nephropathy.

We evaluated the diagnostic utility of urinary transferrin (Tf) in patients with diabetic nephropathy by comparing the diagnostic findings with those of clinical stage and renal biopsy specimens. According to the rate of urinary albumin excretion, a total of 60 patients with non-insulin-dependent diabetes mellitus were separated into normoalbuminuria (< 28.8 mg/day), microalbuminuria (28.8 approximately 288 mg/day), and overt proteinuria (> 288 mg/day). They were also divided into 5 groups, D0, DI, DII, DIII and DIV according to the severity of glomerular diffuse lesions using Gellman's criteria. Thirty-eight non-diabetic volunteers were used as controls. Using 24-hour urine specimens, Tf was measured by latex-immuno-turbidimetry. Urinary concentrations of albumin, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) were also evaluated. Urinary Tf was significantly increased in the diabetic patients relative to the non-diabetic controls. The incidence of microtransferrinuria (440 approximately 4,400 micrograms/day) was 33.3% in normoalbuminuria, 63.2% in microalbuminuria, and 18.2% in overt proteinuria. The incidence of overt transferrinuria (> 4,400 micrograms/day) was 0%, 36.8% and 81.8%, respectively. Among the diabetic patients, urinary Tf showed a significant increase with respect to the progress of glomerular diffuse lesions. The glomerular diffuse lesions of 10 normoalbuminuric cases with microtransferrinuria were graded as DI in 8 cases, DII in 1 case, and DIII in 1 case. There was a significant correlation between the urinary excretion of Tf and that of albumin, alpha 1-microglobulin or NAG. The findings indicate that urinary Tf may be useful in detecting diabetic nephropathy at an early stage.

Adult↗