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Biomedical subjects

K Dohi

Publications and source records attributed to K Dohi.

At least 343 records · Page 19Linked to original sources

Mechanism of suppression of cloned human suppressor T cells.

We report the mechanism of suppression of suppressor T cell clone III-1-C5 using helper T cell clone III-1-B6, mitogen responses and rIL-2. Clone III-1-C5 suppressed the mixed lymphocyte reaction (MLR) by secreting alloantigen non-specific, MHC non-restricted suppressor factor(s). Clone III-1-C5 did not suppress mitogen (PHA, Con A, PWM) response nor proliferation by exogeneous rIL-2. Clone III-1-C5 suppressed proliferation by clone III-1-B6, which augments proliferation by direct cell to cell contact with responder cells and not by soluble factors. These results indicated that suppressor T cells exhibit suppressive effects not only by inhibiting IL-2 synthesis but by inhibiting the direct effects of helper T-cells.

Animals↗

Inhibition of IL-2 synthesis by donor-specific suppressor T cells in a renal transplant recipient.

A study was conducted to elucidate the mechanism of donor-specific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-specific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-specific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-specific suppressor T cells that produced a humoral non-specific suppressive factor only when stimulated by the donor PBL, and this factor suppressed MLR and CML by inhibiting IL-2 synthesis of the PBL.

Antibodies, Monoclonal↗

Doppler echocardiographic assessment of left ventricular diastolic function in patients with systemic lupus erythematosus.

Thirty patients with clinically inactive systemic lupus erythematosus (SLE) were examined by Doppler echocardiography to investigate the diastolic properties of the left ventricle. Twelve age-matched healthy women were also examined as controls. The pulsed wave transmitral Doppler flow velocity curves were digitized and curves of their first derivatives were obtained. Isovolumic relaxation time (IRT), acceleration and deceleration half-time of the rapid filling wave (E) and atrial contraction wave (A) (AHTe, DHTe, AHTa, DHTa), A/E, peak dE/dt, -peak dE/dt, peak dA/dt, -peak dA/dt were measured. In the SLE group, IRT and DHTe were prolonged, A, A/E, peak dA/dt and -peak dA/dt were increased compared with the control group. We conclude that patients with SLE have abnormal left ventricular diastolic function, even though their disease is clinically inactive.

Adult↗

Canine model of chronic pancreatitis due to chronic ischemia.

An experimental model of chronic pancreatitis was produced by a chronic ischemia which was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Macroscopic findings at 3 and 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin-cerulein test at 3 and 6 months, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. As this model closely resembles human chronic pancreatitis, we conclude that ischemia is an etiological factor in chronic pancreatitis.

Amylases↗

Enzymatic sulfation of glycosides and their corresponding aglycones by arylsulfate sulfotransferase from a human intestinal bacterium.

A novel type of arylsulfate sulfotransferase (ASST) from a predominant human intestinal bacterium catalyzes the stoichiometric transfer of a sulfate group from phenolic sulfate esters to phenols. We clarified that polyphenols were better substrates of this enzyme than the corresponding glycosides. Additionally, a coumarin derivative, esculetin, was sulfated by ASST at the 6-position to give 6-monosulfate. Therefore, ASST is more useful for the preparation of sulfated polyphenols at their specific hydroxyl groups and would play an important role in the metabolism of phenolic compounds in vegetable food and traditional medicines.

Arylsulfotransferase↗

Henoch-Schönlein purpura nephritis associated with polycythemia vera.

We present a 53-year-old man with rapidly progressive glomerulonephritis and Henoch-Schönlein purpura which developed during the course of treatment for polycythemia vera. An initial renal biopsy specimen showed mesangial proliferative glomerulonephritis. The patient was admitted to the hospital with cutaneous purpura and progressive renal failure after having received 700 mg of ranimustine over a 29 month period as therapy for the polycythemia vera. A second renal biopsy specimen revealed crescentic glomerulonephritis with deposition of immunofluorescent IgA. These data suggest that Henoch-Schönlein purpura nephritis may occur in response to ranimustine therapy.

Glomerulonephritis, Membranoproliferative↗

[A longitudinal study of brain atrophy and its relation with background factors and common carotid hemodynamics].

This longitudinal study was performed to clarify the relation between brain atrophy and common carotid hemodynamics. A total of 147 patients, including 70 males and 77 females, who had neither neurologic deficits nor organic lesions on computed tomography of the brain, were enrolled in this study. The ages of the patients ranged from 47 to 76 years (mean: 62 years) at the first diagnosis of brain atrophy. The patients were divided into three groups: 66 controls without hypertension or diabetes mellitus (Group I), 60 with hypertension (Group II) and 21 with both hypertension and diabetes mellitus (Group III). Brain atrophy was diagnosed by caudate head index (CHI). Mean blood flow volume (BF) at the right common carotid artery was measured by an ultrasonic quantitative flow measurement system. Both CHI and BF were measured twice at a mean interval 6.5 years. Increment in CHI per year (delta CHI) and decrement in mean blood flow volume per year (delta BF) were calculated. delta CHI of Group I and Group II had a significant relation with aging. delta CHI of Group III showed a larger increase than that of both Group I and Group II in subjects in the sixties. delta CHI had a significant relation with delta BF in each group. These results indicate that complication of both HT and DM, or decrement in mean blood flow volume may cause brain atrophy to progress.

Aged↗

[Compression of medulla oblongata by the dissecting aneurysm of the vertebral artery 7 years after its rupture: case report].

A 56-year-old female, who suffered a subarachnoid hemorrhage (SAH) due to spontaneous dissection of the right vertebral artery 7 years previously, was admitted to our hospital with headache and vertigo. She hadn't had any attacks of SAH for 7 years. A magnetic resonance imaging (MRI) showed a high signal intensity mass and a low signal intensity due to calcification on the right ventrolateral surface of the medulla on both T1 and T2 weighted images. Vertebral angiography showed complete occlusion of the cervical segment of the right vertebral artery (VA). Left vertebral angiography didn't reveal any retrograde filling of the intracranial segment of the right VA through VA union. Thus, the spontaneous entrapment by dissection of the vertebral artery was demonstrated 7 years after SAH with MRI and serial angiography.

Aortic Dissection↗

Telepathology is available for transplantation-pathology: experience in Japan using an integrated, low-cost, and high-quality system.

We examined the validity and accuracy of telepathology service in the histological diagnosis of biopsy specimens from human transplanted kidney and liver. The still video images of paraffin sections were transmitted via a two-way telephone by use of a digitized telephone network (Integrated Service Digital Networks, 64 kbits/sec). The images were displayed on monitors and diagnosed by an expert pathologist at Tottori University. The quality of transmitted still images was sufficient for the diagnosis, especially at higher magnifications. The average number of transmitted images was 6.2 in the kidney cases and 7.4 in the liver cases. The average time taken for examination of a case was 13 min (range 10 to 16 min). Of 12 biopsy specimens from transplanted kidneys, 10 were adequately diagnosed with the system. Sampling errors caused inadequate diagnosis in a case of cyclosporin tubulopathy, the still images of which were not transmitted. An expert pathologist rendered the diagnosis in a case showing mesangial sclerosis, which was later diagnosed as possible recurrent glomerulonephritis through direct microscopy. Biopsy specimens from 10 liver transplants were also tested using archival materials. Although the etiology of hepatitis could not be determined in one case, diagnoses by telepathology well agreed with the reported diagnoses made through direct microscopy. Telepathology may be an effective way to provide on-line consultations in transplantation pathology, especially for transplant teams lacking expert pathologists.

Adolescent↗

Angiotensin II receptor antagonist, TCV-116, prevents myocardial hypertrophy in spontaneously hypertensive rats.

Recently, it has been suggested that angiotensin II (AII) might be associated with cardiac hypertrophy and fibrosis. We investigated the preventive effect of an AII receptor antagonist, TCV-116, on the development of cardiac hypertrophy and fibrosis in spontaneously hypertensive rats (SHR) at 24 weeks of age through histopathological study and an AII receptor assay. Treatment with TCV-116, enalapril (an angiotensin-converting enzyme inhibitor, ACEI), and hydralazine for 20 weeks lowered systolic blood pressure (SBP) significantly (-39 mmHg, -45 mmHg, and -45 mmHg, respectively). The heart weight/body weight ratio, cardiac myocyte diameter, and percent cardiac fibrosis were significantly reduced by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The AII receptor density was significantly increased by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The results of this study suggest that AII receptors are involved in the development of cardiac hypertrophy and fibrosis in SHR. It was demonstrated that the AII receptor antagonist, TCV-116, was comparable to the ACEI, enalapril, in inhibiting the progression of cardiac hypertrophy and fibrosis via the AII receptor.

Angiotensin II↗

Distribution of thrombomodulin in patients with focal and segmental glomerulosclerosis (FSGS).

Thrombomodulin (TM), an endothelial cell surface glycoprotein, is a regulatory factor in the intravascular anticoagulant system. Furthermore, its plasma level is believed to reflect injury to the endothelial cell. In searching for changes in intraglomerular coagulation and endothelial cell injury during the clinical course of 14 patients with focal and segmental glomerulosclerosis (FSGS), we evaluated the distribution of thrombomodulin (TM) in the kidney by immunohistochemical methods. In the nephrotic stage, intraglomerular staining for TM was weak and segmental and occurred in 6 out of 9 patients (67%), but the incidence of TM expression was not different significantly from that in the normal kidney. Sclerotic lesion was negative for TM. In all patients with incomplete remission and with complete remission, strong and diffuse staining was seen in intra- and extraglomerular endothelial cells. Moreover, TM was scattered in sclerotic lesions. The present study suggest that the over-expression of TM in remission may be linked to recovery from endothelial cell damage and that TM may be closely involved in the repair of FSGS.

Adolescent↗

Effect of exercise on hemodynamics and urinary protein excretion in patients with early-stage diabetic nephropathy.

We investigated the effects of exercise on hemodynamics and urinary protein excretion in 15 patients with early-stage diabetic nephropathy (DN) as compared the findings with these of 16 healthy volunteers. Patients were divided into two groups according to their renal histopathologic findings; Group D0 consisted of 8 patients in whom light microscopy showed minor glomerular abnormalities and Group DI consisted of 7 patients with early stage diffuse lesions. The subjects exercised on a treadmill at a workload of 4.7 METS for 20 minutes. Systolic blood pressure, heart rate and the pressure rate product were significantly higher in the DI group than in the D0 and control groups during exercise. Diastolic blood pressure was similar among the three groups. Creatinine clearance was unchanged during exercise. Urinary albumin excretion, urinary acid soluble protein excretion and urinary alpha 1-microglobulin excretion were all significantly increased in group DI compared with the D0 and control groups. Excretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase activity were unchanged during exercise. Our findings suggest that this provocative exercise test is useful for diagnosing early-stage diabetic nephropathy.

Adult↗

Left ventricular diastolic function in patients on maintenance hemodialysis: comparison with hypertensive heart disease and hypertrophic cardiomyopathy.

To elucidate the differences in the left ventricular diastolic function between patients on maintenance hemodialysis with left ventricular hypertrophy and the those with left ventricular hypertrophy from other causes, 20 patients on maintenance hemodialysis (HD group; mean age 44 +/- 12 years), 12 patients with hypertensive heart disease (HHD group; mean age 43 +/- 10 years), and 10 patients with hypertrophic cardiomyopathy (HCM group; mean age 43 +/- 11 years) were examined non-invasively using diastolic time intervals and digitized echocardiograms. Ten age-matched healthy men (N group; mean age 43 +/- 12 years) were also examined. Compared with the HCM group, the HD and HHD groups had a decreased total left ventricular wall thickness and left atrial dimension, an increased ratio between the left ventricular enddiastolic dimension and total left ventricular wall thickness. The isovolumic relaxation and rapid relaxation periods were prolonged in the order of HCM, HHD, HD and N, but the active suction period was prolonged only in the HCM group. The peak rate of change in the left ventricular dimension during the rapid filling period was decreased in the HCM group, compared with the HD and the HHD groups. These results indicate that hemodialysis patients with left ventricular hypertrophy have some impairment in left ventricular diastolic function, but the degree of the disturbance is similar to that observed in those with hypertensive heart disease, but milder than that observed in those with hypertrophic cardiomyopathy.

Adult↗

[Intraglomerular distribution of thrombomodulin in patients with various renal diseases].

We investigated the intraglomerular distribution of thrombomodulin (TM) antigen in patients with various renal diseases. The subjects enrolled in this study were 28 patients with IgA nephropathy, 26 with collagen diseases, 10 with toxemia and 4 with DIC. Normal renal cortex used as a control was obtained from the normal pole of kidneys with a tumor of the opposite pole. Intraglomerular distribution of TM antigen was detected by an immunohistochemical method using a polyclonal antibody against human TM. The following results were obtained: 1) The staining intensity of TM on endothelial cells of glomerular tufts was higher in IgA nephropathy and collagen diseases than in the controls, but was the same in toxemia and DIC as in the controls. 2) The staining intensity of TM decreased with the progression of the glomerular lesion in IgA nephropathy and lupus nephritis. These findings suggest that the intraglomerular distribution of TM may be involved in the progression of glomerular lesions and in the acceleration of intraglomerular blood coagulation in various renal diseases.

Adolescent↗

[The clinico-pathological significance of hematuria in diabetics].

A clinico-pathological study was performed on 154 patients with diabetes mellitus to clarify the significance of glomerular hematuria. Glomerular hematuria was observed in 26 patients (16.9%), of whom 10 had complications of IgA glomerulonephritis and one had membranous nephropathy. The remaining patients (143 cases) were divided into two groups; a hematuria group (15 cases) and a non-hematuria group (128 cases). Patients in the hematuria group showed diabetic retinopathy, hypertension, massive proteinuria and the requirement for insulin therapy more often than those in the non-hematuria group (p < 0.01, p < 0.001, p < 0.001 and p < 0.01, respectively). In addition, the serum creatinine level in the hematuria group was significantly elevated compared to that in the non-hematuria group (p < 0.01). Histologically, patients in the hematuria group exhibited advanced diffuse lesions, nodular lesions, exudative lesions, microaneurysms, crescent formation, capsular adhesion and interstitial lesions more often than those in the non-hematuria group (all, p < 0.001). Furthermore, the vascular index in the hematuria group was significantly higher than that in the non-hematuria group (p < 0.001). It is suggested that glomerular hematuria in diabetic patients indicates the presence of diabetic nephropathy at an advanced stage or coexistence of primary glomerulonephritis.

Adolescent↗

Suppression of liver allograft rejection by administration of 15-deoxyspergualin. Comparison of administration via the hepatic artery, portal vein, or systemic circulation.

In this experiment, the effect of the administration route-the hepatic artery, portal vein, or systemic circulation-of the immunosuppressive drug 15-deoxyspergualin (DSG) on the suppression of liver allograft rejection is investigated. A 3-day injection of DSG at a dose of 0.32-1.28 mg/kg per day into the systemic circulation of a rat that had received a liver transplant was not effective in prolonging liver graft survival (14.3 +/- 2.9 days vs. 14.1 +/- 2.5 days for controls). However, the administration of DSG into the portal vein following liver transplantation markedly prolonged survival for up to 24.9 +/- 10.0 days. Survival times were prolonged even more when the DSG was administered via the hepatic artery for 3 successive days after liver grafting (30.9 +/- 9.6 days). The concentration of DSG in the blood following the one-shot injection of DSG was highest when DSG was administered via the hepatic artery, intermediate when injected into the portal vein, and lowest when injected into the systemic vein. In conclusion, DSG can inhibit liver graft rejection more effectively via the hepatic arterial route than via the portal vein or systemic circulation.

Animals↗