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Biomedical subjects

H Shiiki

Publications and source records attributed to H Shiiki.

At least 55 records · Page 3Linked to original sources
PubMed1996

Alterations in extracellular matrix components and integrins in patients with preeclamptic nephropathy.

The glomerular features of patients with preeclampsia consist of swelling of endothelial cells, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. These abnormalities are thought to resolve in the postpartum period. The distribution of extracellular matrix (ECM) components and integrins was investigated in 10 such patients. Frozen sections and paraffin-embedded sections were stained with antibodies to type IV collagen, laminin (LN), fibronectin (FN), vitronectin (VN), tenascin (TN), fibronectin receptor (FNR), and vitronectin receptor (VNR). In preeclamptic nephropathy, the accumulation of type IV collagen, LN, FN, TN, and FNR was observed in the thickened capillary walls, particularly in the subendothelial layer and, to some extent, in the mesangium. However, deposits of VN were sparse and the distribution of VNR was similar to that in normal kidney. In segmental sclerotic lesions, the amounts of type IV collagen, LN, FN, VN, and TN were increased, whereas those of FNR and VNR were markedly decreased. These results suggest that the materials deposited in the subendothelial space consist of ECM components as well as of plasma-derived proteins, and that the deposition of ECM components and of FNR may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions was linked to the accumulation of ECM components, but not to an interaction with integrins.

Adult↗
PubMed1996

Quantification of glomerular TGF-beta 1 mRNA in patients with diabetes mellitus.

Transforming growth factor-beta 1 (TGF-beta 1) is a primary determinant of the mesangial expansion observed in diabetic nephropathy. In this study, we quantitated the levels of intraglomerular TGF-beta 1 mRNA in patients with diabetes mellitus using a competitive polymerase chain reaction (PCR) method. Renal biopsy specimens were obtained from 29 patients with non-insulin-dependent diabetes mellitus. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. We also used this competitive PCR method to measure TGF-beta 1 cDNA by co-amplifying mutant templates of TGF-beta 1. We observed higher expression of TGF-beta 1 mRNA in glomeruli of patients with diabetic nephropathy as compared with normal glomeruli. Intraglomerular TGF-beta 1 mRNA was elevated, even in the early stage of diabetic nephropathy. Moreover, levels of intraglomerular TGF-beta 1 mRNA correlated with values of HbA1c. These data suggest that hyperglycemia induces intraglomerular TGF-beta 1 mRNA expression in vivo, and that TGF-beta 1 overproduction may be associated with the progression of diabetic nephropathy.

Aged↗
PubMed1996

[An autopsy case of systemic lupus erythematosus complicating leukocytosis, amegakaryocytic thrombocytopenia, interstitial pneumonitis, and pleulitis].

A 52-year-old female was admitted to our hospital in August 1988, for evaluation of purpura and gingival bleeding. Hematologic examination showed mild leukocytosis (12,400/microliter) and severe thrombocytopenia (1,000/microliter). On bone marrow examination, megakaryocyte count was normal and the number of myeloblasts was increased (7.2%). Serological examination was positive for anti-nuclear antibody and anti-DNA antibody. She was diagnosed as having idiopathic or autoimmune thrombocytopenia, and received thrombocyte transfusion and gamma-globulin administration. Hematologic values improved temporarily, but leukocytosis and thrombocytopenia recurred. On the 22nd hospital day, leukocytes increased to 49,300/microliter and thrombocytes decreased to 10,000/microliter. Bone marrow myeloblasts were also increased to 18.8%, and she was suspected of having myelodysplastic syndrome. Then, hematologic values improved simultaneously, and she was discharged in November 1988. After the discharge, leukocyte count ranged from 6,000 to 16,500/microliter, but the number of bone marrow myeloblasts was normal. However, transient thrombocytopenia appeared in association with decrease or absence of bone marrow megakaryocytes and rise of platelet associated-IgG, (PA-IgG) to 99.6 ng/10(7) cells. From September to December 1989, she complained of fever, morning stiffness, multiple arthralgia, and oral ulcer. On serological findings, she was positive for LE cell. Therefore, she was diagnosed as having systemic lupus erythematosus (SLE). In January 1990, she had a high grade fever and dyspnea. Bilateral pleuritis and interstitial pneumonitis were shown on the chest roentgenogram. She received gamma-globulin administration, methylprednisolone pulse therapy, and mechanical ventilation. However, hypoxia developed rapidly, and she died of respiratory failure. Autopsy revealed severe interstitial pneumonitis, fibrinous pleuritis, fibrinous pericarditis, and vasculitis in the arcuate artery of the kidney. This is the first report of SLE complicating thrombocytopenia associated with decrease of megakaryocytes and rise of the PA-IgG, and severe leukocytosis associated with increased bone marrow myeloblasts.

Fatal Outcome↗
PubMed1996

[Clinicopathological study of diabetic nephropathy in the elderly].

We studied the relationship between clinical characteristics and renal structural changes in 29 elderly patients in whom non-insulin-dependent diabetes mellitus was diagnosed when they were 60 years of age or older. The clinical stage of nephropathy was graded according to the criteria of the Ministry of Health and Welfare of Japan: stage 1 (12 patients), normoalbuminuria; stage 2 (11 patients), microalbuminuria; stage 3 (1 patient), persistent proteinuria; stage 4 (5 patients), chronic renal failure. Renal biopsy specimens were semiquantitatively evaluated with regard to diffuse glomerular lesions, nodular lesions, and vascular lesions. In patients at stage 1, minimal-to-moderate diffuse lesions were observed, and vascular lesions were already present. In patients at stage 2, various alterations in diffuse lesions were observed and were associated with prominent changes in the vascular lesions. More advanced changes in the diffuse and vascular lesions were noted in patients at stages 3 and 4, but nodular lesions were found in only one patient. These patients had a high incidence of hypertension and ischemic heart disease. We conclude that elderly diabetic patients with nephropathy of different clinical stages have different underlying diabetic renal lesions.

Aged↗
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

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↗
PubMed1995

[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↗
PubMed1995

Localization of macrophage migration inhibitory factor (MIF) to secretory granules within the corticotrophic and thyrotrophic cells of the pituitary gland.

BACKGROUND: Macrophage migration inhibitory factor (MIF) was one of the first lymphokine activities to be discovered and was described almost 30 years ago to be a soluble factor(s) produced by activated T lymphocytes. In more recent studies, MIF has been "rediscovered" to be an abundant, pre-formed constituent of the anterior pituitary gland and the macrophage, and to be a critical component in the host response to septic shock. Pituitary-derived MIF enters the circulation after infectious or stressful stimuli and appears to act to counterregulate glucocorticoid suppression of cytokine production. MATERIALS AND METHODS: Immunoelectron microscopy utilizing a combination of anti-MIF and anti-pituitary hormone-specific antibodies was used to study the ultrastructural localization of MIF within the anterior pituitary gland. Pituitaries were obtained from resting, unstimulated mice and from mice 16 hr after endotoxin administration. The release of MIF also was investigated in vitro by examining the effect of corticotropin-releasing hormone (CRH_ on the AtT-20, corticotrophic cell line. RESULTS: MIF localizes to granules present exclusively in ACTH and TSH secreting cells. Within each cell type, a subset of granules was found to contain both MIF and ACTH, or MIF and TSH. The pituitary content of MIF-containing granules decreased significantly after experimentally induced endotoxemia. In seven pituitaries examined 16 hr after LPS injection, the number of MIF-positive granules diminished by 38% in corticotrophic cells and by 48% in thyrotrophic cells when compared with controls (p < 0.05). CRH was observed to be a potent MIF secretagogue in vitro, inducing the release of MIF from corticotrophic cells at concentrations lower than that required for ACTH release. CONCLUSION: These data provide ultrastructural information that identify MIF to be a novel anterior pituitary hormone, support earlier studies showing a time-dependent release of pituitary MIF during endotoxemia, and suggest an important, systemic role for MIF in the stress response to infection and other stimuli.

Adrenocorticotropic Hormone↗
PubMed1994

Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis.

Both PDGF and IL-1 play important roles as autocrine growth factors for cultured mesangial cells, and may be closely associated with the progression of glomerulonephritis. In this study we investigated intraglomerular expressions of PDGF-B and IL-1 alpha mRNA in mice with bovine serum albumin (BSA) nephritis, a model of immune complex-mediated glomerulonephritis, using the reverse transcription-polymerase chain reaction (RT-PCR) method. We also quantified intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation between the level of intraglomerular PDGF-B mRNA expression and the degree of observed glomerular injury. While expression of neither PDGF-B nor IL-1 alpha mRNA was detected in glomeruli from control mice, both were strongly expressed in glomeruli from mice with BSA nephritis. IL-1 alpha mRNA in glomeruli showed low accumulation in mice with mild glomerular injury, and was increased in mice with moderate glomerular injury. In contrast, high intraglomerular expression of PDGF-B mRNA occurred in all mice with mild glomerular injury and continued throughout the course of the disease. We observed no correlation between the level of PDGF-B mRNA expression and the histologic grade of renal damage. These results suggest that PDGF and IL-1 have different growth properties, and PDGF might play a role as a competence factor rather than a progression factor in the pathogenesis of immune complex-mediated glomerulonephritis.

Animals↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1994

[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↗
PubMed1993

Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus.

Advanced glycosylation end products (AGEs) accumulate on long-lived extracellular matrix proteins and have been implicated in the micro- and macrovascular complications of diabetes mellitus. Within the arterial wall, AGE-modified proteins increase vascular permeability, inactivate nitric oxide activity, and induce the release of growth-promoting cytokines. Recently developed anti-AGE antibodies were used in an immunohistochemical analysis of coronary arteries obtained from type II diabetic and nondiabetic patients. High levels of AGE reactivity were observed within the atherosclerotic plaque present in vessels from selected patients with diabetes. Considered together with the pathological effects of AGEs on vascular wall homeostasis, these data support the role of advanced glycosylation in the rapidly progressive atherosclerosis associated with diabetes mellitus.

Aged↗
PubMed1993

Urinary levels of IL-6 in patients with active lupus nephritis.

Using the IL-6 dependent hybridoma, MH60.BSF2, we measured urinary levels of interleukin 6 (IL-6) in 29 patients with active lupus nephritis. We detected IL-6 activity in the urine of 24 (83%) of 29 patients before the initiation of therapy. The median value of urinary IL-6 levels in patients with a histologic diagnosis of WHO class IV on renal biopsy was significantly higher than that in patients with other classes (p < 0.01). After treatment, urinary levels of IL-6 decreased significantly (p < 0.001). These data suggest that urinary levels of IL-6 may be a valuable tool for monitoring the progression of lupus nephritis.

Biomarkers↗
PubMed1992

Glomerular tuft ballooning in mitomycin-C-induced renal impairment.

Severe ballooning of the glomerular tufts was observed in a 65-year-old man who was treated with mitomycin C (MMC) and had typical MMC-induced renal lesions. He developed renal failure and severe anaemia 6 months after initiation of chemotherapy. Ballooned tufts were caused by enormous expansion of the sub-endothelial space simultaneously associated with mesangiolysis. Glomerular cysts, described in a variety of disorders including thrombotic microangiopathy and diabetes mellitus, are derived from cystically dilated and united capillary luminae secondary to mesangiolysis. The morphogenesis of this unusual lesion when induced by MMC differs from that of the glomerular cysts previously reported.

Aged↗