Detection of serum IL-6 in patients with diabetic nephropathy.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
H Koide
Publications and source records attributed to H Koide.
Improvement of cerebral blood flow and cognitive function following pacemaker implantation in patients with bradycardia.
We investigated the effects of pacemaker implantation on cerebral blood flow and cognitive function in 14 severely bradycardic patients (mean age 75.2 years). Cerebral blood flow and verbal intelligence improved after the pacemaker implantation. Systolic and mean arterial blood pressure was significantly reduced after the implantation. Changes in cerebral blood flow significantly correlated with changes in heart rate in polynomial regression analysis, but not with changes in cardiac output. Before the implantation, verbal cognitive function was lower in bradycardic patients than in age-matched control subjects, and brain CT showed significant advanced atrophy in these patients. However, verbal cognitive function was also improved after the implantation. Pacemaker implantation in the severe bradycardic elderly should be beneficial not only for cardiac function but also for brain function. We concluded that these results suggest that heart rate is one of the important factors in the regulation of cerebral circulation in patients with severe bradycardia. Pacemaker implantation in the elderly improved quality of life and may prevent mental deterioration.
Aged↗
Effects of low-protein diet on mRNA for ECM components, MMPs and TIMPs in glomeruli of focal glomerular sclerosis.
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Animals↗
[Prospective study on the influence of social activity on development of dementia in the neurologically normal elderly].
We investigated the rate of development of dementia in 84 neurologically normal elderly subjects living in an old-age home (30 subjects, mean 77.2 years) or their own home 954, 73.7) prospectively. We examined cerebral blood flow (CBF), Hasegawa's scale (HS) and Kohs' block design test 6 to 9 years before this study (1991). HS and Kohs' IQ were significantly lower in the old-age home group than that in their own home group at that time. However, there were no demented subjects. Mortality was 21%, and we confirmed 9 dementia and 6 stroke cases during the period of observation. Twenty-seven percent of the old-age home group showed dementia in 1991. This rate was significantly higher than that for the elderly living in their own home (6.7%). Occurrence of stroke was also significantly higher in the former group than in the latter group. The subjects who developed stroke during observation showed a high incidence of dementia. Mean CBF measured on the first examination was significantly lower in dementia cases with stroke than in dementia cases without it. We performed MRI in 4 demented cases in 1991 (Fig. 1). Two cases showed no significant lesions and the other cases showed cerebral infarction which could cause dementia. These results indicate that life style and social environment may have significant effect on aging of the brain and on development of dementia in the elderly.
Aged↗
[Glomerulonephritis and cytokines].
In the past year, major advances have been made in understanding the role of cytokines in the pathogenesis and progression of chronic glomerulonephritis. This paper reviews recent data on the pivotal roles of cytokines including interleukins-1 and -6, tumor necrosis factor, platelet-derived growth factor, transforming growth factor-beta, fibroblast growth factor and insulin-like growth factor in mediating glomerular cell proliferation and in leading to glomerulosclerosis.
Animals↗
[Significance of periventricular hyper-intensity in T2 weighted MRI on memory dysfunction and depression after stroke].
We studied the effect of periventricular hyperintensity (PVH) in T2 weighted MRI on memory function and post-stroke depression in 159 patients with cerebrovascular diseases. Memory function was assessed with Hasegawa's scale, and depressive state was estimated with Zung's self-rating depression scale. Patients showing diffusely distributed PVH had significantly low scores in memory function tests. Localized PVH around the anterior horns of the laterals ventricle was also associated with impaired memory function when the area of PVH was large. The incidence of post-stroke depression was high in patients with large PVH around the anterior horn in comparison with patients with PVH around the posterior horn. The severity of PVH around the posterior horn did not affect memory function and post-stroke depression. These findings suggest that memory dysfunction and post-stroke depression were accelerated by the diffusely or anteriorly distributed PVH.
Aged↗
Two adult cases of IgM-associated mesangial proliferative glomerulonephritis.
Two adult patients with mesangial proliferative glomerulonephritis with diffuse IgM deposition in the glomeruli are reported. Case 1 was a 25-year-old female with nephrotic syndrome who showed complete remission after treatment with prednisolone (PSL). Case 2 was a 46-year-old male with asymptomatic proteinuria who showed incomplete remission (0.5-1.0 g/24 hr) of urinary protein without any medication. In light microscopy, these patients revealed minimal or slight proliferation of glomerular mesangial cells without glomerular sclerosis and crescent formation. Deposition of IgM and C3 was observed in the glomerular mesangial areas and capillary walls by immunofluorescence. Electron-dense deposits were observed in the glomerular mesangial areas in these patients. Mesangial proliferative glomerulonephritis associated with diffuse IgM deposition in the glomeruli appears to have a benign clinical course. It has also been suggested that this disease has variant clinical courses since we recently experienced two other patients with mesangial proliferative glomerulonephritis with focal IgM deposits who showed renal tubular dysfunction or chronic renal failure.
Adult↗
Intranephron distribution of creatine content in rats.
Creatine is a high energy phosphate donor and play an important role not only in muscle contraction, but also in buffering intracellular energy storage. In this study, we have identified the creatine content in microdissected nephron segments with an ultramicromethod. All nephron segments tested contained creatine, however the distribution was not uniform. Glomerulus, cortical thick ascending limb of Henle's loop and distal tubule possessed comparatively large amounts of creatine when calculated as pM/micrograms tissue protein. When calculation was made as pM/mm tubule length, the first segment of the proximal tubule and the distal tubule were the highest. These results suggest the existence of heterogeneity in creatine content along the nephron as one of the biochemical characteristics in individual nephron segments.
Analysis of Variance↗
Mutations that abolish the ability of Ha-Ras to associate with Raf-1.
Recent studies have revealed that Ras can associate physically with Raf. In the present study, we tested 34 mutants of Ha-Ras carrying substitution(s) in the region of residues 23-71 for their ability to associate with Raf-1. Mouse Ba/F3 cell lysates were incubated with each mutant Ras protein, in either the guanosine 5'-[gamma-thio]triphosphate (GTP gamma S)- or the guanosine 5'-[beta-thio]diphosphate (GDP beta S)-bound form, and the anti-Ras antibody Y13-238. The immunoprecipitates were analysed for the presence of Raf-1 by Western blotting with an anti-Raf-1 antibody. Six mutants of Ras, E31K, P34G, T35S, D38N, D57A and A59T, failed to bind Raf-1. Mutations N26G, V29A, S39A, Y40W, R41A, V44A, V45E, L56A and T58A partially reduced the ability to bind Raf-1. All the other mutants could associate with Raf-1 with nearly the same efficiency as that of wild-type Ras. Thus, the Raf-I-binding ability of Ras appears to be affected by mutations in the N-terminal region, and in particular, by those in and neighboring the effector region (residues 32-40) and in the region (residues 56-59) flanking the N-terminal of Switch II. The abilities to bind Raf-1 and to induce neurite outgrowth of pheochromocytoma (PC) 12 cells correlate to each other for 22 Ras mutants. However, mutation A59T, which does not reduce the neurite-inducing or transforming activities, abolishes the ability to bind Raf-1. In contrast, mutations Y32F, K42A and L53A, which impair the neurite-inducing activity of Ras, have no effect on the Ras.Raf-1 association. Partially reduced Raf-1-binding ability was observed for mutants V29A, S39A, Y40W, R41A, V44A, L56A and T58A, which exhibit full neurite-inducing activity, and also for mutant V45E, which has no activity of neurite induction.
Animals↗
A case of thin basement membrane syndrome associated with idiopathic membranous nephropathy.
A 59-year-old woman has had persistent microscopic hematuria for 10 years. A few days after the onset of upper respiratory tract infection, edema and severe proteinuria appeared. In renal biopsy, an electron micrograph revealed electron dense deposits in the subepithelial regions with diffuse thinning of the glomerular basement membrane. These glomerular findings were compatible with thin basement membrane syndrome associated with membranous nephropathy. On the basis of our review of the literature, the association of these two diseases seems to be very rare.
Basement Membrane↗
Effects of enalapril on endothelin-1 and growth factor gene expression in diabetic rat glomeruli.
We have previously reported that the mRNA levels of endothelin (ET-1), tumor necrosis factor-alpha), (TNF-alpha), platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF-beta), and basic fibroblast growth factor (bFGF) all increased with age in diabetic rat glomeruli. We have now assessed the effect of the angiotensin-converting enzyme inhibitor enalapril on the expression of the ET-1, TNF-alpha, PDGF-B, TGF-beta, and bFGF genes in 24-week-old rat glomeruli after streptozotocin injection. Animals were divided into controls, enalapril-treated diabetic rats, and untreated diabetic rats. Treatment continued for 24 weeks. Enalapril reduced both creatinine clearance (p < 0.001) and urinary protein excretion (p < 0.01) in diabetic rats. Enalapril produced a nonsignificant 15 mm Hg reduction in blood pressure in diabetic rats. Enalapril also attenuated the increases in ET-1 mRNA levels observed in the glomeruli of diabetic rats (0.5-fold compared with untreated diabetic rats at 24 weeks [p < 0.01]) but had no effect on increased mRNA levels of TNF-alpha, PDGF-B, TGF-beta, and bFGF. These findings suggest that enalapril therapy may be effective in reducing ET-1 mRNA expression in the glomeruli of diabetic nephropathy.
Animals↗
Endothelin-1 mRNA expression by peripheral blood monocytes in IgA nephropathy.
We investigated endothelin-1 mRNA expression in peripheral blood monocytes from 40 patients with IgA nephropathy, 40 with other glomerulonephritides and 10 with essential hypertension without renal diseases, and from 30 healthy age-matched controls. 95% of patients with IgA nephropathy had increased endothelin-1 mRNA expression in monocytes but little was detected from the other groups. Endothelin-1 mRNA was positively correlated with urinary protein excretion (95% CI 0.835-0.952) and histopathological findings (0.796-0.939). In 15 patients with IgA nephropathy endothelin-1 mRNA values and proteinuria decreased gradually after treatment. Endothelin-1 mRNA-expressing activated monocytes may be associated with the progression of IgA nephropathy.
Adolescent↗
GTP-dependent association of Raf-1 with Ha-Ras: identification of Raf as a target downstream of Ras in mammalian cells.
Ras is involved in signal transduction of various factors for growth, differentiation, and oncogenesis. Recent studies have revealed several proteins that function upstream and downstream of the Ras signaling pathway. However, its immediate downstream target molecular has not yet been identified. In an effort to identify the Ras-associated downstream proteins, we added recombinant Ha-Ras in a GTP-bound form to cell-free lysates and used several antibodies against Ras to immunoprecipitate Ras complexes. We found that a serine/threonine kinase, Raf-1, was coimmunoprecipitated with Ha-Ras by two anti-Ras antibodies (LA069 and Y13-238), whereas a neutralizing antibody against Ras (Y13-259) could not precipitate Raf-1. The coimmunoprecipitation was observed with a complex of Ras and guanosine 5'-[gamma- thio]triphosphate but not with a complex of Ras and guanosine 5'-[beta-thio]diphosphate. The GTP-dependent association of Ha-Ras with Raf-1 was observed with lysates of various types of cultured cells, including NIH 3T3, pheochromocytoma (PC) 12, Ba/F3, and Jurkat T cells, and also with crude extracts from rat brain. Furthermore, Raf-1 was precipitated with a transforming Ha-Ras mutant ([Val12]Ras) and wild-type Ha-Ras but not with an effector-region mutant ([Leu35,ARg37]Ras) that lacks transforming activity. These results indicate that Ras.GTP physically associates with Raf either directly or through other component(s) and strongly suggest that Raf functions in close downstream proximity to Ras in mammalian cells.
3T3 Cells↗
c-Ha-Ras mutants with point mutations in Gln-Val-Val region have reduced inhibitory activity toward cathepsin B.
Protease-inhibitory activity of recombinant Ha-ras gene products (Ras) toward papain and cathepsins B and L was investigated. v-Ha-Ras showed more potent inhibitory activity toward cathepsin B as compared with c-Ha-Ras. We have also investigated protease-inhibitory activity of c-Ha-Ras mutants with point mutations in amino acids between positions 23 and 50. Inhibitory activity of Ras toward papain and cathepsin L was not largely altered among mutants. However, the inhibitory activity toward cathepsin B was significantly impaired by a mutation at position 43, 44, 45 or 48. These results suggest that 43Gln-Val-Val sequence plays an important role at least to inhibit cathepsin B.
Amino Acid Sequence↗
Cellular and intracellular localization of epsilon-subspecies of protein kinase C in the rat brain; presynaptic localization of the epsilon-subspecies.
The cellular and intracellular localization of the epsilon-subspecies of protein kinase C (PKC) in the rat brain was demonstrated by immunocytochemistry using specific antibodies against epsilon-PKC. The epsilon-PKC-specific immunoreactivity was most abundant in the hippocampal formation, olfactory tubercle and Calleja's islands, was moderate in the cerebral cortex, anterior olfactory nuclei, accumbens nucleus, lateral septal nuclei and caudate-putamen and low in the thalamus and medulla. The epsilon-PKC-immunoreactivity was scanty in the perikarya, except for the pyramidal cells of CA3 region of the hippocampus and the immunoreactivity was mainly present in neuropils and nerve fibers. The distribution of epsilon-PKC immunoreactive neurons was consistent with that obtained by in situ hybridization histochemistry. Electron microscopic observations of the hippocampus revealed that the epsilon-PKC is predominantly present in the cytoplasm of axon and nerve terminals and that this enzyme is associated with mitochondrial membrane and vesicles. These results suggested that epsilon-PKC is probably involved in presynaptic functions in CNS, perhaps even neurotransmitter release.
Amino Acid Sequence↗
Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy.
The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.
Blood Glucose↗
Detection of activated platelets in urinary sediments by immunofluorescence using monoclonal antibody to human platelet GMP-140 in patients with IgA nephropathy.
The presence of activated platelets in the urinary sediments was studied by indirect immunofluorescence using monoclonal antigranular membrane protein (GMP)-140 antibody. GMP-140 is generally expressed on the activated-platelets and -vascular endothelial cells. The purpose of the present study was to determine if the presence of activated platelets in the urinary sediments is correlated with glomerular injuries in patients with IgA nephropathy. Fourteen patients with IgA nephropathy and 11 patients with diffuse mesangial proliferative glomerulonephritis without glomerular IgA deposition (PGN) were examined. The number of activated platelets in the urinary sediments was markedly increased in patients in the advanced stage of IgA nephropathy. The ratio of activated platelets to total platelets in the urinary sediments was also increased in such patients. It appears that the detection of activated platelets in the urinary sediments is useful in determining the degree of histological changes in IgA nephropathy.
Adult↗
Messenger RNA expression for growth factors in glomeruli from focal glomerular sclerosis.
Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside (PAN) on Days 0, 27, 34, and 41 and by unilateral nephrectomy on Day 22. Rats were sacrificed on Days 0, 8, and 20 (acute phase) and on Days 48, 60, and 80 (sclerotic phase). The percentage of sclerosing glomeruli was 16.6% on Day 48 and increased significantly to 72.8% on Day 80. We examined glomerular mRNA levels for proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF)-A and B chains, transforming growth factor (TGF)-beta, epidermal growth factor (EGF), insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) on Days 0, 8, 20, 48, 60, and 80. Although these growth factor mRNA levels showed little change in glomeruli until Day 20, all growth factor mRNA levels increased in glomeruli during the sclerotic phase of PAN nephrosis as glomerular sclerosis progressed. On Day 80, mRNA levels for PCNA, PDGF-A and B chains, TGF-beta, EGF, IGF-I, and bFGF increased 12-, 10-, 12-, 15-, 2-, 2-, and 8-fold, respectively, in the glomeruli of PAN-treated rats with marked glomerular sclerosis when compared with control rats. Unilateral nephrectomy without PAN administration did not cause glomerular sclerosis up to Day 80 and mRNA levels for PCNA, PDGF-A and -B chains, TGF-beta, EGF, IGF-I, and bFGF in this group were almost the same as those in the normal sham-operated group. These data suggest that changes in growth factor mRNA levels in glomeruli may contribute to the development of PAN-induced glomerular sclerosis.
Animals↗