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Biomedical subjects

S Takebayashi

Publications and source records attributed to S Takebayashi.

At least 109 records · Page 6Linked to original sources

An analysis of monocyte/macrophage subsets and granulocyte-macrophage colony-stimulating factor expression in renal allograft biopsies.

The role of infiltrating macrophages in the pathogenesis of acute rejection was investigated in biopsy specimens obtained from human transplanted kidneys using immunohistochemical methods. Thirty-one allograft tissue specimens obtained from 26 patients were histologically classified into 18 with acute rejection, 7 with borderline change and 6 with chronic rejection according to the Banff working classification (1993). These specimens were analyzed by avidin-biotin peroxidase complex method on frozen sections in order to examine the utility of some antimonocyte/macrophage monoclonal antibodies in differentiating acute rejection from other conditions. The ratio of CD68, CD11b, LeuM3, OKM5 and HAM56-positive infiltrating monocytes/macrophages to leukocyte common antigen (LCA)-positive cells in the renal cortex were calculated. As a result, the ratio of the positive cells for CD68, which stains mature macrophages, significantly increased in the cases of acute rejection compared with those of other groups. In addition, a strong expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed in the acute rejection group. In our study, the expression of class II major histocompatibility antigens (HLA-DR) in the proximal epithelial tubules was also strongly observed in the cases of acute rejection. It was thus concluded that the increase of CD68-positive infiltrating cells and the expression of GM-CSF may play a possible role as a reaction effector in the process of acute renal allograft rejection.

Adolescent↗

Glomerular hypertrophy in relapsing minimal change nephropathy.

Clincopathological and morphometric analysis of glomerular hypertrophy was conducted using biopsies from 89 patients with minimal change nephrotic syndrome (MCNS). Of the 80 patients, in 69 with complete remission and in 20 with one or more relapses, various clinical and morphometric parameters were compared to 15 normal controls. Proteinuria was more severe and serum creatinine (Cr) concentration significantly higher in patients with relapse of proteinuria. The morphometric analysis showed that the sizes of (1) glomerular tufts and (2) glomerular capillaries were significantly larger in patients in the relapse group than in the remission or control groups, but no difference in the size of Bowman's capsule was found between the two MCNS subgroups. The intertubular capillaries were narrower in patients who failed to reach prompt complete remission. A negative correlation between intra- and extraglomerular capillary size was evident (r = -0.83, p < 0.001). A definitive correlation was detected between the circumference of glomerular capillary loops and the degree of proteinuria (r = 0.89, p < 0.001). The mean tubulocapillary diffusion distance was significantly longer in biopsies of the patients in relapse and showed a close significant correlation with serum Cr level (r = -0.87, p < 0.001) and intertubular capillary size (r = -0.87, p < 0.001). These data suggest that extra- and intraglomerular hemodynamic alterations in MCNS lead to glomerular hypertrophy, and dilatation of the glomerular capillary loop plays a key role in the relapse of MCNS.

Adolescent↗

Advanced glycation end products of the Maillard reaction in aortic pepsin-insoluble and pepsin-soluble collagen from diabetic rats.

Recent immunohistological studies using antibodies against advanced glycation end products (AGEs) have demonstrated the presence of AGEs in several tissues. By an enzyme-linked immunosorbent assay using the monoclonal anti-AGE antibody, the present study aimed to determine AGEs in pepsin-insoluble collagen (PIC) as well as in pepsin-soluble collagen (PSC) from the aortas of streptozotocin (STZ)-induced diabetic rats (at 4, 16, and 28 weeks after STZ injection) and those of age-matched control rats. Addition of EDTA to the immunoassay buffer has led us to successful determination of AGEs in the aortic PIC samples with following results: 1) in diabetic rats, there was a time-related increase in the AGE contents at 28 weeks (n = 9, 226.4 +/- 13.5 ng/mg collagen [mean +/- SE]), compared with that at 4 and 16 weeks (n = 6, 79.6 +/- 9.5 ng/mg collagen, and n = 8, 149.4 +/- 30.9 ng/mg collagen at 4 and 16 weeks, respectively; both P < 0.05, between 4 and 16 weeks and 28 weeks); 2) after 28 weeks of diabetes, the AGE contents in PIC of aortas were significantly higher in diabetic rats than in controls (n = 9, 226.4 +/- 13.5 ng/mg collagen vs. n = 8, 129.6 +/- 14.9 ng/mg collagen, P < 0.01, diabetic vs. control); and 3) the level of the AGE content was strongly correlated with the PIC/total collagen (TC) ratio (n = 45, r = 0.698, P = 0.0001). By treating the samples of PSC with alkaline solution, the AGE content of PSC was also determined. In the PSC fraction, the AGE levels in the diabetic rats tended to increase with time and to be higher than those of control rats at 28 weeks although these changes were not statistically significant (diabetic: n = 4, 19.4 +/- 9.7; n = 6, 22.3 +/- 6.2; n = 6, 39.6 +/- 10.8; control: n = 4, 19.7 +/- 9.8; n = 6, 22.9 +/- 7.3; n = 7, 30.7 +/- 7.2; at 4, 16, and 28 weeks, respectively). Compared with the AGE levels of PSC, those of PIC were about four to seven times and four to five times higher in diabetic and control rats, respectively (PIC versus PSC in diabetic or control rats, all P < 0.001, at 4, 16, and 28 weeks, respectively). These findings provide the first immunochemical evidence that AGE adducts are present in the materials extracted sequentially by pepsin and collagenase and that these adducts in PIC accumulated as a function of the increase in the aortic PIC/TC ratio.

Animals↗

The clinico-pathological characteristics and outcome in hemolytic-uremic syndrome of adults.

Twenty-eight adults who developed hemolytic-uremic syndrome (HUS) underwent a renal biopsy during the period from 1973 to 1993, and the specimens were analyzed both clinically and pathologically. The observed etiologic antecedents of HUS were infectious disease in 7 cases, medication, mainly due to cytotoxic drugs in 7 cases, post-partum in 7 cases, progressive systematic scleroderma in 1 case and unknown in 6 cases. Histologically, 17 cases were glomerular type, 3 cases were arterial type, 6 cases were mixed type and 2 cases demonstrated cortical necrosis. The preceding conditions and the histological findings appeared not to be related to each other. In the acute phase of the disease, of 11 patients who fell into severe acute renal failure (ARF) with an increase in the serum creatinine level of more than 5 mg/dl, 8 patients needed dialysis therapy while 4 patients did not recover from the disease (3 died and 1 was introduced to maintenance dialysis therapy). The incidence of thrombus in the glomerular capillaries and fibrinoid necrosis of the arterioles, the index of the expansion of glomerular subendothelial lucent zone (Glom-SE-ex), the index of glomerular sclerosing and the index of the intimal thickening of the arterioles were higher in the severe ARF than in the mild ARF. After analyzing the prognostic factors on renal survival, severe ARF, the presence of fibrinoid necrosis, severe glomerular endothelial damage and severe intimal thickening of the arterioles appeared to have a significantly adverse effect. Moreover, high Glom-SE-ex and the presence of fibrinoid necrosis also independently influenced renal survival. We thus conclude that the etiology of HUS in adults demonstrates a greater variation than that in children. Therefore, it is very difficult to predict the outcome of this disease based on the clinical findings alone, and thus a renal histological examination is considered to help in determining the long-term outcome.

Acute Kidney Injury↗

[A patient with Goodpasture's syndrome revealed a poor prognosis regardless of receiving intensive therapy from an early stage after onset].

Goodpasture's syndrome has been reported as a disease that has a favorable prognosis when the patient receives intensive immunosuppressive drug-therapy from an early stage after onset. The present report describes a 50-year-old woman, who exhibited progressive renal failure accompanied by pulmonary hemorrhage, and an increase in serum level of antiglomerular basement membrane (GBM) antibody. Initial histological examination of a renal specimen indicated a severe fibrocellular crescentic glomerulonephritis with a linear deposition of Ig-G and C3 along the glomerular capillary wall. The patient was thus diagnosed as having Goodpasture's syndrome. Therapy with pulse treatment of steroid (corticosteroid hormone), immunosuppressive agents, or plasma-exchange for the removal of anti-GBM antibody was adopted a week after the clinical onset. However, histological amelioration of the glomeruli did not occur with this treatment in the second biopsy, while glomerular damage advanced progressively. In contrast to other patients with Goodpasture's syndrome, our case revealed an unfavorable outcome regardless of receiving intensive therapy from an early period after onset, which suggests that more intensive therapy of another approach to this patient may have been necessary.

Anti-Glomerular Basement Membrane Disease↗

[New surgical technique of anterior decompression for cervical disc disease: vertebral column autograft with the intervertebral disc after anterior cervical decompression].

The authors describe the surgical technique of vertebral column autograft with the intervertebral disc after anterior decompression for cervical disc disease. This series consisted of 41 patients with cervical disc disease suffering from cervical spondylotic radiculomyelopathy. There were 27 men and 14 women, ranging in age from 27 to 72 years (mean age 49 years). 33 patients were operated on at one level and 8 patients at two levels. The average postoperative follow-up period was one year 10 months and ranged from 6 months to 3 years 3 months. The patients were generally allowed out of bed wearing a soft collar within 1 day postoperatively. The collar was used for 2 months after surgery. The postoperative course of all patients was uneventful and neurological symptoms improved. Postoperative X-ray films showed some movement in the operated disc level in all patients. The authors think that this surgical procedure may be suitable for preserving mobility of the spine.

Adult↗

Oxidized low density lipoprotein stimulates collagen production in cultured arterial smooth muscle cells.

We examined the interactive effect of oxidized low density lipoprotein (LDL) and ascorbic acid on collagen production in cultured smooth muscle cells (SMCs). Porcine aortic SMCs were incubated with 50-200 micrograms/ml of human LDL with/without 5 microM Cu2+ for 24 h. Collagen production was assayed by successive salt precipitation at acidic and neutral pH after pepsin digestion of 3H-proline-labeled collagenous protein. Oxidation of LDL was evaluated by electrophoresis and by the level of thiobarbituric acid reactive substances (TBARS). Ascorbic acid reduced the oxidation of LDL + Cu2+ (53% reduction). In the presence of ascorbic acid, no differences were noted in collagen production between LDL and LDL + Cu2+. Without ascorbic acid, collagen production with LDL + Cu2+ was increased dose-dependently up to 6-fold with 150 micrograms/ml LDL, while no such effects were observed at any doses of native LDL. The addition of butylated hydroxytoluene to LDL + Cu2+ strongly suppressed oxidation (88% reduction), and significantly reduced collagen production close to that seen with native LDL. These results indicate that oxidized LDL stimulates collagen production in SMCs, while native LDL does not. Therefore, oxidized LDL may play a direct role in stimulating collagen production in SMCs, which could lead to collagenosis in atherosclerosis.

Animals↗

Nonenzymatic glycation and extractability of collagen in human atherosclerotic plaques.

The relationship between the extractability of collagen by enzymatic digestion and the degree of nonenzymatic glycation of collagen was examined in the aorta and skin from 38 subjects without diabetes mellitus (mean age: 62.3 +/- 20.2 years). Samples were obtained from the aortic media (M), lesion-free intima (I), atherosclerotic intima (A) and dermis of the skin (S). Collagen was extracted first by incubation with 1/50 (enzyme/substrate weight ratio) pepsin at 4 degrees C for 24 h (P-fraction) and then by incubation with 1/10 (enzyme/substrate weight ratio) pepsin at room temperature for 24 h (EP-fraction). The pepsin-insoluble precipitates were digested by incubation with 270 units of bacterial collagenase at 37 degrees C for 24 h (PIS-fraction). Collagen contents, ketoamines and collagen-linked fluorescence (CLF) were measured in each fraction. The amount of ketoamines and the level of CLF correlated inversely with the susceptibility of collagen to pepsin digestion in various tissues, including M, I, A and S. These values were highest in both the P- and EP-fractions of M, which contained the least amount of collagen extracted by pepsin digestion. In contrast, they were lowest in S, where the concentration of collagen extracted by pepsin digestion was greatest among all of the tissue samples. Atherosclerotic intima (A) and aortic media (M) showed an age-related increase in the total amount of collagen digested with pepsin and collagenase, which depended mainly on an increase in the content of pepsin-insoluble collagen. Although the total amount of collagen did not increase with advancing age in I or S, collagen in I and S became progressingly resistant to pepsin digestion. These results suggest that the age-related decrease in the susceptibility of collagen to pepsin digestion may be due to nonenzymatic glycation in atherosclerotic lesions as well as normal tissues, including the aortic media, lesion-free intima and skin. The level of CLF significantly increased with age in the P-fraction and/or EP fraction of M, I and S. However, there was no relationship between the level of CLF and the subject's age in A. Thus, the accumulation of advanced glycation endproducts (AGEs) on collagen fibers may be partially responsible for the increase in collagen matrix in atherosclerotic lesions of subjects without diabetes mellitus.

Adolescent↗

Sonographic findings in muscle strain injury: clinical and MR imaging correlation.

Both sonography and magnetic resonance imaging were performed in 57 patients with clinically suspected strain injury in lower extremity muscles. Sonography demonstrated normal findings in nine patients (16%), hyperechoic infiltration in 31 patients (54%), mass in nine patients (16%), and compound lesions of infiltration and mass in eight patients (14%). Clinically grade 2 lesions ranged from small infiltration to large compound lesions on both sonography and magnetic resonance imaging. Hyperechoic infiltration was not demonstrated on T1-weighted magnetic resonance images and with less than 50% cross-sectional muscle involvement. The mass and compound lesions were ascertained to be moderate or severe injury because the masses of the lesions had obvious hemorrhage or hematoma on magnetic resonance images.

Adolescent↗

[Histopathology of the biopsied kidney and its related glomerular deterioration].

This paper presents the incidence of glomerulonephritis (-pathy: GN) from a large number of more than 10,000 serial renal biopsies examined in one laboratory using the same criteria over the past 25 yrs. in Japan. Each incidence is as follows: IgA nephropathy (IgAN), 33%; thin glomerular basement membrane disease (TBMD), 17.8; athletic pausal urinary abnormality (APUA), 8.2; primary membranous glomerulonephritis (memb GN), 6.5; while all others were less than 5% each. Out of 3,300 IgAN cases, 51% consisted of a minimal change IgAN (MCIgAN), while the IgAN cases with moderate to severe glomerular damage comprised 20% of all cases. In addition, the survival curves of the IgAN cases coincided with those of FGS and benign nephrosclerosis (BNS) with a similar extent of glomerular damages. On the other hand, glomerular damage mostly occurred due to intra- and intercapillary cell infiltration; poststreptococcal GN (AGN), lupus N, Cat. III a IV a and IV b, and MCIgAN all had a favorable outcome (follow-up mean: 12.4 +/- 6.7 yrs). More than 50% of the dialized patients came from both IgAN, focal type with hypertension, and IgAN with more than moderate glomerular damage regardless hypertension. The incidences of AGN, MPGN, HBvN have all decreased at the present time, while renal amyloidosis and crescentic glomerulonephritis (Cres. GN) have increased in number and this is reflected by the increased number of renal biopsies in elderly men. Glomerular deterioration is thus considered to be caused more by non-immunologic and hemodynamic injuries than by immune-derived, repeated inflammation, in human chronic glomerulonephritis(-pathy).

Biopsy↗

[Aging of aorta and atherosclerosis--role of nonenzymatic glycation of collagen].

In order to clarify the role of the nonenzymatic glycation of the collagen matrix in aging of the aorta and atherogenesis, we studied the relation between ketoamine or advanced glycation end-products (AGEs) and the solubility of collagen in human skin and aorta. AGEs were measured as a collagen-linked fluorescence (excitation wavelength: 370 nm. emission wavelength: 440 nm). There was a positive correlation between the level of AGEs and subjects' age in skin and aortic media. Collagen became more insoluble with increase in the amount of ketoamine and AGEs. Collagen was more resistant to pepsin digestion in atherosclerotic intima than in other tissues including aortic media, lesion-free intima and skin. Diabetic rats showed an accumulation of collagen in aortic media at 28 weeks after an injection of streptozotocin. Moreover, they increased the percentage of insoluble collagen to total collagen and the amount of AGEs binding to insoluble collagen in aortic media. In contrast, the amount of ketoamine of insoluble collagen was increased in diabetic rats at 16 weeks as compared to control. There was no difference in DNA contents of cultured smooth muscle cells between glycolaldehyde-modified and non-modified matrices. However, the activity of type I collagenase (inactive form) of smooth muscle cells decreased on glycolaldehyde-modified type I collagen as compared to that on non-modified collagen. These results suggest that AGEs contribute to the accumulation of collagen in atherosclerotic lesions and aged aorta through the insolubility of collagen and the inhibition of collagenase activity of smooth muscle cells.

Adult↗

The development of noradrenaline-, acetylcholinesterase-, neuropeptide Y- and vasoactive intestinal polypeptide-containing nerves in human cerebral arteries.

The development of cerebrovascular nerves containing noradrenaline (NA), acetylcholinesterase (AChE), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in the basilar artery was histochemically or immunohistochemically studied in human fetuses of various gestational ages. At the 12th week of gestation, nerve fibers containing NA and AChE appeared. Both types of nerve fibers consisted exclusively of the longitudinal nerve fibers (LNF) running along the basilar arteries. Subsequently, the circular nerve fibers (CNF) gradually increased and such development was then completed by the 20th week of gestation. NPY- and VIP-containing nerve fibers were detected in human fetal cerebral arteries in the 16th week of gestation, in the form of LNF. Subsequently, CNF gradually increased and development was completed by the 24th week of gestation. These results indicate that neuropeptide-containing nerve fibers, together with NA- and AChE-containing nerves, therefore contribute to the control of cerebral circulation in the later stages of embryogenesis in human cerebral arteries.

Acetylcholinesterase↗

PDGF-like growth factor from SV40-transformed smooth muscle cells promotes growth in an autocrine or paracrine manner.

We investigated the growth characteristics of smooth muscle cells transformed by oridefective simian virus 40 plasmid DNA (TSMCs). TSMCs demonstrated a significantly higher proliferative activity when compared with nontransformed smooth muscle cells (SMCs). The SMCs were not able to proliferate in media with 5% plasma-derived serum (PDS) instead of fetal bovine serum, while TSMCs grew under this condition. When the DNA synthesis of quiescent SMCs was reinitiated by the addition of serum or platelet-derived growth factor (PDGF), the amount of [3H]thymidine incorporation into DNA varied with the concentrations of serum or PDGF and decreased on type V collagen compared with the other collagen substrates. In contrast, the TSMCs showed no differences in the amount of [3H]thymidine incorporation into DNA among the various concentrations of serum or PDGF and different types of collagen. When quiescent SMCs were cocultured with TSMCs, they showed a remarkable increase in the amount of [3H]thymidine incorporation into DNA, which was most intensively inhibited by type V collagen. These results suggest that TSMCs can promote the growth of TSMCs and SMCs in either an autocrine or paracrine manner and that they proliferate independently of the collagen matrices. Trapidil, a pyrimidine derivative that may inhibit the action of PDGF, decreased the number and cAMC levels of TSMCs in the media with 5% PDS in a concentration-dependent manner. The addition of polyclonal anti-PDGF-B antibody induced up to 59.5% inhibition of enhancement of DNA synthesis of SMCs cocultured with TSMCs. The level of cyclic adenosine monophosphate (cAMP) increased in the TSMCs compared with the SMCs. There was, however, no difference in the cAMP levels of either cells between the various types of collagen. Thus, the release of PDGF-like growth factor and an accumulation of cellular cAMP may be related to an increased DNA synthesis of TSMCs.

Animals↗

Factors contributing to the outcome in 100 adult patients with idiopathic membranous glomerulonephritis.

Follow-up data on 100 patients with idiopathic membranous glomerulonephritis (IMGN), in whom renal biopsy has been performed, are discussed. The period of follow-up ranged from 3 to 24 years (median 7.8 years). Sixteen of the patients had end-stage renal disease. Complete remission of renal disease occurred in 41 patients. The remaining 43 patients exhibited persisting renal functional abnormalities at the end of the follow-up period. Using Cox's proportional hazard model, six parameters were found as predictive factors for prognosis at the time of biopsy: serum cholesterol level > 260 mg/dl, serum creatinine concentration > 1.4 mg/dl, the presence of tubulointerstitial (TI), vascular, mesangial, and Bowman's capsular lesions. No effect was observed in the size of subepithelial electron dense deposits (SED) on prognosis. A weakly positive correlation was found between the thickness of the glomerular basement membrane (GBM) and poor outcome. Treatment with steroid and/or immunosuppressive agents was not found to improve survival. Assessment of these factors thus allows the pathologist to make a relevant statement concerning the probable course and prognosis of the disease at the time of the diagnostic biopsy.

Adult↗

Low density lipoproteins bind more to type I and III collagens by negative charge-dependent mechanisms than to type IV and V collagens.

The accumulation of low density lipoprotein (LDL) in the arterial intima is an important characteristic of atherosclerosis. We investigated the mechanisms by which LDL binds to different types of collagen. The binding activities of 125I-labeled human native LDL (nLDL) and copper-oxidized LDL (oxLDL) with different collagen gels prepared in type I collagen-based mixtures with types I, III, IV and V (I+I, I+III, I+IV and I+V, respectively) were examined. A concentration of 20 micrograms LDL protein/150 micrograms collagen/well was used. The diffusion of both nLDL and oxLDL into the collagen gels reached an equilibrium after 48 h. All of the collagen gels showed the same rates of diffusion with both LDLs. The binding activities of oxLDL were significantly greater than those of nLDL (P < 0.001%), while the binding activities for both LDLs followed the order I+I and I+III > I+V > I+IV. However, the increased binding rate of oxLDL compared to nLDL was 1.66 for I+IV, 1.50 for I+V, 1.33 for I+I and 1.19 for I+III. When a 10-fold higher dose of NaCl (1 M) was added to the oxLDL medium, the binding rate of oxLDL was reduced (rate of reduction: 52% (I+I), 48% (I+III), 35% (I+IV), 13% (I+V)). These results suggest that oxLDL binds more to type I and III collagens by negative charge-dependent mechanisms than to type IV and V collagens. Therefore, types I and III collagens may play an important role in trapping LDL, especially oxLDL. Therefore, oxidatively modified LDL may contribute to atherogenesis due to its longer retention in the arterial wall.

Arteriosclerosis↗