Search PubMed⌕ Search

Biomedical subjects

A Fukatsu

Publications and source records attributed to A Fukatsu.

At least 55 records · Page 3Linked to original sources

Surgical treatment of hemodialysis-related shoulder arthropathy.

Thirteen patients with hemodialysis-related shoulder arthropathy were treated either with arthroscopic synovectomy or with open surgery. Arthroscopic synovectomy was performed in eight patients who had shoulder pain, shoulder immobility or both but did not have cystic bone lesions. The therapy was effective for pain relief and improvement of shoulder function for six months but in 12 months the shoulder pain reappeared in most of the patients. Open surgery was done in 5 patients who, in addition to shoulder pain and immobility, had humeral head bone cysts. Resection of the deposited mass on the biceps tendon sheath, of hypertrophied synovium and bursa as well as curettage of cysts and calcium hydroxyapatite ceramic implantation were performed. The therapy was effective for pain relief throughout the follow-up period (12 months). No adverse effects were noted for either procedure. Resected specimens of the synovia contained amyloid as indicated by a positive Congo-red stain by light microscopy and the presence of amyloid fibrils by electron microscopy. Deposition of amyloid in the biceps tendon sheath, synovium and bursa and invasion of the humeral head by amyloid were observed upon open surgery. The results suggest that the resection of deposited material induces the improvement of the shoulder arthropathy.

Amyloidosis↗

Enhanced expression of interleukin-6 in primary human renal cell carcinomas.

We have demonstrated interleukin-6 (IL-6) production by human renal carcinoma cells. The IL-6 gene expression was detected by Northern blot analysis in 22 of 43 primary renal cell carcinoma tissues and in five of seven renal cell carcinoma cell lines. Immunohistochemical analysis confirmed the expression of IL-6 by the tumor cells. Patients with a high-level expression of IL-6 had significantly greater incidences of lymph node metastasis and a larger increase in serum C-reactive protein than those without it. We have also probed for the presence of IL-6 receptor by Northern blot analysis; we detected this receptor in 11 of the 43 primary renal cell carcinoma tissues but in none of the seven renal cell carcinoma cell lines. However, by use of the complementary DNA-polymerase chain reaction, the IL-6 receptor transcript was detected in all specimens, including the seven cell lines. No expression of the interleukin-3 (IL-3) gene was identified in any of the 43 primary renal cell tumors. These data provide evidence that IL-6 and its receptor may play a role in promoting the transformation and/or proliferation of renal cell carcinomas as well as in teh development of symptoms.

Adult↗

Central administration of Lys-D-Pro-Thr, an interleukin-1 beta 193-195 analogue, stimulates feeding in rats.

We determined the effect on feeding of Lys-D-Pro-Thr (LDPT), an interleukin-1 beta 193-195 analogue which antagonizes the analgesic effects of interleukin-1 beta. Intracerebroventricular administration of 2 micrograms/rat LDPT increased food consumption at the 0-1 h time period, although food intake was reduced by LDPT at the 1-2 h time period. There was no effect on colonic temperature 1 h later. Subcutaneously injected LDPT (2 micrograms/rat) failed to increase food intake for 1 h. These data suggest that brain interleukin-1 beta may have a physiological role in feeding suppression.

Amino Acid Sequence↗

Altered ambulatory activity and related brain monoamine metabolism in genetically obese Zucker rats.

Feeding-related behavior and alteration of brain monoamine metabolism were examined in the male lean, and obese Zucker rats. Ambulatory activity of obese rats was reduced in the dark cycle. Dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), contents were significantly decreased in the striatum of obese rats. However, the metabolic rate assessed with the DOPAC/DA ratio, and norepinephrine (EN) content were not changed in the striatum. Hypothalamic DA and NE contents were significantly reduced and the DOPAC/DA ratio was significantly increased in the hypothalamus of obese rats. The present findings suggest that the observed changes in brain monoamine metabolism may contribute to the development of obesity reducing ambulatory activity of obese rats.

3,4-Dihydroxyphenylacetic Acid↗

Formation of subepithelial dense deposits in rats induced by a monoclonal antibody against the glomerular cell surface antigen.

We developed a monoclonal antibody, H5H3, of IgG1 subclass by hybridization technique using spleen cells of mice immunized with plasma membrane fraction of isolated rat glomeruli. H5H3 recognized main bands at about 220 kD by immuno-overlay technique and bound to the glomerulus as well as brush border of proximal tubules by indirect immunofluorescence (IF) microscopy on normal rat kidney frozen sections. By immunoelectron microscopy (IEM) it bound to the surface of mainly glomerular epithelial cell and weakly to the endothelial cell. After injection to Wistar rats it remained granularly in the glomerulus for more than 2 weeks seen by IF. When rats were preimmunized with murine IgG 4 days before the injection of H5H3, mouse IgG, rat IgG and C3 were strongly visible granularly in the glomerulus in 14 days by IF. Numerous dense deposits were formed at subepithelial area seen by transmission electron microscopy. Perfusion experiment of H5H3 into rat left kidney showed granular distribution of mouse IgG in 48 h, indicating that the reaction occurred in situ. H5H3 bound diffusely in fine granular pattern on the surface of cultured glomerular epithelial cells (GEC) studied by IF and IEM. Antigenic redistribution occurred on GEC after incubation of H5H3 at 37 C. These results suggested the required conditions to form subepithelial immune dense deposits, namely that H5H3 after reaction with antigen could stay for long time in the glomerulus; that H5H3 became an antigen in autologous phase to induce large immune complexes; and H5H3 could induce antigenic modulation.

Animals↗

Localization of 20-kD homologous restriction factor (HRF20) in diseased human glomeruli. An immunofluorescence study.

The 20-kD homologous restriction factor (HRF20), which is identical to CD59, is a membrane-associated protein which inhibits the reaction of C9 to form membrane attack complex (MAC) of homologous complements. In various human glomerular diseases deposition of complement components is frequently seen and MAC is reported to associate with immune deposits. Using a specific monoclonal antibody, 1F5, against HRF20, we attempted to study the localization of HRF20 in human glomerulonephritides and to compare the localization of HRF20 with those of immune deposits and MAC. The frozen sections of kidney specimens were fixed in acetone at room temperature before staining. In normal kidneys and kidney specimens from the patients with minimal change nephrotic syndrome, membranous nephropathy, and IgA nephropathy, HRF20 was strongly localized in the peritubular capillaries and along Bowman's capsules. A weaker but well-defined staining was obtained in the mesangial area and faint staining was seen along the glomerular capillary walls. In contrast, glomerular capillary walls were rather strongly stained in the cases with diffuse lupus nephritis which had subendothelial dense deposits. These data suggest that HRF20 (CD59) is present in the human glomeruli and its expression is enhanced under certain conditions such as lupus nephritis.

Antigens, Differentiation↗

Unique glomerular lesion with spontaneous lipid deposition in glomerular capillary lumina in the NON strain of mice.

We found a strain of nonobese, nondiabetic (NON) mice which has spontaneous lipid deposition in glomerular capillary lumina. This strain was developed together with a diabetic strain of nonobese diabetic (NOD) mice for the generation of mouse models of diabetes mellitus. In the NON strain, contrary to the name, impaired glucose tolerance (IGT) was observed in about half of the mice. Meanwhile, peculiar glomerular abnormalities which remotely resemble those of diabetic nephropathy were observed in the NON strain. The lesions were characterized by massive lipid accumulation with proteinaceous material within the glomerular capillary lumina. In addition, positive staining for immunoglobulins, especially IgM, was observed by immunofluorescence microscopy. The overall frequency of this lesion was 91%. Mesangiolysis, capillary ballooning with many small lipid vesicles were the striking features by electron microscopy. Histochemical analysis revealed the presence of various lipids in these lesions. However, as far as we examined, these lesions did not correlate with hyperlipidemia or IGT. Lymphoid follicle-like structures were seen around the renal arterioles. The cellular components of these lymphoid follicles reacted with monoclonal antibodies to L3T4. High levels of serum immunoglobulins were observed in this strain. We suppose that the immunological disorders may have some bearing in the evolution of this lesion in NON mice. We believe that this model may be of use in studying the role of lipid derangements in renal diseases.

Animals↗

A case of angiotropic large cell lymphoma manifesting nephrotic syndrome and treated successfully with combination chemotherapy.

A 52-year-old female had a nephrotic syndrome without neurological or dermatological manifestations. Renal biopsy revealed that glomeruli were filled with tumor cells which bore leukocyte common antigen and pan B cell marker. These cells occupied the capillary lumen and invaded into the mesangial area. Morphological alteration of endothelial cells and glomerular basement membrane were also noticed. The interstitium was well preserved. After five cycles of a combination chemotherapy, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone), the second biopsy revealed that tumor cells disappeared from glomeruli showing mild sclerosis. Proteinuria became absent. This is the first report of an angiotropic large cell lymphoma manifesting a nephrotic syndrome and treated successfully by CHOP therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Distribution of interleukin-6 in normal and diseased human kidney.

Distribution of interleukin 6 (IL-6) in normal and diseased kidneys was examined by an immunohistochemical method. Four specimens of normal kidney tissue and 47 specimens obtained from diseased kidneys by biopsy were studied by indirect immunofluorescence microscopy using specific monoclonal antibody to human IL-6. In the normal kidney, IL-6 was distributed in the glomerular mesangial area and in vascular walls. In the diseased kidneys, IL-6 was observed in the glomerulus in various patterns. The extent of the distribution of IL-6 correlated with the average number of glomerular cells. When sclerosis appeared, the expression of IL-6 decreased. Occasionally, IL-6 was found in the area of synechiae or crescents as well as in the parietal epithelial cells of the glomerulus with synechiae and/or crescents. In the interstitium, IL-6 was seen in atrophic tubules, and the distribution correlated with the extent of tubular atrophy. The binding of anti-IL-6 monoclonal antibody to the renal sections was completely inhibited by preincubation of the antibody with recombinant IL-6. These results suggests that IL-6 expression is a good marker for glomerular cell proliferation and that IL-6 may be involved in the formation of synechiae or crescents and in tubulointerstitial injury.

Antibodies, Monoclonal↗

The kidney disease of Crow-Fukase (POEMS) syndrome: a clinico-pathological study of four cases.

We studied four cases of Crow-Fukase syndrome with renal dysfunction. Kidney specimens obtained by needle biopsy showed glomerular lesions resembling those seen in conditions characterized by microangiopathy. Common glomerular findings by light microscopy were mesangial expansion and narrowing of the capillary lumina. An enlarged subendothelial space and mesangial area with deposition of amorphous material as well as swelling and vacuolization of endothelial cells were observed by electron microscopy. In an active phase, severe mesangial edema and segmental mesangiolysis, and in a late stage, mesangial cell interposition and sclerosis were seen. Tests by immunofluorescence microscopy for the presence of immunoglobulins A, M, G, lambda and kappa light chains, C3, and C4 were negative. Decay accelerating factor was found in glomeruli and in the vascular pole. Other findings included lymph node angiosclerosis, peripheral nerve microangiopathy and hemangioma formation with endothelial cell proliferation. These observations suggest that chronic endothelial injury constitutes the basic pathology of Crow-Fukase syndrome. Hemodialysis was required to manage anasarca in three of the patients although serum creatinine levels were below 5.0 mg/dl. Urinalysis revealed mild abnormalities and did not reflect the severity of the glomerular lesion. Corticosteroids given to three of the patients were effective in controlling fever and the lymphadenopathy; in two cases the corticosteroids induced a recovery of renal function. Thus Crow-Fukase syndrome may be due to chronic endothelial injury; the clinical symptoms and renal involvement respond to corticosteroid therapy.

Aged↗

Histochemical and immunohistochemical studies of diseased human glomeruli.

In order to study the localization of Lentil lectin (LCH)-binding glycoresidues in glomeruli from patients with a variety of glomerulopathies, and to elucidate the relationship between LCH-binding sugars and the components of the extracellular matrix, laminin and type IV collagen, investigations of formalin-fixed, paraffin-embedded kidney tissues digested with trypsin were carried out by the direct and indirect immunofluorescence microscopy techniques. The glomerular basement membrane (GBM) and the mesangium reacted well with LCH, whereas areas with sclerotic lesions exhibited a decreased reactivity. The pattern of LCH binding to the GBM in various glomerulopathies was similar to that of laminin but different from that of type IV collagen. The pattern of localization of LCH-reacting sites and of laminin in the GBM included the double linear lines in diabetic nephropathy, inner linear line with outer projections (spikes) in membranous nephropathy, and reduplicated basement membrane in membranoproliferative glomerulonephritis. The results obtained by enzyme-linked immunoadsorbent assay showed that LCH had a stronger reactivity for laminin than for type IV collagen or fibronectin. These findings suggest that LCH is more reactive with laminin than with other components of the glomerular extracellular matrix.

Carbohydrates↗

Inhibited insulin secretion by recombinant human interleukin-1 beta in adrenalectomized rats: involvement of prostaglandin.

An involvement of prostaglandin synthesis in reduced insulin secretion by interleukin-1 was investigated in adrenalectomized (ADX) rats. The recombinant human interleukin-1 beta (IL-1) significantly reduced insulin secretion in ADX rats 2 and 4 hr after the injection, although IL-1 stimulated insulin secretion in intact rats. In ADX rat, IL-1 showed dose-dependent inhibition of pancreatic insulin secretion. In addition, insulin response to intravenous glucose loading was also attenuated in ADX rats with pretreatment by IL-1. At 4 hours after injection, ibuprofen (IBP; 0.5-50.0 mg/kg, ip), selective cyclooxygenase blocker, attenuated insulin inhibition by IL-1 in a dose-dependent manner. These data suggest that IL-1 may suppress in vivo insulin release at least in part through the mediation of prostaglandin synthesis in the absence of adrenal glands.

Adrenal Glands↗

The significance of decreased ambulatory activity during the generation by long-term observation of obesity in ovariectomized rats.

We attempted to determine the significance of ambulatory activity as a cause of overweight in ovariectomized rats. Drinking and ambulation were measured continuously and directly for periods up to 12 months in special apparatus developed at Gunma University. In older rats, ambulatory activity decreased much more in the ovariectomy group than in the control group. There was no difference in food intake between the ovariectomized and the control group. After 2 months, the ovariectomy group increased body weight more than the control group despite no difference in food intake. The decrease in ambulatory activity was consistent in the ovariectomy group, regardless of any differences in age and body weight. These results indicate that decrease of energy expenditure by gradual decrease in ambulatory activity may be an important factor as a cause of overweight in ovariectomized, obese rats.

Animals↗

The effects of a new immunosuppressive agent, FK506, on the glomerular injury in rats with accelerated nephrotoxic serum glomerulonephritis.

The aim of the present work was to study the effects of a new immunosuppressive drug, FK506, in accelerated nephrotoxic serum glomerulonephritis. Glomerulonephritis was induced in female Wistar rats by the preimmunization with normal rabbit IgG (Day-4) and the subsequent intravenous injection of rabbit anti-GBM serum (Day 0). Without treatment with FK506, rats developed proteinuria at Day 6 and onward. Rat anti-rabbit IgG was strongly detected at Day 6 and the titer was maintained through Day 20. Moderate hypercellularity and focal crescent formation were observed at Day 20. Rats injected intramuscularly with 0.3 or 1 mg/kg of FK506 did not develop proteinuria and the anti-rabbit IgG titer was much less or was undetectable throughout the experiments. These data suggest that FK506 is effective in the present model of glomerulonephritis.

Animals↗

A plasma membrane antigen of rat glomerular epithelial cells. Antigenic determinants involving N-linked sugar residues in a 140-kilodalton sialoglycoprotein of the podocytes.

The aim of the present study was to investigate the antigenic make up of the plasma membrane of rat glomerular visceral epithelial cells (GEP). A crude plasma membrane fraction (PM) was extracted by 1% sodium dioxycholate from isolated rat glomeruli. PM was digested with neuraminidase (NRD) and purified by the Helix pomatia agglutinin (HPA)-affinity column. When studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the HPA-affinity purified plasma membrane fraction (HPA-PM) formed two bands, a main band of 160 kilodaltons (kd) and a smaller band of 40 kd. By Western blot analysis, the antibodies raised in a rabbit against HPA-PM (RbAHPA-PM) reacted only with the 160-kd protein of HPA-PM, or with the relevant 140-kd protein of PM when PM was digested by NRD. The 140-kd protein of PM was reactive with wheat germ agglutinin and, when treated with NRD, was reactive with HPA and peanut lectin. The 160-kd protein of HPA-PM was degraded by endoglycosidase-F and lost its reactivity with RbAHPA-PM. These results suggest that RbAHPA-PM react with antigenic sites involving N-linked sugar residues of a 140-kd sialoglycoprotein, presumably podocalyxin. Immunohistochemical studies using normal rat kidney tissues treated with NRD as substratum showed that RbAHPA-PM bound to the free surface of GEP but not with soles of the foot processes or with other structures of the kidney. In rats intravenously injected with NRD and subsequently with RbAHPA-PM, antibodies were rapidly fixed (within 1 hour) to the free surface of GEP. Immunofluorescence study showed that RbAHPA-PM also reacted with human glomeruli after treatment with NRD. These results suggest that GEP express surface sugar residues that are potential targets for direct immunologic attack.

Animals↗

Experimental glomerulonephritis induced in rats by a lectin and its antibodies.

The aim of the present study was to investigate the events following interaction of antibody with an antigen planted on the surface of glomerular endothelial cell (GEN). A lectin, Helix pomatia agglutinin (HPA), was planted at the surface of rat GEN by the perfusion of the isolated left kidney with neuraminidase (NRD) and HPA. A subsequent perfusion with IgG fraction, but not with Fab fragments, of rabbit anti-HPA serum induced formation of granular immune deposits (IDs) on the surface of GEN. When the left kidney was revascularized after initial formation of IDs, acute glomerulonephritis ensued. Fifteen minutes after revascularization, granular IDs were observed at the subendothelial space. Two days later, there was decrease of subendothelial IDs with concomitant appearance of subepithelial IDs. At the seventh day, IDs were mainly localized in the subepithelial space. The results suggest that this model of experimental glomerulonephritis is characterized by: (1) initial formation of HPA immune complexes (ICs) at the surface of GEN; and by (2) subsequent movement of ICs from luminal side to subepithelial area with local formation of IDs. The results are relevant to the understanding of the kinetics of ICs resulting from interaction of antibodies with exogenous antigens "planted" in the glomerular capillary walls, and of the local formation of IDs.

Animals↗