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Biomedical subjects

Y Yuzawa

Publications and source records attributed to Y Yuzawa.

At least 19 recordsLinked to original sources

A neurofibromatosis type 1 patient with severe kyphoscoliosis and intrathoracic meningocele.

The patient presented with neurofibromatosis and a dystrophic kyphoscoliosis around the cervico-thoracic junction. When the patient was 59 years old, he started to suffer from dyspnea caused by an intrathoracic meningocele in the upper left thoracic cavity. A wide laminectomy from T2 to T5 was performed and the meningocele was resected. Although the dyspnoea disappeared postoperatively, the patient started to neurologically deteriorate. Laminectomy alone caused instability around the apex of the kyphosoliosis and spinal cord compression. Halo cast was applied and brought remarkable recovery of neurologic deficits. This result encouraged us to perform posterior fusion in situ from C3 to L2 with bone graft from the iliac crests and the Luque technique in conjunction with the Isola system. This resulted in the patient being able to walk again. The removal of the posterior element predisposes the patient to unstable postlaminectomy kyphosis and removes valuable bone stock required for posterior spinal fusion. For this reason, spinal fusion should have been conducted during surgery for the patient's meningocele.

Bone Transplantation↗

A case of mucopolysaccharidosis IV with lower leg paresis due to thoraco-lumbar kyphoscoliosis.

We treated a patient of type IV mucopolysaccharidosis (Morquio's disease) with lower leg paresis due to kyphoscoliosis. A 65-year-old woman presented with Morquio's disease. A lateral radiograph demonstrated the classic bullet-shaped vertebrae and a 65 degrees thoraco-lumbar kyphosis. After the age of 60, she suffered from numbness in both lower legs and walking disturbance. Bilateral patellae-tendon reflexes were exaggerated. MRI showed compression of the spinal cord around T12 to L2 with a highlighted area of change inside the spinal cord. Myelography and computed tomography after the myelography showed narrowing of the sub-arachnoidal space and deformation of the spinal cord around the T12 to L2 levels. Severe vertebral osteoporosis made it necessary to first perform posterior correction of the kyphosis and fusion. The curve was stabilised with the Luque method from T7 to L4. Her neurological condition markedly recovered, but 1 year after surgery her neurological condition again began to deteriorate, resulting in walking disturbance. For this reason, anterior decompression and fusion through a lateral thoracotomy was undertaken. Decompression of the spinal cord and a bone graft from the iliac crest were attained. The patient's neurological condition again improved, but not as much as immediately after the first operation.

Aged↗

Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury.

Midkine (MK) is a multifunctional heparin-binding protein and promotes migration of neutrophils, macrophages, and neurons. In the normal mouse kidney, MK is expressed in the proximal tubules. After renal ischemic reperfusion injury, its expression in proximal tubules was increased. Immediate increase of MK expression was found when renal proximal tubular epithelial cells in culture were exposed to 5 mM H(2)O(2). Histologically defined tubulointerstitial damage was less severe in MK-deficient (Mdk(-/-)) than in wild-type (Mdk(+/+)) mice at 2 and 7 days after ischemic reperfusion injury. Within 2 days after ischemic injury, inflammatory leukocytes, of which neutrophils were the major population, were recruited to the tubulointerstitium. The numbers of infiltrating neutrophils and also macrophages were lower in Mdk(-/-) than in Mdk(+/+) mice. Induction of macrophage inflammatory protein-2 and macrophage chemotactic protein-1, chemokines for neutrophils and macrophages, respectively, were also suppressed in Mdk(-/-) mice. Furthermore, renal tubular epithelial cells in culture expressed macrophage inflammatory protein-2 in response to exogenous MK administration. These results suggested that MK enhances migration of inflammatory cells upon ischemic injury of the kidney directly and also through induction of chemokines, and contributes to the augmentation of ischemic tissue damage.

Animals↗

Early-phase enhanced inflammatory reaction after spinal instrumentation surgery.

STUDY DESIGN: The erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and body temperature were measured prospectively in patients after two types of spinal surgery without complications and three cases of infection after spinal instrumentation surgery. OBJECTIVES: To investigate the effects of instrumentation on postoperative inflammatory reaction, and to describe early detection of postoperative wound infection. SUMMARY OF BACKGROUND DATA: In thoracic and abdominal surgery as well as hip arthroplasty, C-reactive protein has proved more valuable than erythrocyte sedimentation rate for early detection of postoperative infectious complications. It has not yet been established, however, how inflammatory parameters change after surgery when spinal instruments have been inserted into the body. METHODS: For this study, two groups of patients were examined: a control group that underwent spinal decompression surgery without instrumentation (n = 36) and another group that underwent spinal decompression and fusion surgery with spinal instrumentation (n = 37). The erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and body temperature were recorded 1 day before surgery and on days 0 to 4, 7, 11, 14, 21, 28, and 42 after surgery. RESULTS: Inflammatory indexes (i.e., C-reactive protein, erythrocyte sedimentation rate, white blood cell count, and body temperature) were significantly higher for the surgery with instrumentation than for the spinal decompression surgery without instrumentation. Multiple regression analysis showed that C-reactive protein and erythrocyte sedimentation rate peaks significantly correlated with the use of instrumentation (C-reactive protein: P = 0.000257, erythrocyte sedimentation rate: P = 0.000132). In the patients with infection after spinal instrumentation surgery, C-reactive protein, white blood cell count, and body temperature started to increase again 4 to 11 days after surgery. The elevation of erythrocyte sedimentation rate levels was prolonged. CONCLUSIONS: Erythrocyte sedimentation rate and C-reactive protein display a significantly higher reaction after spinal surgery with instrumentation. Renewed elevation of C-reactive protein, white blood cell count, and body temperature after postoperative days 4 to 7 may be a critical sign of postoperative infection.

Adult↗

The role of C5a in the development of thrombotic glomerulonephritis in rats.

Thrombus formation is the important pathologic finding observed in glomerulonephritis induced by antiglomerular basement membrane (GBM) antibodies. Although strong deposition of C3 and membrane attack complex (MAC) is observed in this disease, the role of complement has not been fully elucidated. The aim of this work was to investigate the role of complement, especially an anaphylatoxin C5a, in a rat model of thrombotic glomerulonephritis. Rats were first pretreated with subclinical dose of lipopolysaccharide (LPS). Thrombotic glomerulonephritis was then induced by intravenous injection with rabbit antirat GBM (RbAGBM) (Group I). For the evaluation of the role of complement, the soluble complement receptor type 1 (sCR1) (Group II) or the C5a receptor antagonist peptide (C5aR-AP) (Group III) was intravenously administered 30 min before RbAGBM injection. For exploring the role of neutrophils, rats were pretreated with cyclophosphamide before induction of disease (Group IV). All rats were sacrificed at 6 h, and histological examination was performed. Rats in Group I developed severe glomerular thrombosis. Leucocyte accumulation and strong binding of C3 and MAC were observed in the glomeruli. In rats treated with sCR1 (Group II) and C5aR-AP (Group III), both leucocyte accumulation and thrombus formation in the glomeruli were significantly inhibited. C3 and MAC were negative in the glomeruli in Group II rats, while they were strongly observed in Group III. In neutrophil depleted rats (Group IV), there was also deposition of C3 and MAC in the glomeruli but thrombus formation was not observed. These findings indicated that glomerular thrombosis is dependent on the leucocytes, and mediated in part by the anaphylatoxin C5a but not MAC in the present model.

Animals↗

Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis.

BACKGROUND: Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM), is a common histopathological feature of progressive renal disease of diverse etiology. Interaction between transforming growth factor-beta (TGF-beta) and TGF-beta type II receptor (TGF-betaIIR) may play an important role in the ongoing fibrotic process. TGF-betaIIR and TGF-beta have been reported to be up-regulated in human glomerulopathies. In order to block the TGF-beta system, many studies have inhibited TGF-beta itself, but not its receptors. Our study explored the effects of fully human monoclonal antibody against TGF-betaIIR (hTGF-betaIIRAb) on experimental proliferative glomerulonephritis. METHODS: hTGF-betaIIRAb was generated from Xenomice. The expression of TGF-betaIIR was studied by immunohistochemistry in normal and anti-Thy-1 nephritis rats. hTGF-betaIIRAb or control Ab was injected intraperitoneally at day 0 and day 4 of anti-Thy-1 nephritis, and rats were sacrificed at day 7. Effects of hTGF-betaIIRAb were assessed by histological and immunopathological measurements. RESULTS: The specificity of hTGF-betaIIRAb was confirmed by ELISA and Western blot analysis. By immunostaining, TGF-betaIIR expression was up-regulated in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the hTGF-betaIIRAb-treated group, the extent of mesangial expansion was less than that in the control group. By immunohistology, alpha-smooth muscle actin, fibronectin-EDA, and type I collagen were significantly reduced in the hTGF-betaIIRAb-treated group. CONCLUSIONS: Anti-TGF-betaIIR antibody ameliorated ECM accumulation in anti-Thy-1 nephritis. Our data suggest that TGF-betaIIR may be one of the therapeutic targets, and that fully human monoclonal antibody against TGF-betaIIR may have a new therapeutic potential for renal fibrosis.

Actins↗

Effects of a new synthetic selectin blocker in an acute rat thrombotic glomerulonephritis.

In an attempt to explore a novel therapeutic approach, a new synthetic sulfatide derivative (SKK60037) was evaluated in an acute rat model of P-selectin and leukocyte-dependent thrombotic glomerulonephritis (TG). In vitro, SKK60037 inhibits the function of P- and L-selectin more effectively than sialyl Lewis X (sLe(x)), a well-established selectin blocker. TG was induced by the intravenous administration of nephrotoxic globulin (NTG) to rats pretreated with a subclinical dose of lipopolysaccharide. In this model, platelet accumulation was remarkable within 10 minutes after induction of disease, followed by the infiltration of leukocytes, mainly neutrophils and macrophages. Thrombus formation and fibrinogen deposition in the glomeruli were observed within 1 hour, and they proceeded until 6 hours. P-selectin was highly expressed in glomeruli, whereas E-selectin and L-selectin ligands were not detected. We tested the effects of SKK60037 in this model in comparison with sLe(x) and antirat P-selectin monoclonal antibody (ARP2-4). SKK60037 blocked platelet accumulation in glomerular capillaries at 10 minutes after NTG injection. At 6 hours, leukocyte infiltration and thrombosis were significantly suppressed. Protective effects of SKK60037 were similar to those of ARP2-4, whereas sLe(x) showed minimum effect. The superior effects and more favorable characteristics of SKK60037 to sLe(x) suggest the potential of SKK60037 for clinical application.

Animals↗

CD59 protects rat kidney from complement mediated injury in collaboration with crry.

BACKGROUND: As previously reported, the membrane-bound complement regulator at the C3 level (Crry/p65) is important in maintaining normal integrity of the kidney in rats. However, the role of a complement regulator at the C8/9 level (CD59) is not clear, especially when activation of complement occurs at the C3 level. The aim of this work was to elucidate the in vivo role of CD59 under C3 activating conditions. METHODS: Two monoclonal antibodies, 5I2 and 6D1, were used to suppress the function of Crry and CD59, respectively. In order to activate alternative the pathway of complement, the left kidney was perfused with 5I2 and/or 6D1 and was recirculated. RESULTS: In the kidneys perfused with 5I2 alone, deposition of C3 and membrane attack complex (MAC) was observed in the peritubular capillaries, vasa recta, and tubular basement membranes. Cast formation, tubular dilation and degeneration, and cellular infiltration were observed at days 1 and 4, and they recovered by day 7. Further suppression of CD59 by 6D1 significantly enhanced the deposition of MAC and worsened the already exacerbated tubulointerstitial injury. These effects of 6D1 were dose dependent. Perfusion with 6D1 alone did not induce histologic damage or MAC deposition in the tubulointerstitium. CONCLUSIONS: In rats, CD59 maintains normal integrity of the kidney in collaboration with Crry in rats against complement-mediated damage in vivo.

Animals↗

Acute renal failure after a sea anemone sting.

A 27-year-old man suffering from severe swelling and pain in his right arm was referred to our hospital. He showed signs of acute renal failure (ARF) with severe dermatitis of his right arm. Three days before being admitted, he accidentally touched some kind of marine organism with his right hand while snorkeling in the Sulu Sea around Cebu Island. Within a few minutes, he was experiencing severe pain in his right hand. Then his right hand gradually became swollen. The marine creature responsible for this injury was thought to have been a sea anemone, which is a type of coelenterate. Histologic findings of a renal biopsy indicated that acute tubular necrosis (ATN) had caused ARF in this patient's case. Supportive therapies improved renal function of this patient, and steroid pulse therapy attenuated the severe skin discoloration. The ATN was thought to have been caused by the poison from a sea anemone because there were no other conceivable reasons for the patient's condition. This is the first time that a marine envenomation case has been reported in which the sting of a sea anemone has caused ATN without the failure of any other organs.

Acute Kidney Injury↗

Thoracic epidural desmoplastic fibroma.

Desmoplastic fibroma is a relatively uncommon tumor and rarely involves the spine. The authors describe a 20-year-old woman with a thoracic epidural desmoplastic fibroma treated by complete resection and posterior spinal fusion. Four years after surgery, neither the tumor nor clinical symptoms have recurred. Thus, complete resection is considered necessary to treat this tumor.

Adult↗

Neointima formation in a restenosis model is suppressed in midkine-deficient mice.

Neointima formation is a common feature of atherosclerosis and restenosis after balloon angioplasty. To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation. MK expression increased during neointima formation caused by intraluminal balloon injury of the rat carotid artery. Neointima formation in a restenosis model was strongly suppressed in MK-deficient mice. Continuous administration of MK protein to MK-deficient mice restored neointima formation. Leukocyte recruitment to the vascular walls after injury was markedly decreased in MK-deficient mice. Soluble MK as well as that bound to the substratum induced migration of macrophages in vitro. These results indicate that MK plays a critical role in neointima formation at least in part owing to its ability to mediate leukocyte recruitment.

Angioplasty, Balloon↗

Eosinophilic granuloma of the spine: early spontaneous disappearance of tumor detected on magnetic resonance imaging. Case report.

Two cases of eosinophilic granuloma (EG) of the spine associated with neurological deficits are presented. The patients were treated conservatively by using external fixation with a brace as well as bed rest. Neurological deficits and pain diminished and finally disappeared as the tumor mass decreased in size, as seen on magnetic resonance (MR) imaging. During the 5-year follow-up period no recurrence of the tumors was detected on MR images. Surgical treatment for spinal EG in children presenting with typical vertebra plana is not recommended except for those with severe or progressive palsy and for those in whom the disease requires differential diagnosis.

Cervical Vertebrae↗

Experimental spinal fusion with use of recombinant human bone morphogenetic protein 2.

STUDY DESIGN: Posterolateral lumbar spinal fusion with use of recombinant human bone morphogenetic protein 2 (rhBMP-2) was tested in rabbits by implanting composites of rhBMP-2 and collagen carrier. OBJECTIVES: To examine the bone-formation-inducing activity of rhBMP-2 and find the optimal amount of rhBMP to add to a collagen carrier to constitute bone-formation-inducing implants to be substituted for bone graft in posterolateral spinal fusion in rabbits. SUMMARY OF BACKGROUND DATA: In animal models, rhBMP-2--impregnated collagen has been successfully used for posterolateral spinal fusion, indicating that it is a potential substitute for the autogenous corticocancellous bone graft currently used most routinely in posterolateral lumbar spinal fusion. METHODS: Nine rabbits were divided into three equal groups. The bilateral L4-L5 transverse processes were exposed, and collagen strips impregnated with rhBMP-2 (10, 50, or 200 micrograms) were placed on the left transverse processes, and collagen strips alone were inserted on the right. All rabbits were killed 24 weeks after surgery. The implanted sites were assessed for new bone formation and bony fusion by radiography and histologic examination. RESULTS: New bone formation was noted in intertransverse spaces on the left side of all rabbits except one (10 micrograms rhBMP-2). Twelve weeks after implantation, no new bone formation was seen on the right side of all animals. The newly formed bone masses were significantly larger in the 50-microgram and 200-microgram rhBMP-2 groups than in the 10-microgram rhBMP-2 group (P < 0.01), but there was no significant difference between bone formation in the 50-microgram and 200-microgram groups (P = 0.647). CONCLUSIONS: The rhBMP-2/collagen composite implant was an effective bone graft substitute for achieving posterolateral spinal fusion. When combined with a collagen carrier, the optimal rhBMP-2 dose for achieving posterolateral spinal fusion seemed to be approximately 50 micrograms per segment in rabbits.

Animals↗

Nontraumatic lumbar vertebral compression fracture as a risk factor for femoral neck fractures in involutional osteoporotic patients.

To screen a potential risk factor for femoral neck fracture, we characterized lumbar vertebral fractures in 120 patients with femoral neck fractures (19 men, 101 women; mean age, 78.7 years) by investigating the frequency of patients with lumbar vertebral fracture, the number of vertebral fractures per patient, and the severity of deformity of the fractured vertebral bodies. These findings were compared with data gathered from a population of age- and sex-matched control patients (20 men, 89 women; mean age, 77.6 years) who had no evidence of femoral neck fracture. The heights of the anterior and posterior walls together with the midpart of the lumbar vertebrae were measured on lateral radiographs to identify fractures. The extent of height loss in the fractured vertebrae was calculated for each group. The incidence of patients with vertebral compression fractures was significantly higher in the femoral neck fracture group than in the control group (65.0% vs 41.1%). In terms of age, the difference in the incidence of vertebral fractures in the two groups was greater in the less aged (60-79 years old) than in the more aged (>80 years old) population. The mean number of lumbar vertebral fractures was also significantly greater in the femoral neck fracture group than in the control group (1.59 +/- 1.39 vs 0.75 +/- 1.19; P < 0.001). The incidence of more deformed vertebral fractures, which were defined as a vertebral height loss of more than 50%, was also significantly higher in the group with femoral neck fracture than in the control group (23.0% vs 7.3%). Based on these results, we concluded that multiple and more severely deformed vertebral fractures might represent a high risk for femoral neck fracture, particularly in patients less than 79 years of age. Care measures that encompass fall prevention and protection of proximal femurs in addition to drug therapy for osteoporosis should be recommended to individuals in this category.

Age Factors↗

Spatially and temporally regulated expression of N-acetylglucosamine-6-O-sulfotransferase during mouse embryogenesis.

GlcNAc-6-O-sulfotransferase is involved in formation of 6-sulfo-N -acetyllactosamine-containing structures such as 6-sulfo sialyl Lewis x. We investigated the mode of expression of GlcNAc-6-O-sulfotransferase during postimplantation embryogenesis in the mouse by in situ hybridization. Sulfotransferase mRNA was not detected on embryonic day (E) 6.5, while on E7.5 it was detected in the mesoderm, ectoderm, and ectoplacental cone. On E10.5, the sulfotransferase signals were mainly observed in the nervous tissue. On E12.5 and 13.5, various tissues in the process of differentiation expressed this mRNA. Several epithelial and mesenchymal tissues undergoing epithelial-mesenchymal interactions strongly expressed the mRNA. For example, in the developing tooth strong sulfotransferase mRNA expression was found only in the condensing mesenchyme on E13.5. On E13.5 and 15.5, the sites showing intense expression of the sulfotransferase again became restricted. In the brain, sulfotransferase mRNA was frequently found as discrete signals in narrow regions. These results suggest that 6-sulfo-N-acetyllactosamine structures have important roles in development. On E13.5 and 15.5, G152 (6-sulfo sialyl Lewis x antigen) was expressed in the neocortex, and AG223 (6-sulfo Lewis x antigen) in the thalamus and neocortex where the sulfotransferase signal was detected. However, in other organs, expression of these antigens did not correlate with the sulfotransferase mRNA, implicating complex nature of regulation of expression of the fucosyl 6-sulfo antigens.

Animals↗