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Biomedical subjects

N Sugano

Publications and source records attributed to N Sugano.

At least 91 records · Page 5Linked to original sources

Arg-Gly-Asp(RGD) peptides inhibit Streptococcus mitis to adhere to fibronectin.

Fibronectin (Fn) is a multifunctional adhesive protein found on cell surfaces as well as in plasma. It is also believed to play an important role in bacterial adherence to host tissues. Molecular analyses of Fn have shown that the amino acid triplet arginine-glycine-aspartic acid (RGD) sequence functions as a binding site. We examined the role of the RGD sequence on bacterial adherence to Fn. The pretreatment of Streptococcus mitis with synthetic RGD-containing peptide reduced the number of bound bacteria to the Fn coated plates by 76%. In contrast, a control peptide containing the RGE sequence showed no inhibition. These data indicate that synthetic RGD peptides may be useful for the inhibition of bacterial adherence to Fn on host cell surfaces.

Amino Acid Sequence↗

Contralateral hip in patients with unilateral nontraumatic osteonecrosis of the femoral head.

To clarify the risk of the development of osteonecrosis of the femoral head in the contralateral hip of patients with unilateral nontraumatic osteonecrosis of the femoral head, a followup study was performed using magnetic resonance imaging. Forty-six asymptomatic contralateral hips with no evidence of osteonecrosis on magnetic resonance imaging, in patients with unilateral osteonecrosis, were subjects of this study. The period from the onset of unilateral osteonecrosis to entrance in this study ranged from 1 month to 20 years (mean, 3.1 years). There were 29 males and 17 females ranging in age from 16 to 71 years (mean, 41 years). Twenty-three patients had previous steroid therapy for various conditions: 16 had alcoholism and 7 had no etiologic factors. The followup term ranged from 3 to 8 years (average, 5.5 years). During the followup period, 1 patient (2%) had a band of low signal intensity demarcating the lesion of normal fat intensity on T1 weighted images, which progressed to collapse of the femoral head. These results suggest that in unilateral osteonecrosis cases, osteonecrosis rarely develops in the contralateral hip that has appeared normal on magnetic resonance imaging. The contralateral hip with a negative magnetic resonance imaging scan is not in Stage 0 of osteonecrosis, but is normal.

Adolescent↗

[Cisplatin/5-fluorouracil intraperitoneal administration superior to intravenous administration for liver metastases of colonic carcinoma].

A 28-year-old female underwent sigmoidectomy for sigmoid colon cancer with peritoneal seeding. One month later, a solitary metastasis was found in S3 of the liver. After CDDP/5-FU intravenous chemotherapy, another metastasis appeared in S7. Intravenous administration showed PD. But the metastatic tumors shrank and became inobservable by CT after the 1st round of CDDP/5-FU intraperitoneal chemotherapy, and S7 tumor could not be identified after the 2nd round. Many previous reports demonstrated the concentration of cytotoxic drug in intraperitoneal administration was much higher than in intravenous administration. Theoretically, intraperitoneal chemotherapy is superior to intravenous chemotherapy for the prevention and treatment of liver metastases. This case demonstrated this hypothesis was right. We think adjuvant intraperitoneal chemotherapy should be re-considered for the prevention of the liver metastases of gastrointestinal cancers.

Adenocarcinoma↗

[Experimental study on intraperitoneal sequential MTX/5-FU therapy for peritoneal seeding in comparison with intravenous administration].

Sequential MTX/5-FU therapy (intravenous route) is powerful chemotherapy especially for poorly differentiated adenocarcinoma of the stomach and its peritoneal metastases. The authors had proposed the idea of intraperitoneal sequential MTX/5-FU chemotherapy for potential peritoneal metastases and micrometastases from advanced gastric carcinoma. This experimental study was planned to confirm this experimentally. Peritoneal seeding model of nude mice was made by the intraperitoneal inoculation of human gastric cancer cell line MKN-45. Control group (n = 5) had no treatment. The intraperitoneal (i.p.) group and intravenous (i.v.) group underwent the treatments on the 7th, 14th, and 21st day after cell implantation. Experimental chemotherapies consisted of intraperitoneal injection of MTX (15 mg/kg, 1.5 ml saline) and 5-FU (50 mg/kg, 1.0 ml saline) for i.p. group and intravenous injection of MTX (15 mg/kg, 0.2 ml saline) and 5-FU (50 mg/kg, 0.2 ml saline) for i.v. group. Interval time between MTX and 5-FU administration was 2 hours. On the 35th day after the cell implantation necropsies were performed. Counting of peritoneal metastatic nodules revealed the number of nodules of control group. (14.2 +/- 6.7) > i.v. group (5.3 +/- 4.1) > i.p. group (0.41 +/- 0.7) (p < 0.05). Weight of omental tumors showed Control group (0.246 +/- 0.136 g) > i.v. group (0.140 +/- 0.068 g) > i.p. group (0.051 +/- 0.017 g) (i.v.-i.p., p < 0.01). The mouse body weight decrease less in the i.p. group than in the i.v. group (p < 0.05) throughout this experiment. The results of this experiment demonstrated intraperitoneal sequential MTX/5-FU therapy was more effective than intravenous sequential MTX/5-FU therapy for potential peritoneal seeding and peritoneal micrometastases from the gastric cancer. Moreover, the side effect of intraperitoneal administration was milder than by the intravenous route.

Adenocarcinoma↗

Acetabular labral tears: contrast-enhanced MR imaging under continuous leg traction.

OBJECTIVE: The objective of this study was to evaluate the effects of continuous leg traction on contrast-enhanced MR imaging of the hip joint and to determine whether MR imaging under these conditions is useful for demonstrating acetabular labral tears. DESIGN AND PATIENTS: Nineteen hips underwent MR imaging with a T1-weighted spin-echo sequence, followed by MR imaging under continuous leg traction after intravenous injection of gadolinium-DTPA. Joint fluid enhancement and labral contour detection were evaluated. Eleven hips had labral tears shown by conventional arthrography, arthroscopy and macroscopic surgical findings. Assessment of labral tears by MR imaging was correlated with the diagnosis based on these standard techniques. RESULTS AND CONCLUSIONS: Joint fluid enhancement was obtained in all hips at 30 min after injection. Superior and inferior labral surfaces were completely delineated in 1 hip on the unenhanced MR images, and in 7 and 13 hips, respectively, on the enhanced images under traction. The enhanced images under traction depicted 9 of the 11 labral tears. Comparison between the unenhanced image and the enhanced image under traction avoided mistaking undercutting of the labrum for a tear in 4 hips. Contrast-enhanced MR imaging under traction was valuable for detecting labral tears non-invasively and without radiation. Follow-up examinations using this method in patients with acetabular dysplasia can help to clarify the natural course of labral disorders and enable better treatment planning.

Acetabulum↗

Inducible osteonecrosis in a rabbit serum sickness model: deposition of immune complexes in bone marrow.

We established inducible osteonecrosis in a rabbit serum sickness model. Osteonecrosis with marrow necrosis could be induced by the intravenous injection of horse serum in two doses separated in time by a period of three weeks. In this model, osteonecrosis could be successfully produced in rabbit femoral metaphysis. The incidence of marrow necrosis was 45% (9 of 20 rabbits) and trabecular necrosis occurred in 6 of 20 rabbits (30%) at 7 days after the second injection of the horse serum. In bone marrow of the femoral metaphysis, extravasation of erythrocytes and the formation of micro-thrombi in arterioles were often observed in an early stage of the present model and both findings correlate well each other (p = 0.0001). Immune complexes could be demonstrated using immunohistochemistry in bone marrow of the femoral metaphysis as well as in glomeruli of the kidney. Extravasation of erythrocytes in bone marrow of the femoral metaphysis was observed in 8 of 12 (67%) cases with immune complex deposition in the sinusoidal space of the femoral metaphysis and in 12 of 21 (57%) cases with immune complex deposition in glomeruli of the kidney. Immune complex deposition both in the sinusoidal space of femoral bone marrow (p = 0.0385) and in glomeruli of the kidney (p = 0.0209) closely related to extravasation of erythrocytes and microthrombi in arterioles in the early stage of this model. Early microcirculatory injury (extravasation of erythrocytes and microthrombi in arterioles) adjacent to osteonecrosis could be induced by immune complex deposition in femoral bone marrow and might be predictable characteristics for the inducible osteonecrosis in the present serum sickness model. The important findings in this study were that early microcirculatory injury was closely related to the deposition of immune complexes in femoral bone marrow, and that early microcirculatory injury associated with immune complex deposition was located close to osteonecrotic regions.

Animals↗

Bone scintigraphy as an indicator for dome osteotomy of the pelvis: comparison between scintigraphy, radiography and outcome in 57 hips.

We performed dome pelvic osteotomy in 57 hips (54 patients) because of acetabular dysplasia. All patients had preoperative scintigraphy and were followed for more than 2 years. Excellent or good results were obtained in 49 hips, but 8 hips deteriorated. All hips which deteriorated had preoperatively a spotty isotope uptake image localized to the weight bearing area and the medial area of the joint. No hip without this image deteriorated, even when preoperative radiography showed advanced arthrosis. Our findings indicate that bone scintigraphy may be a more reliable predictor of failure for this operation than radiography.

Adolescent↗

MRI of early osteonecrosis of the femoral head after transcervical fracture.

We have carried out a prospective study of 17 patients (14 women, 3 men) of mean age 48 years (21 to 76) with transcervical fractures of the femur using MRI to detect early evidence of avascular necrosis of the head. Two fractures were Garden stage I, 12 stage II, and three stage III. We performed internal fixation under radiological control at a mean of five days (2 to 15) after injury using a titanium cannulated cancellous screw or a titanium compression hip screw. MRI was performed at one, six and 12 months and then yearly after operation. T1- and T2-weighted images were obtained by a spin-echo technique. The duration of follow-up of patients who did not subsequently require replacement of the head of the femur was from 2 to 5 years (mean 3.2). One month after operation eight of the 17 hips showed a band of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images indicating lesions in the femoral head away from the fracture line. These were of three types: type I was a small infarct at the superolateral region of the femoral head and was seen in three hips; type II was a shallow lesion from the superolateral region to the fovea of the femoral head (three hips); and type III was a large lesion occupying most of the femoral head (two hips). No further changes were seen in the MRI after six months from operation. Collapse of the femoral head did not occur in the three hips with type-I lesions, but two of the three type-II hips and both type-III hips subsequently collapsed. At the final follow-up the three hips with a type-I lesion and one with a type-II were still asymptomatic but radiography showed sclerosis in the femoral head corresponding to the MRI lesions. The nine hips which showed no changes on MRI at one month had no abnormal findings on physical examination, radiography or MRI at final follow-up.

Adult↗

Enhancement of DNA repair activity in rat-liver cells exposed to cisplatin.

Rat-liver cells (Ac2F cells) were transfected with cisplatin-damaged eucaryotic expression vectors carrying luciferase cDNA (cis-DDP-pVJ3luc) and incubated. The lysate of the incubated cells was subjected to a luciferase activity assay. Graded decrease in the activity was observed with increasing levels of platination of the plasmid DNA. In another experiment, Ac2F cells were pre-incubated in the presence of cisplatin ranging in concentration from 0.5 to 3 mu M. The viable cells were transfected with cis-DDP-pVJ3luc and incubated in the absence of this drug. The lysate of the incubated cells was subjected to the same assay. The level of the luciferase activity was raised with increasing cisplatin concentration. These results suggest that the repair activity for cis-DDP-pVJ3luc DNA is enhanced in Ac2F cells exposed to cisplatin.

Animals↗

Binding affinities of highly repetitive DNA components for a nuclear scaffold protein from rat-ascites hepatoma cells.

Separate samples of a self-ligated tandem dimer of a highly repetitive DNA component (369-bp HindIII fragment) from rat-ascites hepatoma nuclei were digested with different restriction enzymes that cleave only once in the monomer. The resulting 369-bp sequence-permuted monomers showed anomalously slow gel electrophoretic mobility. Of them, the XmnI fragment had the slowest mobility. This suggests that bending of the helix axis is the strongest in this fragment. Our previous work has shown that such a repetitive bent DNA has selective affinities for two nuclear scaffold proteins from rat liver that have molecular weights of 123,000 and 130,000 Hibino et al. (1992) Biochem. Biophys. Res. Commun., 184, 853-858; Hibino et al. (1993) Biochim. Biophys. Acta, 1174, 162-170). In the present experiment, it has been found that the nuclear scaffold fraction from rat-ascites hepatoma cells does not contain these proteins, but does have a repetitive bent DNA-binding protein that has a molecular weight of about 230,000. These results imply that there is some difference in the structure of nuclear DNA attachment region between rat liver and the hepatoma.

Animals↗

The immune reaction to heterologous serum causes osteonecrosis in rabbits.

Osteonecrosis (ON) was produced experimentally in rabbits by intravenous injection of horse serum. Eighty adult rabbits were used: 16 were injected twice with isotonic saline (Group A), 24 were injected once with saline and once with horse serum (Group B), and 40 were injected twice with horse serum (Group C). Both femurs of each rabbit were obtained from 2 h to 7 weeks after the final injection an were subjected to histological examination. No pathological changes were seen in Groups A and B. In Group C, 5 of 15 rabbits (33%) showed ON (necrosis of trabecula and bone marrow) in the femoral metaphysis. In Group C, the early major pathological findings in bone marrow are extravasation of erythrocytes in sinusoidal spaces and microthrombi in small arteries and arterioles near the lesion of extravasation. Immune complexes were demonstrated in the kidney within 24 h of the final injection of horse serum. The present study suggests that immunological reaction associated with serum sickness may play an important role in inducible ON and this model will contribute toward clarifying the pathogenesis of ON.

Animals↗

Cisplatin-modified DNA-binding proteins in a nuclear extract of rat-liver cells.

A mobility shift DNA-binding assay showed that cisplatin-modified DNA-binding proteins are present in the nuclear extract of rat-liver cells (Ac2F cells). The major binding proteins of 22.5, 23, 96.5 and 112 kDa were identified in vitro. The binding activity of the 23 kDa protein was markedly enhanced in the cells that were cultured in the presence of cisplatin, and was inhibited by addition of cycloheximide to the culture. Our previous work [Hibino et al. (1994) Biochem. Biophys. Res. Commun. 202, 749-756] has shown that an Mg(2+)-dependent endo-exonuclease activity endogenous to Ac2F-cell nuclei is enhanced in the presence of cisplatin. Thus, the results of the present study imply that specific binding of the nuclear proteins to cisplatin-DNA lesions in rat-liver cells is involved in the mechanism of enhancement of this nuclease activity.

Animals↗

[Complications in the intraperitoneal chemotherapy with the implantable intraperitoneal port and the strategy for the prevention of the complication].

Fifty-four patients with gastrointestinal carcinomas were treated with intraperitoneal chemotherapy through devices, and an implantable port system which had been used subcutaneously. The complications of the implantable ports were analysed in this study. There were 1 bowel perforation, 2 cases of retention of ascites, 2 infections, 2 inflow obstructions and 8 cases of pain, especially in the perineal or lower abdominal area. The number of patients requiring removal of the device due to complications were 7; 1 perforation, 2 ascites, 2 infections and 2 for pain. The strategy for reducing the complications due to the device were analysed as follows. A soft catheter should be selected. The catheter in the abdominal cavity should not be long, not as long as the tip of catheter touch the bottom of pelvic organs. Due care for kinking of the catheter should be taken in the implanting procedure. Antibiotics should be applied in and around the port. Steroids should be added to the solution for intraperitoneal chemotherapy.

Aged↗

[Intraperitoneal infusion therapy of MTX and 5-FU for advanced gastric cancer and its peritoneal metastasis].

We administered methotrexate (MTX) and 5-fluorouracil (5-FU) into the peritoneal cavity as chemotherapy after operation for advanced gastric cancer from a port implanted subcutaneously during the operation, every or every other week. It has been said that MTX tends to be kept in the peritoneal cavity, so the kinetics of MTX is important when it was administered there in. We investigated the concentrations of MTX in the peritoneal cavity and serum with infusion into the peritoneal cavity (IP), and compared it with intraarterial (IA) and intravenous (IV) administration. The results were the lower serum concentration of MTX in IP than in both IA and IV at 1-2 hours after infusion, but thereafter it was the same level in each group. The intraperitoneal concentration of MTX was lower than the detectable level at 24-48 hours after infusion. On the other hand, we investigated the side effects of this therapy, and only one of 20 cases given therapy many times had nausea and vomiting. So the intraperitoneal infusion therapy of MTX and 5-FU seemed to be safe.

Adult↗

Polyethylene sockets and alumina ceramic heads in cemented total hip arthroplasty. A ten-year study.

From 1981 to 1983, we implanted Bioceram type-4 and type-5 prostheses in 61 hips in 54 patients with osteoarthritis secondary to acetabular dysplasia, congenital subluxation, or congenital dislocation of the hip. Fifty-seven hips in 50 patients were followed for a mean of 11.1 years (10 to 13). The mean age of the patients at operation was 53 years (31 to 70). Functional evaluation using the Merle d'Aubigné and Postel hip score showed a 77% success rate. Radiological loosening occurred in three femoral (5%) and 16 acetabular components (28%). Autologous femoral head grafts were used in 18 hips and became incorporated, giving mechanical support to the socket except for one which occupied a large weight-bearing area and eventually collapsed. The mean polyethylene wear was 1.1 mm (0 to 3.6) and the mean wear rate was 0.10 mm/year (0 to 0.31). A high rate of wear correlated with calcar resorption (p > 0.002) but not with acetabular loosening. There was no breakage of a ceramic head. Study of the ceramic heads and polyethylene sockets retrieved after ten years showed excellent surface roughness, sphericity, and bending strength for the heads but scratches and voids were seen on the sockets.

Bone Cements↗

Bipolar cup design may lead to osteolysis around the uncemented femoral component.

Thirty-eight patients with a total of 45 primary uncemented bipolar hemiarthroplasties with smooth femoral components were observed for an average period of 5 years. Clinical results were excellent in 17, good in 15, fair in 10, and poor in 3 hips. Radiographs showed stem loosening and bipolar head migration in 12 and 2 hips, respectively. Endocortical femoral osteolysis developed in 26 hips (58%). Eight hips required revision surgery. All the revised hips showed circumferential wear of the polyethylene insert rims without substantial wear of the bearing surface. Histologic examination of the fibrous membrane around the stem showed many polyethylene particles that had been phagocytized by macrophages or surrounded by foreign body giant cells. No metal particles were observed at this site. The intrinsic functional mechanism of the bipolar endoprosthesis leads to persistent cyclic impingement of the stem neck on the rim of the bipolar head, producing polyethylene particles and frequent stem loosening by periprosthetic osteolysis. Unless this structural problem can be corrected and the durability of the prosthesis increased, the bipolar system should not be used for hemiarthroplastic surgery.

Adult↗