Biomedical subjects

N Sugano

Publications and source records attributed to N Sugano.

At least 73 records · Page 4Linked to original sources

PubMed1998

Involvement of DNA methylation in binding of a highly repetitive DNA component to nuclear scaffold proteins from rat liver.

Experimental reduction of the amount of CpG methylation in a highly repetitive DNA component was achieved by growth of Ac2F cells in the presence of 5-aza-2'-deoxycytidine or procainamide, as judged by the results of methyl-sensitive restriction endonuclease digestion and colony hybridization. Modification of genomic DNA with these DNA methylation inhibitors increased the release of 370-bp highly repetitive DNA from rat chromosomal DNA by HindIII digestion. This result indicated that highly repetitive DNA components in the nuclear scaffold fraction are hypermethylated. On the other hand, methylated DNA was used for southwestern analysis to investigate the protein(s) which bind specifically to the DNA in the nuclear scaffold fraction. The introduction of additional methylated cytosines within a highly repetitive DNA component affected the binding of DNA to the nuclear scaffold proteins. Thus, cytosine methylation may be involved in the regulation of gene expression and construction of the higher-order structure of chromatin.

Animals↗

PubMed1998

Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation.

Cigarette smoke is a major risk factor for lung cancer and respiratory infections. This increased susceptibility may result from cigarette smoke-induced impairment of the immune system. In this study, we evaluated the effect of nicotine on the production of inflammatory mediators by activated macrophages. Pretreatment with nicotine caused a significant inhibition of LPS-induced IL-1, IL-8, and PGE2 expression at the transcriptional level in U937 cells. Nicotine inhibited the activation of a transcription factor, NF-kappaB, which in turn, binds to and mediates transcriptional activation of these genes. These inhibitory effects of nicotine may contribute to cigarette smoke-induced immunosuppression.

Cyclooxygenase 2↗

PubMed1998

Involvement of phosphorylation in binding of nuclear scaffold proteins from rat liver to a highly repetitive DNA component.

The results of our previous work [Hibino et al., Biochim. Biophys. Acta 1174 (1993) 162-170] suggested that a highly repetitive DNA component facilitates bending of the helix axis to be recognized by the nuclear scaffold proteins from rat liver, P123 and P130. In the present experiment, it was shown that binding of these proteins to such a repetitive DNA component from rat liver nuclei (370-bp XmnI fragment) is based on a cooperative mode of interaction, although the binding activity of P130 is much higher than that of P123. The immunoblot analysis with anti-phosphoamino acid antibodies suggested that phosphorylation of serine and threonine residues occurs on P123 and P130, but also of tyrosine residue(s) on P130. The phosphatase assay showed that phosphoryl groups on these proteins may be involved in altering the DNA binding activities of the proteins. Thus, the results in the present study imply that phosphorylation of a nuclear scaffold protein in addition to the degree of bending of the DNA helix axis plays an important role in anchoring chromatin to the nuclear scaffold and in construction of a higher-order chromatin structure.

Animals↗

PubMed1998

Computed-tomography-based computer preoperative planning for total hip arthroplasty.

For precise preoperative planning in total hip arthroplasty (THA), we developed a technique of computed tomography (CT)-based computer preoperative planning and compared this technique with the single X-ray and template method generally used. The subjects of this study were 42 hips in 38 patients who underwent THA using a cementless total hip system. Preoperatively, a standard anteroposterior X-ray of the hip was taken, and conventional preoperative planning was done with a template of the total hip system. Transverse images were obtained using a helical CT scanner, and a CT-based computer preoperative plan was performed on true coronal slice images of the proximal femur reconstructed from CT data. Postoperatively, 29 hips (69%) showed good proximal fit of the femoral component to the medial endosteal line. Of the 20 hips with good proximal fit on preoperative X-ray planning, 12 hips had good proximal fit on postoperative X rays. Sensitivity and specificity of the proximal fit on X-ray templating were 41 and 23%, respectively. In 27 of 28 hips with good proximal fit on reconstructed CT images preoperatively, the postoperative X ray revealed good proximal fit. Sensitivity and specificity of the proximal fit on computer planning were 93 and 86%, respectively. Twelve hips with good proximal fit on preoperative templating, the reconstructed images, and the postoperative X ray had 20 degrees or less of combined femoral neck anteversion and external rotational contracture of the hip on the X-ray table. Eight hips with good proximal fit on preoperative templating and proximal poor fit on the reconstructed images had 17-65 degrees of combined version and rotational contracture. In 16 hips with poor proximal fit on preoperative templating and good proximal fit on the reconstructed images, the combined version and rotational contracture ranged from 17 to 69 degrees. When combined femoral neck anteversion and external rotational contracture of the hip is less than 15 degrees, the simple X-ray and template method might be sufficient for THA planning. Otherwise, the CT-based method of preoperative planning is recommended.

Arthroplasty, Replacement, Hip↗

PubMed1998

Articular cartilage evaluation in osteoarthritis of the hip with MR imaging under continuous leg traction.

We conducted MR evaluations of acetabular and femoral cartilages in 27 hips of patients with osteoarthritis and 10 hips of normal volunteers by a fat-suppressed three-dimensional (3D) pulse sequence using a continuous leg traction method, and correlated the results with radiographic assessment. Normal condition of the acetabular and femoral cartilages was clearly demonstrated in the normal volunteers. Grading of abnormalities was possible for each cartilage in the patients with osteoarthritis. In early osteoarthritis graded by radiography, a high prevalence of abnormalities was detected in the acetabular cartilage as compared with the femoral cartilage. Despite the structural difficulty in evaluation of the hip joint cartilage, our MR imaging technique can provide information concerning a wide spectrum of cartilage abnormalities even in the identical radiographic stage, which will lead to improvement in the evaluation of disease progression and in surgical planning.

Adult↗

PubMed1998

Cyclosporin A inhibits collagenase gene expression via AP-1 and JNK suppression in human gingival fibroblasts.

A frequent side effect of cyclosporin A (CsA) administration is gingival overgrowth. Although the molecular mechanisms of CsA-induced gingival overgrowth are still unknown, it has been postulated that CsA acts on lipopolysaccharide (LPS) to induce fibroblastic activity, which results in an increase of the extracellular matrix. Here we provide evidence that CsA is able to affect signal transduction of LPS-induced collagenase expression in fibroblasts. Treatment of fibroblasts with LPS caused activation of collagenase gene, activator protein-1 (AP-1) and c-Jun N-terminal kinase (JNK). These activations were blocked by CsA. We suggest that inhibitory effects of CsA on LPS-induced signal transduction may contribute to the mechanism of CsA-induced gingival overgrowth.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1998

The Metal-Cancellous Cementless Lübeck total hip arthroplasty. Five-to-nine-year results.

We implanted 51 Metal-Cancellous Cementless Lübeck (MCCL) prostheses into 45 patients with dysplastic hips and followed 49 hips (96.1%) for five to nine years. One had needed revision for stem fracture and one for infection; the clinical outcome of the other 47 hips was assessed using the Merle d'Aubigné and Postel hip score. All hips were either excellent (63%) or good (37%). Three patients (6%) had mild thigh pain at six months, but this had settled within two years. Serial radiographs showed stable fixation with bone ingrowth in all hips, with increased density of the cancellous bone in contact with the implant and some trabecular ingrowth. There was early varus shift of the stem in one hip, but this stabilised in three months. Osteolysis of the femoral cortex was seen in one hip at seven years after surgery, and mild bone resorption due to stress shielding in 31 (63%). Acetabular bone grafting with autogenous bone from the femoral head gave successful support to the socket in 13 hips. The MCCL prosthesis gave satisfactory mid-term results in patients with osteoarthritis secondary to hip dysplasia.

Acetabulum↗

PubMed1998

The morphology of the femur in developmental dysplasia of the hip.

We studied the morphometry of 35 femora from 31 female patients with developmental dysplasia of the hip (DDH) and another 15 from 15 age- and sex-matched control patients using CT and three-dimensional computer reconstruction models. According to the classification of Crowe et al 15 of the dysplastic hips were graded as class I (less than 50% subluxation), ten as class I/III (50% to 100% subluxation) and ten as class IV (more than 100% subluxation). The femora with DDH had 10 to 14 degrees more anteversion than the control group independent of the degree of subluxation of the hip. In even the most mildly dysplastic joints, the femur had a smaller and more anteverted canal than the normal control. With increased subluxation, additional abnormalities were observed in the size and position of the femoral head. Femora from dislocated joints had a short, anteverted neck associated with a smaller, narrower, and straighter canal than femora of classes I and II/III or the normal control group. We suggest that when total hip replacement is performed in the patient with DDH, the femoral prosthesis should be chosen on the basis of the severity of the subluxation and the degree of anteversion of each individual femur.

Adult↗

PubMed1998

MRI evaluation of steroid- or alcohol-related osteonecrosis of the femoral condyle.

We reviewed 30 patients (46 knees) with steroid- or alcohol-related osteonecrosis of the femoral condyle. Their average age was 35 (14-61) years and the mean observation time was 7 (3-16) years. The medio-lateral extent and the anterior-posterior (AP) location of the necrotic lesion were evaluated on T1-weighted MRI and related to the collapse of the condyle. The size of the lesion was classified into three categories on the mid-coronal MRI of the femoral condyle: there were 44 small, 20 medium, and 9 large lesions. The condyle was divided into 3 zones: anterior, middle, and posterior. The location of the lesion was evaluated on the mid-sagittal image. There were 7 anterior, 9 middle, 29 posterior, 14 middle and posterior and, in 14 cases, all 3 zones were involved. 44 small lesions did not collapse, while 6/20 medium lesions and 5/9 large lesions collapsed. No lesion involving only one zone collapsed, while 4/14 lesions involving the middle and posterior zones and 7/14 lesions involving all three zones progressed to collapse. 4/6 condyles with large necrotic lesions involving all three zones collapsed. We conclude that the extent of the necrotic lesion on both the mid-coronal and mid-sagittal planes is of importance for the prognosis of osteonecrosis of the femoral condyle.

Adolescent↗

PubMed1998

[Preoperative chemotherapy for advanced colorectal carcinomas--comparison of histological effect between UFT + leucovorin tablet and UFT alone].

The authors analyzed the histological effect of preoperative chemotherapy for 41 colorectal advanced cancer patients using resected specimens. Twenty patients in the UFT + LV group received 400 mg/day of UFT and 30 mg/day of leucovorin for 10-14 days just before the operations. Twenty-one patients with UFT alone received UFT 400 mg/day during the same period. Only one patient in the UFT + LV group developed the side effect of mild leukocytopenia. The histological effect of the UFT + LV group was superior to that of the UFT alone group (p = 0.03). The number of Grade 1a and 1b in the UFT + LV group was 14 (60.9%) and 7 (30.4%), while in the UFT group 16 (66.7%) and 2 (8.3%). Histological examination revealed no lesions which showed Grade 2 and 3 in both groups. There was the tendency for the histological effect in moderately differentiated adenocarcinomas to be superior to that in well-differentiated adenocarcinomas in both group. The histological effect in metastatic lymph nodes was superior to that in the original colorectal lesions in both groups. This suggests preoperative chemotherapy with UFT + LV and UFT could achieve the clinical down-staging of advanced colorectal cancer.

Administration, Oral↗

PubMed1998

[Pharmaco-dynamic influence under ascites or laparotomy on intraperitoneal sequential MTX/5-FU therapy].

We studied pharmaco-dynamic changes of intraperitoneal sequential MTX (30 mg)/5-FU (750 mg) therapy in gastric cancer patients with malignant ascites and those who had undergone a gastrectomy. The serum and ascites levels of MTX in patients with malignant ascites decreased much slower than in patients without ascites. In patients with ascites, the serum MTX concentration peaked 8 hours later and then gradually decreased. The ascites MTX level decreased as low as 1/10 2 days after the intraperitoneal administration. The serum and ascites 5-FU levels revealed a minor prolongation of 5-FU concentration in patients with ascites. Gastrectomy did not affect the pharmaco-dynamics of MTX in post-operative patients with sequential intraperitoneal administration of MTX/5-FU on 1, 8 and 15 POD.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[The Osaka concept. "Dome osteotomy" with of without labrum resection].

Acetabular dysplasia represents the most common aetiology for secondary osteoarthritis of the hip joint in Japan. On radiographs progress of the disease can be classified in four stages (I to IV). Labral lesions are common accompanying findings in acetabular dysplasia, representing an important prognostic factor. Therefore we routinely use conventional arthrography to classify labral lesions in three types (normal, torn and detached). From 1978 to 1983 a modified Chiari osteotomy of the pelvis (dome osteotomy) was performed in 64 hip joints without arthrotomy. The preoperative radiography showed labral lesions in 66%. After an average follow-up of 4 years, 43 of the 44 patients with a normal or torn labrum showed excellent or good results. On contrast, 50% of the 20 patients with a detached labrum showed fair and poor results only. From 1984 to 1989 an arthrotomy was combined with dome osteotomy in 29 hip joints and labral lesions had to be resected in 16 cases. The results were generally good in patients with arthrosis grade I and II, but in stage III they were only fair. Thus, the success of labral surgery can only be achieved in early stages of dysplasia. Based on our findings dome osteotomy combined with arthrotomy and labral surgery can be recommended in patients with labral lesions and hip dysplasia grade I and II.

Acetabulum↗

PubMed1997

Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction.

Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter. Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection.

Aspirin↗

PubMed1997

Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients.

Fifty-one renal allograft recipients (15-62 years old, mean: 37 years) were monitored for 2.5-6.5 years (average: 4.3 years) after surgery by using magnetic resonance imaging (MRI) to find (i) initial signs of osteonecrosis of the femoral head (ONF), (ii) the presence of bone marrow edema as an initial sign of ONF, (iii) any changes of MRI patterns, and (iv) the relationship between these MRI findings and prognosis. MRI was performed preoperatively (baseline), and whenever possible during the 6-9th week, 12-16th week, 12th month, and yearly thereafter. T1- and T2-weighted images were obtained by using a spin echo technique. Abnormalities were first detected on MRI of 23 femoral heads in 13 patients between 6 weeks and 12 months. All lesions first showed a low intensity band on T1-weighted images and a high intensity band on T2-weighted images. No symptoms or diffuse patterns, such as bone marrow edema, preceded the appearance of the band pattern. After the 12th month, no new abnormal findings on MRI were detected. The lesions were classified into Type A, B, or C, according to the location. 12 of the 16 Type C femoral head lesions, which extend beyond the medial two thirds of the weight-bearing portion of the acetabulum, became symptomatic 7-14 months after transplantation and then progressed to collapse. Bone marrow edema appeared with radiological collapse and symptoms. With the exception of five lesions in three patients who failed to be MR imaged until 12 months postoperatively, all lesions were first detected on MRI within 16 weeks after transplantation. We therefore postulate that the ischemic event that causes ONF will have occurred within 12 weeks after transplantation, considering the time lag of reparative reaction to the dead bone.

Adolescent↗

PubMed1997

Purification and characterization of a DNA binding protein in a nuclear scaffold fraction from rat ascites hepatoma cells.

Our most recent work [Hibino et al. (1995) Cancer Lett., 88, 49-55] has shown that the selective binding affinities of highly repetitive DNA components for a nuclear scaffold protein from rat ascites hepatoma cells (P230) depend on the degree of sequence-directed bending of the helix axis. In the present experiment, this protein has been highly purified and isolated by a series of column chromatographic procedures to migrate as a single band to a molecular weight position of 230 kd on a SDS-polyacrylamide gel. A filter binding assay showed that the binding of a repetitive AT-rich component (369 bp XmnI fragment) from the hepatoma nucleus, which has a strongly bent overall structure, to isolated P230 is based on a cooperative mode of interaction. Distamycin A, which binds specifically to AT-rich DNA, removed the bend in the XmnI fragment and inhibited binding to this protein. These results suggest that AT-rich regions in highly repetitive DNA cause bending of the helix axis to be recognized by nuclear scaffold protein(s). Moreover, it has been shown that the nuclear scaffold fraction from rat liver or an actively growing hepatocyte cell line (Ac2F cells) does not contain P230, but does have a repetitive bent DNA binding protein (P130), which has an apparent molecular weight of 130 kd. In addition, the immunoblot analysis showed that mouse anti-P130 antiserum reacts with P230. Thus, the results in the present study imply that there is some difference in the higher order structure of the nuclear DNA attachment region between rat liver or actively growing hepatocytes and the hepatoma, although P230 appears to be immunochemically similar to P130.

Animals↗

PubMed1997

Longitudinal evaluation of time related bone remodeling after cementless total hip arthroplasty.

Bone remodeling after cementless total hip arthroplasty was evaluated by dual energy x-ray absorptiometry in a longitudinal study of 32 hips. After insertion of a fully porous surface anatomic stem made of cobalt chromium, bone mineral density was analyzed until at least 2 years postoperatively. Bone remodeling was evaluated in terms of regional bone density changes in the seven adjacent periprosthetic zones as well as the global change in bone density distribution over the entire periprosthetic area. At 12 months after the operation, the averaged regional bone mineral density in all seven zones showed a rapid decrease, ranging from 9% to 24% of the bone mineral density present at 2 weeks postoperatively. Thereafter, the bone density change appeared to be stabilized. The global change in the bone density distribution was expressed as two summarizing statistical indexes derived from principal component analysis: the first index represents the change of average bone mineral density over the entire periprosthetic area, and the second represents the severity of bone mineral density decrease in the proximal area versus the distal area. The second index proved that more bone density reduction occurred in the proximal area, but this was variable among patients and correlated significantly with the stem size and the initial bone mineral density in the distal part of the periprosthetic area. This longitudinal dual energy x-ray absorptiometry study suggests that a large part of the bone remodeling after cementless hip arthroplasty ceases within 1 year postoperatively, and stem size and the initial bone density around the distal portion are important considerations for predicting the proximal bone density decrease during the early rapid remodeling period.

Absorptiometry, Photon↗

PubMed1997

[Morphology and origin of micronuclei induced by mitotic inhibitors].

In order to elucidate the morphological variation and the origin of erythrocytic micronuclei induced by mitotic inhibitors, each of clastogens (mitomycin C and cyclophosphamide) and spindle poisons (vincristine and colchicine) was administered intraperitoneally into a rat. After 24 h, the bone marrow smear was prepared and subjected to the microscopic analysis. In consequence, the sizes of micronuclei (MNSs) induced by spindle poisons were generally larger than those (MNCs) induced by clastogens. On the other hand, the bone marrow cells containing micronucleated erythrocytes were fractionated by cellulose column chromatography and then Percoll-gradient centrifugation. The micronuclear DNA was extracted from the resulting erythrocyte fraction and subjected to the dot blot hybridization with a centromeric or telomeric DNA probe. This experiment showed that centromeric and/or telomeric DNAs are enriched more in MNSs than in MNCs. Thus, such hybridization techniques and the morphological analysis would be available for classifying micronucleus-inducing drugs.

Animals↗

PubMed1997

Early deterioration after modified rotational acetabular osteotomy for the dysplastic hip.

We performed a modified, rotational acetabular osteotomy through a lateral transtrochanteric approach on 19 hips in 18 patients with a dysplastic joint. Six hips in six patients were operated on using the original approach. The mean age at operation was 28 years (14 to 54) and the mean period of follow-up 2.3 years (1 to 4.4). Clinical evaluation using the Merle d'Aubigne score showed excellent or good results in 76%. Radiologically, 15 hips showed good acetabular remodelling and no signs of progressive osteoarthritis. In ten hips (40%) there was chondrolysis and collapse of the transferred acetabulum or both within one year, although this gave only mild pain in some patients. Factors which were significantly associated with the grade of outcome included age at the time of operation, the thickness of the transferred acetabulum, failure to use a bone graft, and a transtrochanteric approach.

Acetabulum↗