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Biomedical subjects

S Mitani

Publications and source records attributed to S Mitani.

At least 37 records · Page 2Linked to original sources

Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes.

We previously isolated RBP56 cDNA by PCR using mixed primers designed from the conserved sequences of the RNA binding domain of FUS/TLS and EWS proteins. RBP56 protein turned out to be hTAFII68 which was isolated as a TATA-binding protein associated factor (TAF) from a sub-population of TFIID complexes (Bertolotti A., Lutz, Y., Heard, D.J., Chambon, P., Tora, L., 1996. hTAFII68, a novel RNA/ssDNA-binding protein with homology to the proto-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. EMBO J. 15, 5022-5031). The RBP56/hTAFII68, FUS/TLS and EWS proteins comprise a sub-family of RNA binding proteins, which consist of an N-terminal Ser, Gly, Gln and Tyr-rich region, an RNA binding domain, a Cys2/Cys2 zinc finger motif and a C-terminal RGG-containing region. Rearrangement of the FUS/TLS gene and the EWS gene has been found in several types of malignant tumors, and the resultant fusion proteins play an important role in the pathogenesis of these tumors. In the present study, we determined the genomic structure of the RBP56/hTAFII68 gene. The RBP56/hTAFII68 gene spans about 37kb and consists of 16 exons from 33bp to 562bp. The longest exon, exon 15, encodes the C-terminal region containing 19 repeats of a degenerate DR(S)GG(G)YGG sequence. While the structure of the FUS/TLS gene has been reported previously, we determined the total DNA sequence of the FUS/TLS gene, consisting of 12kb. The RBP56/hTAFII68, FUS/TLS and EWS genes consist of similar numbers of exons. Comparison of the structures of these three genes showed that the organization of exons in the central part encoding a homologous RNA binding domain and a cysteine finger motif is highly conserved, and other exon boundaries are also located at similar sites, indicating that these three genes most likely originate from the same ancestor gene.

Base Sequence↗

Treatment outcome of osteofibrous dysplasia.

The disease course of six tibial lesions in five patients with osteofibrous dysplasia who were followed longer than 10 years (average: 16.8 years) was analyzed retrospectively. Three patients had a lesion of the unilateral tibia; one patient had lesions of the unilateral tibia and fibula; and one patient had lesions of the bilateral tibiae and ulnae. Curettage and autogeneic bone graft were performed on two lesions, which then healed. Of four lesions on which curettage and xenogeneic bone grafts were performed, three lesions healed, and one developed local recurrence. Curettage and xenogeneic bone graft were performed on the recurrent lesion, which finally healed and the deformity stopped. Three lesions healed without surgical treatment. During the long-term follow-up, this disease showed a clear tendency of healing. Surgical treatment should be considered in patients with disease uncontrollable by conservative treatment or those who have a high possibility of impending fracture and progressing deformity.

Adolescent↗

Surgical management of hip dislocation in children with arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita (AMC) is a rare disease with multiple joint contractures. It is widely believed that bilaterally dislocated hips should not be reduced since movement is satisfactory and open reduction has had poor results. Since 1977 we have performed a new method of open reduction using an extensive anterolateral approach on ten hips in five children with AMC. The mean age at surgery was 31.5 months (17 to 64) and the mean follow-up was 11.8 years (3.8 to 19.5). At the final follow-up all children walked without crutches or canes. Two managed independently, one required a long leg brace and two had short leg braces because of knee and/or foot problems. The clinical results were good in eight hips and fair in two and on the Severin classification seven hips were rated as good (group I or group II). We recommend the extensive anterolateral approach for unilateral or bilateral dislocation of the hip in children with arthrogryposis or developmental dislocation of the hip.

Acetabulum↗

Inhalation of interleukin-2 combined with subcutaneous administration of interferon for the treatment of pulmonary metastases from renal cell carcinoma.

BACKGROUND: Interleukin-2 is the most promising antitumor agent for advanced renal cell carcinoma, but systemic immunotherapy with interleukin-2 might be limited because of inadequate efficacy and severe adverse effects. In this study, we treated 7 patients with lung metastases from renal cell carcinoma with topical application of interleukin-2 by inhalation. METHODS: Patients received 100,000 IU of interleukin-2 by inhalation 4 times a day and 9,000,000 IU of interferon-alfa-2a subcutaneously for 5 consecutive days per week. They also received, by oral administration, 800 mg of cimetidine and 50 mg of indomethacin per day. After informed consent was obtained, the treatment started and the absence of any intolerable adverse effects was confirmed in a hospital. Then the treatment continued in an outpatient clinic for at least 3 months. RESULTS: Of 6 assessable patients, 5 responded to this treatment; 2 patients developed a partial response (33%) and 3 remained stable (67%). Disease progressed in the remaining patient. Therapy was discontinued in 1 patient because of his poor general condition. No severe adverse effects were observed, but pulmonary fibrosis probably associated with this treatment occurred in 1 patient. CONCLUSION: Although more cases and further evaluation are necessary to assess the significance and the safety of the inhalation of interleukin-2, this treatment is anticipated to be an option for selected patients with lung metastases from renal cell carcinoma.

Administration, Inhalation↗

Treatment of developmental dislocation of the hip in children after walking age. Indications from two-directional arthrography.

We treated 120 children between the ages of 12 and 31 months with 137 developmental dislocations of the hip and reviewed them at a mean follow-up of 14 years. We had used two-directional arthrography of all hips before reduction to evaluate the anterior, superior, and posterior portions of the limbus. Of the 137 hips, 64 had no interposed limbus in the AP view of the arthrogram, but 45 of these had an interposed anterior or posterior portion of the limbus. The hips with good stability and no interposed limbus in either AP or lateral arthrograms had excellent results by closed methods; in the other cases the results were less satisfactory. Our findings suggest that hips suitable for management by closed reduction can be identified by two-directional arthrography. Hips shown to have an interposed limbus are best managed by open reduction.

Age Distribution↗

Deformity of the proximal end of the femur following open reduction for developmental dislocation of the hip.

We studied deformity of the proximal end of the femur following open reduction using the wide exposure method for developmental dislocation of the hip. We reviewed radiographs of 22 children with unilateral dislocation of the hip who had undergone open reduction between one and three years of age. Ages at final examination ranged from 14 to 21 years. None of the patients in this study had undergone any additional surgery. Avascular necrosis of the femoral head was not observed in any patients. Radiographic measurements were observed when the children were 3, 6, 9, and 12 years old, and at the final examination. Coxa magna and valga were the factors associated with poor results. Coxa valga had occurred at 6 to 12 years of age, but rapidly improved thereafter. Throughout the course of treatment the epiphysis-femoral neck angle was within the normal range. The fusion of the epiphyseal growth plates on both sides occurred simultaneously. The coxa valga was due to valgus of the femoral neck, and not to valgus head tilt. These results suggest that, provided the mechanics of the joint have been properly corrected as in our operation, the biomechanics of the hip will improve until growth ceases, but that it may take more than ten years to attain normality.

Adolescent↗

Long-term results of Charnley low-friction arthroplasty for coxarthrosis with congenital hip dysplasia. 15 year follow-up study.

We studied more than fifteen-years' follow-up results of cases treated with low-friction arthroplasty (LFA) for coxarthrosis with congenital hip dysplasia. Thirty-four LFAs in 32 patients (2 males and 30 females) were followed up for an average of 18.8 years (range: 15 to 23.3 years). The mean age at surgery was 53 years (range: 36 to 67 years). In three patients, 4 hips needed revision surgery due to loosening of the prostheses. At the final follow up, using Hodgkinson's criteria, type 0 demarcation of the socket appeared in 9 cases, type 1 in 5 cases, type 2 in 4 cases, type 3 in 4 cases, and type 4 in 12 cases. According to Harris' criteria, there was no sign of loosening of the stem in 16 cases, however there was a possibility of loosening in 8 cases, probability in 2 cases, and definite loosening in 8 cases. The survival rate with socket loosening as the end point was 76.5% at the 10 year follow-up, 67.6% at 15-years' follow-up, and 50.9% at 20-years' follow-up. The survival rate with stem loosening as the end point was 82.4% at 10-years' follow-up, 79.4% at 15-years' follow-up, and 63.8% at 20-years' follow-up. The survival rate with prostheses loosening either socket or stem as the end point was 64.7% at 10-years' follow-up, 55.9% at 15-years' follow-up, and 34.6% at 20-years' follow-up. The survival rate with revision surgery as the end point was 100% at 10-years' follow-up, 94% at 15-years' follow-up, and 85.1% at 20-years' follow-up.

Adult↗

MB fraction of cumulative creatine kinase correlates with insulin secretion in patients with acute myocardial infarction: insulin as a possible determinant of myocardial MB creatine kinase.

To test whether insulin is a regulatory factor of myocardial MB creatine kinase content, we investigated the correlation between the ability of insulin secretion and the MB fraction of cumulative CK released in patients with acute myocardial infarction. We analyzed 18 patients who underwent successful direct angioplasty within 10 hours of the onset of their first myocardial infarction. Exclusion criteria were age more than 75 years, heart failure, severe obesity, multivessel disease, and history of diabetes mellitus. Cumulative activity of serum MB CK divided by that of total CK was defined as MB%, which was considered to represent myocardial MB CK content. Two weeks or more after the onset of myocardial infarction, 75 gm oral glucose tolerance test with serial determination of plasma glucose and serum insulin (0, 0.5, 1, 2, 3 hours) was done. Urinary and plasma catecholamines and echocardiographic left ventricular (LV) mass were measured. MB% significantly correlated with insulinogenic index (r = 0.564, p = 0.019), insulin area (r = 0.594, p = 0.012), insulin area/glucose area (r = 0.630, p = 0.007), and urinary adrenaline (r = -0.542, p = 0.025) and tended to correlate with plasma adrenaline (r = -0.431, p = 0.084). Age, body mass index, infarct size, glucose metabolism, and LV mass were not significant univariate predictors of MB%. Multivariate analysis showed that the ability of insulin secretion contributed to MB% more than catecholamines did and that insulin area/glucose area was the strongest independent predictor of MB% (t = 3.01, p = 0.015). Thus MB fraction of cumulative CK released, indicative of Myocardial MB CK distribution, strongly related to the ability of insulin secretion in subjects without overt insulin resistance. Regulation by insulin of myocardial MB CK is suggested.

Adrenergic Agonists↗

Enalapril improves heart failure induced by monocrotaline without reducing pulmonary hypertension in rats: roles of preserved myocardial creatine kinase and lactate dehydrogenase isoenzymes.

We investigated the redistribution of myocardial isoenzymes of creatine kinase (CK) and lactate dehydrogenase (LD) in rats with right heart failure induced by monocrotaline and assessed the effect of enalapril, an angiotensin converting enzyme inhibitor. Wistar rats were divided into four groups: (1) control (n = 20), (2) control + enalapril (25 mg/kg/day) (n = 22), (3) monocrotaline (50 mg/kg) (n = 45), (4) monocrotaline (50 mg/kg) + enalapril (25 mg/kg/day) (n = 32). After 4 weeks, the monocrotaline group developed severe pulmonary hypertension and right ventricular hypertrophy with marked decrease in myocardial norepinephrine and increase in both plasma atrial natriuretic peptide and mortality rate (33.3%). The marked decrease in both MM and mitochondrial CK ('creatine shuttle') and the relatively constant BB and MB CK caused the net depression of total CK. The depression of LD1 (aerobic LD) was remarkable compared with the relatively constant total LD. In the monocrotaline+enalapril group, mortality rate (9.4%), cardiac hypertrophy and plasma atrial natriuretic peptide were all significantly reduced and myocardial norepinephrine recovered although pulmonary hypertension was not improved at all. However, myocardial total, MM and mitochondrial CK and LD1 activities were all recovered completely or partially in this group. Thus, enalapril reduced cardiac hypertrophy and failure and improved the prognosis in this model of pulmonary hypertension. This beneficial effect of enalapril was not associated with pulmonary vasodepression but with the inhibition of myocardial isoenzyme redistribution of CK and LD, i.e. the preservation of 'creatine shuttle' and aerobic LD.

Animals↗

Pulmonary nodules in patients with a history of radical nephrectomy for renal cell carcinoma.

BACKGROUND: Nine patients with a history of radical nephrectomy for renal cell carcinoma underwent surgical removal of newly detected pulmonary nodules at the Hiroshima University Hospital. Six patients had metastatic lung tumors two patients had bronchogenic primary carcinomas and one had a granulomatous infection. METHODS: To determine if any characteristics can distinguish a new primary carcinoma from metastatic renal cell carcinoma, we reviewed the nine patients described above. The patients with pulmonary metastases and those with new primary lung cancers did not differ in age, sex, history of smoking, clinical stage and pathological findings of the renal primary site, on the location and size of the pulmonary nodules. RESULTS: Only the interval between the nephrectomy and the appearance of the new pulmonary lesion may be a predictive factor. This interval was 48 and 51 months for the patients with new primary lung cancers but varied from 0 to 39 months for the patients with metastatic renal cell carcinoma. A solitary nodule had an equal chance of being metastatic or primary. CONCLUSIONS: These results indicate that a solitary nodule that is detected at a longer interval after radical nephrectomy may be a new primary lung cancer. Once new pulmonary nodules are identified in a patient with a history of radical nephrectomy for renal cell carcinoma, surgical excision is required for a final diagnosis before initiating therapy for metastases.

Adult↗

Neural parvalbumin and calretinin in the tooth pulp.

Parvalbumin- and calretinin-immunoreactivities (CR-irs) were examined in the molar tooth pulp of the rat using immunohistochemical methods. CR-ir fibers were further classified based on the tachykinin-ir revealed by a double immunofluorescence method. The rat root pulp contained three types of nerve fibers; parvalbumin-ir smooth fibers, CR-ir (TK-negative) smooth fibers and CR-ir (TK-ir) varicose fibers. These fibers projected toward the roof of the pulp chamber and pulp horn without marked ramification. In the subodontoblastic layer at the roof of the pulp chamber and pulp horn, parvalbumin-ir smooth fibers repeatedly ramified and extended varicose terminals into the odontoblastic layer. CR-ir (TK-negative) smooth fibers reached the subodontoblastic layer without marked ramification and gave rise to varicose terminals that appeared to terminate within the subodontoblastic layer. On the other hand, CR-ir (TK-ir) varicose fibers proceeded to the subodontoblastic layer at the roof of the pulp chamber and pulp horn, where they ramified and penetrated the odontoblastic layer. The present study indicates that the rat tooth pulp contains myelinated parvalbumin-ir and CR-ir (TK-negative) fibers, and unmyelinated CR-ir (TK-ir) fibers, and that they project varicose terminals to the subodontoblastic and odontoblastic layers. The central projection sites of these sensory fibers have yet to be revealed.

Animals↗

Changes in c-fos induction in dorsal horn neurons by hindpaw formalin stimulation following tibial neurotomy.

The hindpaw was partially denervated by the tibial nerve transection in adult rats. At post-transection intervals varying from 2 to 168 days, the hindpaw was stimulated bilaterally by subcutaneous injection of formalin. The excitability of dorsal horn neurons was expressed as the percentage ratio of the number of formalin-induced c-fos protein-like immunoreactive neurons (fos-neurons) on the neurotomized (experimental) side to that on the un-neurotomized (control) side. At 2 days post-injury, a marked reduction in the number of fos-neurons was noted in laminae I-VII of the lumbar spinal cord. Among these, reduction was greatest in the medial 3/8 of laminae I and II (terminal field of the tibial nerve, i.e. tibial territory), and smallest in the lateral 5/8 of the same laminae (the peroneal/hip territory). The low level of c-fos induction remained unchanged for 7 days. At 14 days, the excitability of neurons in all laminae showed a marked increase compared to the post-injury days 2 and 3 combined. Thereafter, the increased level of excitability in the tibial territory was maintained throughout the post-injury period examined in this study. On the other hand, a statistically significant increase in excitability in the peroneal/hip territory was only seen between 14 and 28 days and the excitability almost returned to the baseline (days 2 and 3 post-transection combined) level at 42 days. Although deeper laminae (III-VII) contained much less formalin-induced fos-neurons, they also exhibited post-injury excitability changes with a temporal pattern similar to that of the peroneal/hip territory of laminae I and II.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Metastatic renal cell carcinoma arising in a native kidney of a renal transplant recipient.

We report a case of metastatic renal cell carcinoma arising in the native kidney of a renal transplant recipient. A 39-year-old man, who had undergone living renal transplantation from his mother at age 32, presented with complaints of paraplegia of the leg caused by a pathological fracture of the 3rd lumbar vertebra. The bone tumor was extirpated and pathological examination revealed metastatic adenocarcinoma. Abdominal computerized tomography showed a tumor in the right native kidney. Right nephrectomy and resection of the right 7th rib tumor were performed. Pathological evaluation demonstrated renal cell carcinoma of the right native kidney (pT2bpN0pV0M1, mixed cell type, grade 2). Postoperatively, cyclosporine was discontinued and natural interferon-alpha was given. The remaining bone metastasis had completely resolved with no significant sign of rejection 1 year after surgery.

Adult↗

Determination of the tooth mobility change during the orthodontic tooth movement studied by means of Periotest and MIMD (the mechanical impedance measuring device for the periodontal tissue).

Two mechanical devices were selected to attempt to assess any changes in tooth mobility when orthodontic force was applied. A Periotest (PT) for assessing mobility and a mechanical impedance measuring device (MIMD) were the instruments chosen to diagnose the changes in the periodontal condition. The relative mobility of four canines after orthodontic tooth movement manipulation was assessed over a 4-week period. Both devices were able to detect very small changes in tooth mobility and could follow the changes during tooth movement. According to the Periotest unit, the tooth mobility changes were not within the clinically abnormal range, despite the initial retraction load from a sectional arch, applied in a horizontal direction with about 150 gm for each tooth. In all instances, the contiguous maxillary first premolar had been removed 1 to 2 months before force application. The tooth mobility observed in this investigation could be different from that caused by periodontal disease or traumatic injury. Just after orthodontic tooth movement manipulation, the Periotest values (PTV), as measured on the Periotest, of tooth mobility decreased and the resistance as measured by the mechanical impedance measuring device (MIMDM) was increased. Thus, initially, there is a greater resistance to movement with decreased mobility. After the experimental period of 4 weeks, there was an increase in the mobility, as measured by the Periotest and the mechanical resistance decrements were observed. However, the Periotest units showed some different changes occasionally that did not seem to reflect the state of tooth movement. This needs to be investigated further over a longer period of time. On the basis of the results obtained, it does appear that it is feasible to use these devices to determine mobility changes in patients at various stages of orthodontic treatment.

Cuspid↗

Rearrangement of bcl-2 is detectable in Hodgkin's disease by polymerase chain reaction.

The authors examined the occurrence of the t(14;18) chromosomal translocation in 44 cases of Hodgkin's disease (HD) using the polymerase chain reaction and Southern blot hybridization with non-radioactive oligonucleotide probes. DNAs were extracted from unfixed, fresh-frozen and formalin-fixed, paraffin-embedded biopsy specimens. Southern blot hybridization of the amplification product showed that, of 44 HD DNAs, three had a detectable t(14;18) breakpoint at the mbr (major breakpoint region), while none had a detectable t(14;18) breakpoint at the mcr (minor cluster region). Of the three cases positive for a t(14;18) breakpoint at the mbr, two were of lymphocyte predominance type, and the other was of mixed cellularity type.

Apoptosis↗

Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation.

We have sequenced 45 mutations in mec-7, a beta-tubulin gene required for the production of 15-protofilament microtubules in the nematode Caenorhabditis elegans, and have correlated sequence alterations with mutant phenotypes. The expression patterns of most alleles have also been determined by in situ hybridization and immunocytochemistry. Most (12/16) complete loss-of-function alleles, which are recessive, result from nonsense mutations, insertions, or deletions; three others disrupt a putative GTP-binding domain. Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers. Most (8/9) mild alleles are caused by missense mutations. Two mild alleles appear to increase microtubule stability and lead to the elaboration of ectopic neuronal processes in mec-7-expressing cells. Most (15/23) mutations that cause severe dominant or semidominant phenotypes are clustered into three discrete domains; four others occur in putative GTP-binding regions. Many of these dominant mutations appear to completely disrupt microtubule assembly.

Alleles↗

[Surgical treatment of renal cell carcinoma with extension into the vena cava].

Between 1985 and 1992, 9 patients (6 men and 3 women), 50-76 years old (mean age 63.6), underwent radical nephrectomy and removal of the tumor thrombus for the treatment of renal cell carcinoma extending into the vena cava at the Department of Urology, Hiroshima University Hospital. Seven tumors were located in the right kidney and two in the left kidney. Three tumor thrombi extended into the vena cava within 2 cm (level 1 according to the Novick's classification), 2 extended into the infrahepatic vena cava (level 2), 2 extended into the suprahepatic vena cava (level 3), and other 2 extended into the right atrium (level 4). Two patients had distant metastases preoperatively. The tumor thrombi at the level 1 were removed by venacavotomy with a short duration of surgery and a small amount of blood loss, while in those at the level of 2 or 3, both the duration of surgery and the amount of blood loss increased because the mobilization of the liver needed to remove the thrombi. For removing tumor thrombi at the level 4, cardiopulmonary bypass and deep hypothermic circulatory arrest were applied, resulting in longer duration of surgery but less amounts of blood loss than those at the level 2 or 3. Postoperatively, 2 patients had a renal insufficiency and another 2 had a liver dysfunction. One operative death occurred in this series because of pulmonary embolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of Helicobacter pylori infection in the pathogenesis of gastritis.

We conducted a prospective study to evaluate the relationship between H. pylori infection and gastritis in a Japanese population. The study population consisted of 92 patients with endoscopically proven gastritis. Biopsy specimens were taken from the gastric mucosa from the corpus and antrum according to the Sydney system for the new classification of gastritis. H. pylori was histologically found in 84.3% of patients for mononuclear (MN) cell infiltration and in 88.1% of those positive for polymorphonuclear (PMN) cells. H. pylori was not found in any of nine patients without MN cell infiltration (P < 0.001), while 68.8% of patients without PMN cell infiltration were positive for H. pylori (P < 0.03). The frequency of MN cell infiltration in H. pylori-positive patients was significantly higher than that in H. pylori-negative patients (100% vs 65.4%; P < 0.001). The frequency of PMN cell infiltration in H. pylori-positive patients was also significantly higher than that in H. pylori-negative patients (54.5% vs 23.1%; P < 0.01). The incidence of MN cell infiltration in the antrum was significantly higher than that in the gastric corpus in H. pylori-positive gastritis patients (93.2% vs 65.1%; P < 0.001). The incidence of PMN cell infiltration was also higher in the antrum than in the corpus in H. pylori-positive gastritis patients, although the difference was not significant (42.0% vs 31.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric Mucosa↗