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Biomedical subjects

G Inoue

Publications and source records attributed to G Inoue.

At least 55 records · Page 3Linked to original sources
PubMed1997

Management of trans-scaphoid perilunate dislocations. Herbert screw fixation, ligamentous repair and early wrist mobilization.

A retrospective review of 28 patients with 29 trans-scaphoid perilunate dislocations who underwent open reduction and Herbert screw fixation is presented. The majority of the patients had satisfactory results at 24 months of follow-up. A significantly better range of wrist motion was obtained in postoperative patients treated with cast immobilization for 4 weeks compared with those treated for longer than 5 weeks. The scaphoid fractures united well, with proper alignment of the carpal bones, regardless of the length of cast immobilization. We recommend open reduction, internal scaphoid fixation using a Herbert screw, carpal ligament repair and early cast removal in the management of trans-scaphoid perilunate dislocations.

Adolescent↗
PubMed1997

Antihyperglycemic mechanism of M16209, an antidiabetic agent, in 3T3-L1 adipocytes.

We investigated the effect of M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) on glucose transport and the insulin signaling system in mouse-derived 3T3-L1 adipocytes. When M16209 (30 and 100 microM) was added to 3T3-L1 adipocytes and preincubated for 24 hours, the uptake of 2-deoxy-D-[3H]-glucose (2-DG) after insulin stimulation was enhanced. This effect was seen when preincubation with M16209 was performed in the presence of 6 and 20 ng/ml insulin, but M16209 did not increase the response to 600 ng/ml insulin. M16209 (100 microM) did not interfere with (125)I-insulin binding or with tyrosine phosphorylation of the insulin receptor beta-subunit and IRS-1. M16209 (100 microM) also had no effect on the level of glucose transporter (GLUT1 and GLUT4) protein, but it promoted the translocation of intracellular GLUT4 to the plasma membrane. In contrast, M16209 had no effect on the translocation of GLUT1. In summary, M16209 enhanced 2-DG uptake by 3T3-L1 adipocytes. Insulin binding to its receptor, autophosphorylation of the insulin receptor beta-subunit, and tyrosine phosphorylation of IRS-1 were unaffected by M16209. However, translocation of GLUT4 from the intracellular pool to the plasma membrane was facilitated.

3T3 Cells↗
PubMed1997

Management of acute perilunate dislocations without fracture of the scaphoid.

A retrospective review of 14 cases of acute perilunate dislocations without fracture of the scaphoid managed by three different forms of treatment was conducted at an average follow-up of 29 months. Treatment included closed or open reduction with cast immobilization only (n=2), closed reduction followed by percutaneous K-wire fixation of the carpus (n=4), and open reduction with repair of the torn scapholunate ligaments and K-wire fixation of the carpus (n=8). Based on Cooney's clinical scoring system, there were five excellent, five good, two fair and two poor results. The patients without ligamentous repair did as well as those with ligamentous repair when the scaphoid was reduced anatomically and stabilized with K-wires. In the latter, however, the scapholounate relationship was maintained more consistently. We believe that open reduction through a dorsal approach, direct repair of the scapholunate ligaments, and K-wire fixation of the carpus is a reliable method for obtaining satisfactory clinical and radiographic results in the management of acute perilunate dislocations without fracture of the scaphoid.

Acute Disease↗
PubMed1997

Avulsion fracture of the metacarpophalangeal joint of the finger.

Six patients with avulsion fractures of the metacarpophalangeal joints of the fingers are reported. Operation was performed in all cases. Judging from the operative findings, the radiological assessment of fragment shape is helpful in treatment. Surgery is recommended when the fragment is triangular or rectangular in shape because the fracture involves the articular surface. Conservative treatment is effective if the fragment is round because the articular surface of the joint is not involved in this type of fracture. The avulsed fragment often overlaps the metacarpal head and a collateral ligament injury is likely to be misdiagnosed. It is important to suspect this injury and assess the shape of the whole fragment for a good functional result.

Adolescent↗
PubMed1997

Repeat screw stabilization with bone grafting after a failed Herbert screw fixation for acute scaphoid fractures and nonunions.

Eight patients with persistent nonunions after failure of a Herbert screw fixation for both acute scaphoid fractures and nonunions underwent repeat screw internal fixation and bone grafting. They were followed for at least 1 year (average, 19 months) after their last surgical procedure. In 6 patients, union was achieved following the second surgery. These patients were pain free and resumed their previous occupations. The average range of wrist mobility was 87% of that of the uninvolved wrist, and grip strength averaged 93% of that of the uninvolved wrist. In 1 of the 2 patients with an unsuccessful outcome after the second procedure, union was achieved after a third procedure was performed that involved an inlay bone graft and internal fixation using a Kirschner wire. The remaining patient had relief of pain following denervation of the wrist joint. These 2 patients did not show marked clinical improvement and required a change of employment of light work. On the basis of study findings, it appears that revision with a repeat Herbert screw fixation and bone grafting is the treatment of choice for patients with persistent scaphoid nonunions following an unsuccessful Herbert screw procedure in which the screw is not correctly placed.

Acute Disease↗
PubMed1997

Herbert screw fixation by limited access for acute fractures of the scaphoid.

We describe a semi-closed method of Herbert screw fixation for acute fractures of the scaphoid. All 40 patients treated achieved solid union with satisfactory wrist function. This technique gave a significantly shorter time to union and allowed an earlier return to manual labour compared with conservative treatment. There were no complications. Semi-closed insertion requires considerable skill, but produces consistently satisfactory results after minimal exposure of the scaphoid.

Acute Disease↗
PubMed1997

Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin.

Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. But the same dose of wortmannin did not affect the formation of guanosine 5'-triphosphate (GTP)-bound Ras stimulated by either ligand. In KB cells, results similar to those in 3T3-L1 adipocytes were obtained. In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist.

3T3 Cells↗
PubMed1997

Ununited proximal pole scaphoid fractures. Treatment with a Herbert screw in 16 cases followed for 0.5-8 years.

We treated 16 cases of delayed union and nonunion of proximal one-third scaphoid fractures with cancellous bone grafting and retrograde insertion of a Herbert screw through a dorsal approach. Definite radiographic union was obtained in 13 of 16 patients after a median of 2 (0.5-8) years of follow-up. Using Cooney's clinical scoring system, 5 cases were excellent, 5 good, 5 fair and 1 poor. The treatment of ununited proximal pole scaphoid fractures with retrograde insertion of the Herbert screw offers the advantages of a short period of immobilization and a good function.

Adolescent↗
PubMed1997

[Geriatrics in the new program for initial postgraduate medical training in Japan].

Until 1993, initial postgraduate medical training in Japan was conducted only at university hospitals or other teaching hospitals. In 1994, the number of types of training sites was expanded to include health centers, nursing homes, and extended care facilities, which gave trainees chances to understand primary medical care in various settings, providing in-home as well as other non-hospital medical services. Since the new program seemed to increase training opportunities in geriatric medicine, questionnaires regarding the new program were sent by mail to all teaching hospitals in Japan (261); 213 responded. The results showed that 29 hospitals already had a program of care for the aged. The teaching sections were mainly internal medicine, psychiatry and rehabilitation medicine. Fifty hospital had plans to include care for the aged in their program in the near future. The number of programs that includes training in care for the aged is gradually increasing. It is hoped that during their initial postgraduate training many young doctors will come to recognize the importance of geriatric medicine.

Education, Medical, Graduate↗
PubMed1997

Herbert screw fixation for scaphoid nonunions. An analysis of factors influencing outcome.

A retrospective review of 160 cases of scaphoid nonunion treated by internal fixation using a Herbert screw with bone grafting was conducted at an average followup of 24 months. Definite radiographic union was achieved in 90% of cases. Based on Cooney's clinical scoring system, 80 cases had an excellent result, 37 had a good result, 33 had a fair result, and 10 had a poor result. Failure of union was related to the existence of avascular changes of the proximal fragment, instability of the fracture fragment, the prolonged delay in surgery, and the location of the fracture site. In the united scaphoids, the lengthy period of postoperative immobilization, the existence of osteoarthritis, and the prolonged delay in surgery were significant factors in the patient's functional outcome. Overall, the results do not support the view that a residual flexion deformity of the scaphoid is less likely to yield a satisfactory outcome, although it seems worthwhile to correct excessive angulation at the time of repair to promote an anatomic union, thereby preventing early arthritis. A bone graft with internal fixation using a Herbert screw and a shorter period of immobilization may give a satisfactory functional result when the nonunion is treated before the onset of arthritic changes in the wrist.

Adolescent↗
PubMed1996

Different pathways of postreceptor desensitization following chronic insulin treatment and in cells overexpressing constitutively active insulin receptors.

We have reported previously that substitution of the transmembrane domain of the insulin receptor with that of the erbB-2 oncogene (IRerbV-->E) results in constitutive activation of the insulin receptor kinase. Compared to NIH3T3 cells overexpressing wild-type insulin receptors (IRwt), cells overexpressing IRerbV-->E displayed a decrease in IRS-1 protein content by 55%, but basal tyrosine phosphorylation of IRS-1 was increased. This resulted in an increased association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, increased phosphatidylinositol 3-kinase activity in anti-IRS-1 immunoprecipitates, constitutive activation of p70 S6 protein kinase, and an increased association of Grb2 with Shc in the absence of ligand. However, Grb2 association with IRS-1 could not be detected in the basal or insulin-stimulated states, and mitogen-activated protein kinase (MAPK) activity could not be stimulated by insulin, epidermal growth factor, or platelet-derived growth factor. In contrast to IRerbV-->E, the insulin receptor content and its tyrosine phosphorylation were significantly decreased in IRwt cells chronically stimulated (>24 h) with insulin. With decreased IRS-1 content, tyrosine phosphorylation of IRS-1 was decreased by over 75%, leading to decreased IRS-1-associated PI 3-kinase and Grb2. In addition, Grb2 association with Shc and activation of MAPK and the p70 S6 kinase were insensitive to insulin stimulation. By contrast, association of Grb2 with Shc and activation of MAPK, but not the p70 S6 kinase, could be stimulated by epidermal growth factor or platelet-derived growth factor. These data suggest that there are multiple levels of postreceptor desensitization to insulin action. These are used somewhat differently in these two different models, probably due in part to the difference in receptor down-regulation.

3T3 Cells↗
PubMed1996

A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies.

Insulin receptor substrates-1 (IRS-1) is the major cytoplasmic substrate of the insulin and IGF-1 receptors. Recent studies have identified multiple sequence variants of IRS-1, especially in patients with non-insulin-dependent diabetes mellitus. In the present study, we have examined insulin-stimulated processes in 32D(IR) cells, a myeloid progenitor cell stably overexpressing the insulin receptor, transfected with wild-type human-IRS-1 or the most common human variant of IRS-1 in which glycine 972 is replaced by arginine. As compared to wild-type IRS-1, insulin stimulation of cells transfected with mutant IRS-1 exhibited a 32% decrease in incorporation of [3H]thymidine into DNA (P = 0.002), a 36% decrease in IRS-1 associated phosphatidylinositol (PI) 3-kinase activity (P = 0.004) and a 25% decrease in binding of the p85 regulatory subunit of PI 3-kinase to IRS-1 (P = 0.002). There was also a tendency for a decrease in Grb2 binding to IRS-1 and insulin-stimulated mitogen-activated protein kinase activity, however, these were not statistically significant. The changes occurred with no change in insulin receptor or IRS-1 tyrosine phosphorylation. These data indicate that the mutation in codon 972 in IRS-1 impairs insulin-stimulated signaling, especially along the PI 3-kinase pathway, and may contribute to insulin resistance in normal and diabetic populations.

Arginine↗
PubMed1996

Amelioration of insulin resistance in genetically obese rodents by M16209, a new antidiabetic agent.

Improvement of metabolic disorders by M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin), an antidiabetic agent, was studied in genetically obese Zucker fa/fa rats and C57BL/6J ob/ob mice. In fa/fa rats oral administration of M16209 (30 and 100 mg/kg/day) for 7 days dose dependently improved hyperinsulinemia without affecting body weight. Oral glucose loading (2 g glucose/kg body weight) after 10 days of administration to fa/fa rats revealed that M16209 significantly improved glucose tolerance both 30 and 60 min after glucose loading, but did not affect preload serum glucose levels. At one day after 13 days of administration of M16209, the serum levels of triglyceride, total cholesterol and free fatty acid were clearly lower in treated fa/fa rats than those in untreated rats. In C57BL/6J ob/ob mice, M16209 given for 28 days at doses of 30 and 100 mg/kg/day improved hyperinsulinemia, hyperglycemia and hypercholesterolemia without affecting body weight. In a hyperinsulinemic euglycemic clamp study in fa/fa rats, administration of M16209 for 7 days at a dose of 100 mg/kg/day significantly normalized the decreased metabolic clearance rate but did not show any effect on the augmented hepatic glucose output. These findings demonstrate that improvement of metabolic disorders in genetically obese rodents by M16209 is due to amelioration of insulin resistance in peripheral tissues.

Administration, Oral↗
PubMed1996

Insulin-induced activation of phosphoinositide 3-kinase in Fao cells.

Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85 alpha). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4-6% of the total PI3-kinase, and their specific activity was 11-14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200-C215 region.

Animals↗
PubMed1996

The natural history of scaphoid non-union. Radiographical and clinical analysis in 102 cases.

A retrospective radiographic and clinical analysis of 102 symptomatic patients with 104 scaphoid nonunions of at least 1 year's duration was conducted. Osteoarthritis occurred in 22% of non-unions of less than 5 years' duration, 75% of those of 5 to 9 years' duration, and 100% of those of 10 years' duration or more. An all-over incidence of osteoarthritis in the wrist was 55%. Osteoarthritic changes occurred initially at the scaphoid-radial styloid joint which were manifested by radial styloid pointing and/or dorsal radioscaphoid osteophyte formation, later progressing to the midcarpal joint. Osteoarthritis at the scaphoid-radial styloid joint was significantly associated with dorsiflexed intercalated segment instability (DISI) deformity. An overall incidence of DISI deformity of the wrist was 56%, and the frequency of DISI pattern increased with longer duration of non-union. There was an increased incidence of avascular necrosis of the proximal fragment with time, especially after 20 years. There was no correlation between symptoms of pain and the severity of arthritis or the duration of non-union, but a good correlation between the duration of non-union and reduced grip strength or decreased wrist motion. A symptomatic non-union of the scaphoid is significantly likely to progress to osteoarthritis according to a predictable sequence, becoming worse both radiographically and clinically with time.

Adolescent↗
PubMed1996

Amyloidosis localized in the sigmoid colon.

A 79-year-old woman was admitted to our hospital presenting with bloody stool. Colonoscopic examination showed many irregularly-shaped discrete ulcerations in the sigmoid colon extending for a length of 6 cm, situated 16 cm proximal to the anal ring. Histopathology of the biopsy specimen in and around the ulcerations revealed the deposition of amyloid materials in the proper mucosa and the submucosa. Similar ulcerations were not detected by endoscopy in other parts of the gastrointestinal tract, i.e., esophagus, stomach, and duodenum. Multiple biopsy specimens taken from various parts of the gastrointestinal tract other than the sigmoid colon showed no amyloid deposition. Further investigations showed no particular abnormality in any organs and the patient was free of such systemic disease as myeloma or collagen disease. The findings were consistent with those of localized sigmoid amyloidosis. Localized colonic amyloidosis is rare, this being the fifth patient reported in Japan in the past 15 years.

Aged↗
PubMed1996

Constrictive paralysis of the posterior interosseous nerve without external compression.

Four cases of constrictive neuropathy of the posterior interosseous nerve (PIN) in the absence of external compression are reported. All patients presented with a history of severe elbow pain with no apparent cause, followed by paralysis of the PIN. There were one or two well-localized constrictions on the PIN proximal to the arcade of Frohse where no obvious external compressive structure was observed. After epineurotomy with or without neurorrhaphy, three patients had a complete return of motor function within 1 year. The remaining patient required tendon transfer after resection of the abnormal segment of nerve.

Adolescent↗