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Biomedical subjects

G Inoue

Publications and source records attributed to G Inoue.

At least 73 records · Page 4Linked to original sources

Dislocation of the extensor tendons over the metacarpophalangeal joints.

Twenty-seven patients who had received treatment for dislocation of the extensor tendons over the metacarpophalangeal joint were reviewed. Sixteen patients had traumatic dislocations, seven had spontaneous dislocations, and four had congenital dislocations. The long finger was most frequently affected. The other fingers were affected almost equally. Displacement of the extensor tendon always occurred in the ulnar direction in the long and ring fingers. The index and little fingers exhibited different patterns of dislocation: two patients had ulnar dislocation of both the common and proprius tendons, and the remaining five patients had divergent dislocation of the two tendons. Nonsurgical treatment was undertaken in six cases. Surgery was performed in 21 cases. No recurrent dislocations were reported in any of the patients. Based on our experience, patients seen within 2 weeks of injury initially should be treated with splinting of the involved metacarpophalangeal joint. Chronic dislocations should be treated with a primary repair of the defect in the sagittal band. When the sagittal band is absent or deficient, the tendon must be stabilized using a loop procedure with a tendon slip.

Adolescent↗

One-stage repair of skin and tendon digital defects using the arterialized venous flap with palmaris longus tendon: an additional four cases.

The use of the arterialized venous flap with a palmaris longus tendon transfer has previously been reported. Further trials of this technique were conducted in four patients to reconstruct complicated finger injuries involving loss of skin and extensor tendon. In contrast to the results of previous cases, those of recent cases are more encouraging. This technique may be the procedure of choice in patients with digital skin defects, where there are associated extensor tendon defects with exposed bone.

Adult↗

Surgical repair of traumatic medial disruption of the elbow in competitive athletes.

Five active athletes with acute medial elbow rupture were treated with muscle-ligamentous repair and a spiked washer. All patients regained full strength as well as stability of the elbow, and resumed previous sporting activities within 3 months of surgery. Early surgical repair of the ligament and flexor mass should be considered for active athletes who exhibit gross instability of the elbow on a valgus stress test without anaesthesia.

Adolescent↗

A novel substrate for insulin-sensitive serine/threonine kinase in intact cells.

We have studied insulin-stimulated threonine phosphorylation of cellular proteins by immunoblotting and immunoprecipitation using antiphosphothreonine antibody (anti-P-Thr). A 50-kilodalton protein (p50) was found to be greatly phosphorylated on threonine residues upon insulin stimulation in intact rat hepatoma cells (Fao) and Chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR). Insulin induced threonine phosphorylation of this protein in a dose-dependent manner, with an ED50 of 3-6 x 10(-9) M. The 50-kilodalton phosphoprotein (pp50) was detectable 20 min after exposure of the cells to insulin, and phosphorylation reached a maximum after 90 min. Immunoprecipitation of pp50 with anti-P-Thr required extraction of the cellular proteins with sodium dodecyl sulfate and dithiothreitol, and subcellular fractionation of the cells revealed that pp50 is present in the membrane fraction, implying that pp50 is a protein integrated into the membrane component in the cells. Tryptic phosphopeptide mapping of the pp50 was distinct from that of the insulin receptor beta-subunit. Phosphoamino acid analysis of the pp50 demonstrated that insulin increased phosphorylation, mainly of threonine and moderately of serine, whereas pp50 did not contain phosphotyrosine. Cycloheximide, a protein synthesis inhibitor, did not affect the insulin-induced appearance of pp50 in the cells. pp50 was not detectable in A431 cells and KB cells stimulated by epidermal growth factor. These data suggest that p50 is a novel endogenous substrate for insulin-sensitive serine/threonine kinase in intact cells.

Animals↗

Camptodactyly resulting from paradoxical action of an anomalous lumbrical muscle.

A 17 year old girl presented with camptodactyly resulting from an anomalous insertion of the lumbrical muscle into the flexor digitorum superficialis tendon. The fourth anomalous lumbrical muscle paradoxically caused flexion of the proximal interphalangeal (PIP) joint of the little finger when the patient extended the fingers fully. She was operated on, and the lumbrical tendon was cut at its insertion into the flexor digitorum superficialis tendon. The tight fascial band and skin contracture at the PIP joint were released, and the skin defect covered with a transposed flap. She made a good recovery and eight months after operation had only 40 degrees residual flexion deformity with full flexion of the PIP joint of the little finger.

Adolescent↗

Anti-phosphoserine and anti-phosphothreonine antibodies modulate autophosphorylation of the insulin receptor but not EGF receptor.

We examined the effect of anti-phosphothreonine and anti-phosphoserine antibodies on insulin receptor autophosphorylation. These antibodies did not affect insulin binding activity of the receptor. These antibodies, however, inhibited insulin-stimulated autophosphorylation of insulin receptor, while did not affect EGF-stimulated autophosphorylation of EGF receptor. The inhibition was reversed by adding large amounts of phosphoserine or phosphothreonine. These data suggest that phosphoserine and phosphothreonine on insulin receptor play an important role in insulin-induced conformational change of the receptor.

Animals↗

Effects of ML-9 on insulin stimulation of glucose transport in 3T3-L1 adipocytes.

Treatment of 3T3-L1 adipocytes with insulin resulted in activation of 2-deoxyglucose transport activity and translocation of glucose transporters (GLUT4 and GLUT1) from the cytoplasmic space to the plasma membrane. ML-9 (a myosin light chain kinase inhibitor) inhibited insulin stimulation of 2-deoxyglucose transport activity by 80% at 100 microM (IC50 = 27 microM) without affecting 2-deoxyglucose transport activity in the basal state. The inhibition was independent of extracellular Ca2+ concentration and almost fully reversible at 40 microM ML-9. ML-9 did not inhibit insulin-stimulated tyrosine phosphorylation of 95-kDa protein in the wheat germ agglutinin-purified preparation and of 95- and 160-kDa proteins in intact cells. However, ML-9 inhibited insulin-induced translocation of both GLUT4 and GLUT1 in a dose-dependent manner. The dose-response curves were similar to those observed for the inhibition of insulin stimulation of 2-deoxyglucose transport activity. Neither insulin nor ML-9 affected the phosphorylation state of both heavy and light chains of myosin. Therefore, it seems likely that ML-9 inhibits the insulin-induced translocation of glucose transporters at a step beyond the insulin receptor kinase activity by a mechanism different from that affecting phosphorylation of the myosin light chain. Phosphorylating activity of microtubule-associated protein 2 and myelin basic protein was stimulated by insulin, and this stimulation was not affected by ML-9. ML-9, however, inhibited the phosphorylating activity in vitro and insulin stimulation of the phosphorylating activity of ribosomal protein S6 in intact cells in a dose-dependent manner similar to that observed for the inhibition of insulin stimulation of glucose transport. These results suggest that mitogen-activated protein kinase may be one of the constituents in intracellular insulin signaling to the glucose transport system.

3T3 Cells↗

Specific activity of phosphatidylinositol 3-kinase is increased by insulin stimulation.

We investigated whether phosphatidylinositol 3-kinase (PI3K) is phosphorylated and whether its specific activity is increased by insulin stimulation in vivo using Fao cells and antibodies raised against the 85 kDa subunit of PI3K, insulin-receptor substrate-1 (IRS-1), and phosphotyrosine (pTyr). PI3K activity was detected in the immunoprecipitate produced with anti-PI3K at a basal state. The activity was increased 2-3-fold by insulin stimulation, although the protein concentration of kinase in the anti-PI3K immunoprecipitates was the same before and after insulin stimulation. Both anti-pTyr and anti-IRS-1 antibodies immunoprecipitated the kinase activity only after insulin stimulation. After the first immunoprecipitation with anti-pTyr, the supernatant was immunoprecipitated once more with anti-PI3K. PI3K activity in the second immunoprecipitate revealed little difference between the basal and insulin-stimulated states, suggesting that most of the insulin-activated portion of PI3K was precipitated by anti-pTyr. Both IRS-1 and the insulin-receptor beta-subunit (95 kDa) were phosphorylated on tyrosine residues by insulin stimulation and immunoprecipitated with anti-pTyr. However, phosphorylation of neither subunit of PI3K (85 kDa or 110 kDa) was detectable in the immunoprecipitate produced with anti-pTyr. The 185 kDa pTyr-containing protein was immunoprecipitated with anti-PI3K after insulin stimulation, although there was little phosphorylation of the 85 kDa protein. pTyr in the 110 kDa protein immunoprecipitated with anti-PI3K was below detectable levels. These results indicate that the specific activity of PI3K is increased by insulin stimulation without detectable tyrosine phosphorylation of PI3K itself in Fao cells. The majority of the insulin-activated portion of PI3K is associated with pTyr-containing proteins including IRS-1, which suggests that this is important for activation of PI3K by insulin.

Animals↗

Preparation of anti-phosphoserine and anti-phosphothreonine antibodies and their application in the study of insulin- and EGF-induced phosphorylation.

We prepared antibodies against phosphoserine (P-Ser) and phosphothreonine (P-Thr) by immunizing rabbits with P-Ser or P-Thr conjugated to bovine serum albumin. The antibodies (anti-P-Ser and anti-P-Thr) were purified using P-Ser or P-Thr affinity columns. Anti-P-Thr was highly specific for P-Thr, while anti-P-Ser showed weak cross-reactivity with P-Thr. We showed that these antibodies can immunodetect serine/threonine phosphorylated insulin and epidermal growth factor (EGF) receptors and several proteins which are phosphorylated on serine/threonine residues in response to insulin or EGF stimulation. The antibodies will certainly provide a good tool for discovering novel kinases and substrates involved in signal transduction.

Animals↗

Osteosynthesis for longstanding nonunion of the lateral humeral condyle.

Six patients with symptomatic longstanding nonunion of the lateral humeral condyle were treated by internal fixation with iliac bone graft. The indication for surgery was pain and weakness in the elbow. Follow-up ranged from 18 months to 4 years, with an average of 28 months. Bony union was achieved in all cases. Stability and strength of the elbow were restored in all cases, but postoperative elbow motion was decreased in three patients, with an average loss of 6.7 degrees of the motion present before surgery. All patients were painfree in the elbow upon strenuous activities and satisfied with the outcome of the procedure.

Adolescent↗

Treatment of chronic dislocation or subluxation of the distal radioulnar joint.

Twenty-eight patients with chronic instability of the distal radioulnar (DRU) joint were treated with 4 procedures: Sauvé-Kapandji procedure (11 cases), Milch ulnar shortening osteotomy (9 cases), Bowers hemiresection interposition arthroplasty (4 cases), or ligamentous reconstruction (4 cases). The indication for operation in all cases was pain in the DRU joint and weakness of grip strength. Sixteen of 28 patients also complained of limitation of forearm rotation. At an average follow-up of 18 months, there were 72% satisfactory results in patients treated with the Sauvé-Kapandji procedure, 88.9% with the Milch procedure, 75% with the Bowers procedure, and no satisfactory results with ligamentous reconstruction. We believe that the Milch procedure is indicated for the wrist with mild instability with adequate articular surface of the DRU joint. The Bowers procedure and the Sauvé-Kapandji procedure are useful in treating patients with gross instability with or without articular damage to the DRU joint.

Adolescent↗

Arterialized venous flap for treating multiple skin defects of the hand.

An arterialized venous flap, with arterial blood flowing only through the vein of the flap, was used in each of five patients to cover multiple digital skin defects caused by trauma or burns. Four flaps survived completely, and one showed 30 percent partial necrosis. Although this procedure will require additional refinement, it permits a certain range of motion of the involved digits prior to flap division and inset.

Adult↗

Insulin resistance in Werner's syndrome.

Insulin resistance in Werner's syndrome (WS) was studied using the glucose clamp technique, and compared with physiologically aged and young subjects. Fasting immuno-reactive insulin (IRI) was increased in patients with Werner's syndrome compared with aged and young subjects. Metabolic clearance rate (MCR) of glucose was decreased in the aged and WS. A rightward shift of the dose-response curves of insulin and MCR of glucose was observed in the aged and WS with a more pronounced shift in the latter. MCR of insulin was also decreased in WS. [125I]insulin binding to erythrocytes was similar in the three groups. These results suggest that insulin resistance associated with WS is due to a post-binding defect manifested by a rightward shift of the dose-response curve of insulin-induced glucose disposal and a decrease in insulin clearance rate.

Adult↗

Monoclonal antibodies possibly recognize conformational changes in the human erythrocyte glucose transporter.

Two monoclonal antibodies (MAG17 and MAG20) were raised against the human erythrocyte glucose transporter, which was purified on an immunoaffinity column using a polyclonal antibody to the C-terminal peptide (residues 477-492) of the glucose transporter of HepG2 cells. To obtain antibodies which recognize the native glucose transporter integrated in the membrane, hybridomas were screened both by e.l.i.s.a. with purified glucose transporter and by dot-blotting with erythrocyte membranes. The antibodies immunoprecipitated D-glucose-inhibitable [3H]cytochalasin B-photoaffinity-labelled glucose transporters, but did not recognize the transporter on Western blotting. The presence of the C-terminal peptide did not inhibit the binding of these antibodies to the glucose transporter, suggesting that the antibodies recognized sites different from the transporter C-terminus. D-Glucose (0.1-100 microM) inhibited the binding of MAG17 and MAG20 to the transporter by 50%, indicating that the conformation of the epitopes was altered allosterically by D-glucose. Cytochalasin B inhibited the binding of MAG17 to the transporter, but enhanced the binding of MAG20 at low concentrations (less than 0.02 microM). These data suggest that the glucose transporter has high- and low-affinity binding sites for D-glucose and cytochalasin B, and that binding of D-glucose and cytochalasin B induces conformational changes in the transporter. Monoclonal antibodies which recognize the tertiary structure of the glucose transporter can be used for investigating its function and structure when integrated in the membrane.

Amino Acid Sequence↗

Radiolunate and radioscapholunate arthrodesis.

Eleven patients underwent radiocarpal arthrodesis for a wrist disease other than rheumatoid arthritis. Operations included seven radiolunate fusions and four radioscapholunate fusions. The indication for surgery was posttraumatic changes secondary to radius fracture (five), Kienböck's disease (three), localized arthritis secondary to sepsis (two) and acute comminuted fracture of the distal radius (one). All patients had arthritis or post-traumatic changes limited to the articulation between the radius and carpus. Follow-up ranged from 24 months to 7 years, with an average of 41 months. Postoperatively, average range of motion of the wrist was 30.9 degrees of extension, 22.7 degrees of flexion, 10 degrees of radial deviation, and 19.3 degrees of ulnar deviation, and grip strength averaged 81.8% of that for the uninvolved hand. Pain relief was achieved in all patients, and they were able to return to their previous occupation. Bony union was achieved in all cases. Degenerative changes in the midcarpal joint were not seen.

Adult↗