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Biomedical subjects

N Iwasaki

Publications and source records attributed to N Iwasaki.

At least 55 records · Page 3Linked to original sources

Vascularised fibular grafts. An experience of 102 patients.

The results and complications of 104 vascularised fibular grafts in 102 patients are presented. Bony union was ultimately achieved in 97 patients, with primary union in 84 (84%). The mean time to union was 15.5 weeks (8 to 40). In 13 patients, primary union was achieved at one end of the fibula and secondary union at the other end. In these patients, the mean time to union was 31.1 weeks (24 to 40). Five patients failed to achieve union, with a resultant pseudarthrosis (3 patients) or amputation (2 patients). There were various complications. Immediate thrombosis occurred in 14 cases. In two of 23 patients with osteomyelitis, infection recurred at two and six months after surgery, respectively. Both patients had active osteomyelitis less than one month before the operation. Bony infection occurred in a patient with a synovial sarcoma of the forearm one year after surgery. In 15 patients, 19 fractures of the fibular graft occurred after bony union, all except one within one year after union. In patients in whom an external fixator had been used, fracture occurred soon after its removal. Union was difficult to achieve in cases of congenital pseudarthrosis of the tibia. Appropriate alignment of the fibular graft is an important factor in preventing stress fracture. The vascularised fibula should be protected during the first year after union. Postoperative complications at the donor site included transient palsy of the superficial peroneal nerve in three patients, contracture of flexor hallucis longus in two and valgus deformity of the ankle in three. Vascularised fibular grafts are useful in the reconstruction of massive bony defects. We believe that meticulous preoperative planning, including choosing which vessels to select in the recipient and the type of fixation devices to use, and care in the introduction of the vascularised fibula, can improve the results and prevent complications.

Adolescent↗

Effects of bisphosphonate on matrix metalloproteinase enzymes in human periodontal ligament cells.

BACKGROUND: The host response is a critical component in the pathogenesis of periodontitis. In fact, the clinical benefits associated with regulating the host response have been demonstrated in studies using several different classes of drugs. Biophosphates are one host-modulating class of drugs that has demonstrated this ability. These drugs are clinically effective at reducing bone resorption and have shown the ability to inhibit host degradative enzymes, specifically the matrix metalloproteinases (MMPs). Therefore, the purpose of this study was to investigate the regulatory effects of a bisphosphonate, tiludronate, on MMP levels and activity in human periodontal cells. METHODS: MMP-1 and MMP-3 were assessed in cultured human periodontal ligament cells treated with a bisphosphonate, tiludronate. Reverse transcription-polymerase chain reaction was used to identify mRNA levels for both enzymes, and also for tissue inhibitors (TIMP-1). Enzyme immunoassay (EIA) and immunocytochemistry were used to assess MMP proteins in these cell cultures. Enzyme activity was assessed using FITC-conjugated substrates and quantitated using spectrophotofluorometry. RESULTS: Tiludronate significantly inhibited both MMP-1 and MMP-3 activity in a concentration-dependent manner. A maximal reduction in activity of 35% was achieved for each of the enzymes at a 10(-4) M concentration. Tiludronate did not have a significant effect on the mRNA levels for MMP-1, MMP-3, or TIMP-1. Similarly, there were no effects noted for either MMP-1 or MMP-3 on the protein level. CONCLUSIONS: This study demonstrates an inhibitory effect of tiludronate on the activity of both MMP-1 and MMP-3. These effects appear to occur without altering either mRNA or protein levels for these enzymes, supporting a possible mechanism of action that involves the ability of bisphosphonates to chelate cations from the MMPs. Furthermore, these results support the continued investigation of these drugs as potential therapeutic agents in periodontal disease.

Analysis of Variance↗

Polymyalgia rheumatica and type 2 diabetes mellitus complicated with electromyographic abnormalities that responded well to corticosteroid therapy.

A 62-year-old man who had a 14-year history of diabetes complained of low-grade fever, general malaise, pain of bilateral femurs and hip girdle, and was adniitted to our hospital. The diagnosis of polymyalgia rheumatica (PMR) was made from the clinical symptoms, elevated C-reactive protein and erythrocyte sedimentation rate. Electromyography revealed abnormalities that suggested diabetic peripheral neuropathy. However, the abnormalities were improved after starting treatment with corticosteroids (PSL). After stopping PSL, electric nerve conduction disturbance developed; therefore, it was suggested that peripheral nerve involvement due to PMR was improved by administration of PSL regardless of the existence of diabetic peripheral neuropathy.

Autoimmune Diseases↗

beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY.

The basic helix-loop-helix (bHLH) family of transcription factors plays an important role in the normal development and function of the endocrine pancreas. Heterozygous mutations in the gene encoding one member of this family, NeuroD1/BETA2, are associated with a monogenic form of diabetes that resembles maturity-onset diabetes of the young (MODY) in many respects. This result prompted us to screen the genes encoding related bHLH transcription factors that are also expressed in pancreatic islets for diabetes-associated mutations. We have screened 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in the NeuroD4/Math-3/ATH-3 gene (NEUROD4). This analysis revealed seven frequent polymorphisms that were not associated with MODY, including five in the 5'-untranslated region (UTR) (-477G/A, -436delA, -324delT, -107insTTTT, and -104T/C [cDNA sequences]) and two in the 3'-UTR (1027C/T and 1076C/A). A missense mutation, K68T (203A/C), was found in a heterozygous state in one MODY subject and two nondiabetic subjects. The results of our study suggest that genetic variation in NEUROD4 is not a common cause of MODY in Japanese.

Basic Helix-Loop-Helix Proteins↗

Beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3beta gene (HNF3B) in Japanese patients with maturity-onset diabetes of the young.

Mutations in the transcription factors hepatocyte nuclear factor (HNF)-4alpha and -1alpha, insulin promoter factor-1, and HNF-1beta are the causes of four forms of maturity-onset diabetes of the young (MODY1 and 3-5, respectively). The winged-helix transcription factor HNF-3beta has been implicated in the regulation of expression of each of these MODY genes, suggesting that mutations in the HNF-3beta gene (HNF3B) may also cause MODY. We have tested this hypothesis by screening a panel of 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in HNF3B. This analysis revealed four frequent polymorphisms that were not associated with MODY, including one in the promoter region (-213A/G), two silent mutations in the codons for Ala 97 (291C/T) and Gly 279 (837A/G), and one in the 3'-untranslated region (1424C/T). Two rare substitutions in the 5'-untranslated region, -156C/T and -67A/C, were found in a heterozygous state in two subjects, and two subjects were heterozygous for putative missense mutations, S109N (326G > A) and A328V (983C>T). The two missense mutations were not found in 106 normal chromosomes from nondiabetic subjects. It was not possible to test for co-segregation of these mutations with diabetes and thus, it is unclear whether or not these mutations can cause MODY. The results of our study suggest that mutations in HNF3B are not a common cause of MODY in Japanese subjects.

Adult↗

Analysis and prediction of absorption profile including hepatic first-pass metabolism of N-methyltyramine, a potent stimulant of gastrin release present in beer, after oral ingestion in rats by gastrointestinal-transit-absorption model.

The prediction method for the plasma concentration-time profile of N-methyltyramine (NMT), a potent stimulant of gastrin release present in beer after oral ingestion in rats was examined using the previously developed Gastrointestinal (GI)-Transit-Absorption Model, with the addition of a process of hepatic first-pass metabolism. Phenol red was used as a nonabsorbable marker for estimation of the GI transit rate constant for eight segments in the GI tract. The first order absorption rate constant for each segment was estimated by means of a conventional in situ closed loop method. The results of in situ absorption experiments showed that NMT is well absorbed in the small intestine, especially in the duodenum and jejunum. Using the GI-Transit-Absorption Model, it was demonstrated that more than 90% of orally ingested NMT is absorbed in the small intestine, and that the substantial absorption site for NMT in vivo is the lower jejunum and the ileum. However, the observed bioavailability was only 39.0%. The in vitro metabolism study clarified that NMT is metabolized in the liver, but not in the small-intestinal mucosa. With the hepatic intrinsic clearance value (2.0 liters/h) calculated from the rate of metabolism in vitro, the hepatic availability was estimated to be 0.510 on the basis of a well stirred model, which was validated by two other methods to calculate the hepatic availability of NMT. The plasma concentration-time curve and bioavailability of NMT after oral ingestion were well predicted by the GI-Transit-Absorption Model with the hepatic first-pass metabolism process.

Administration, Oral↗

Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcription factor.

Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction. We have examined the effects of five diabetes-associated mutations (L12H, G191D, R263C, P379fsdelCT, and L584S585fsinsTC) on HNF-1alpha function including DNA binding ability, intracellular localization, and transactivation activity. L12H, P379fsdelCT, and L584S585fsinsTC mutations were found in patients with a clinical diagnosis of MODY, while G191D and R263C mutations were identified in patients diagnosed with type 2 diabetes. These mutations had diverse effects on the functional properties of HNF-1alpha. Comparison of the functional data with clinical information suggested that transactivation activity of mutant HNF-1alpha in beta cells like MIN6 may be the primary determinants of the phenotypic differences observed among diabetic patients with HNF-1alpha mutations.

Adolescent↗

Polymorphism of the beta3-adrenergic receptor gene and weight gain in pregnant diabetic women.

Inappropriate body weight gain during pregnancy has critical effects on the outcome for both mother and fetus. Therefore, body weight gain is an important issue in the management of pregnancy in women with diabetes. A Trp64Arg substitution in the beta3-AR gene has been reported to be associated with body weight gain and obesity in non-insulin-dependent diabetes mellitus (NIDDM) subjects. The aim of this study was to elucidate the contribution of the beta3-AR gene to body weight gain during pregnancy in subjects with diabetes. We analyzed 199 diabetic patients (NIDDM/IDDM; 131/68) and patient data was obtained from the first delivery of each individual. The mean age at diagnosis of diabetes was 22.9 +/- 7.5 years (mean +/- S.D.) and the mean age at delivery was 29.8 +/- 4.5 years. A polymorphism of the beta3-AR gene was detected by PCR-RFLP using Bst OI, which recognizes a Trp64Arg substitution. The frequency of the Trp64Arg allele was 0.15 in NIDDM and 0.17 in IDDM. Among the NIDDM subjects, excess weight gain during pregnancy, as defined by maximum BMI during pregnancy minus basal BMI before pregnancy exceeding five, was observed in 12.2% of the wild-type patients, 19.2% of heterozygotes and 28.6% of homozygotes. Homozygous subjects with NIDDM tended to show excess weight gain during pregnancy, however, this trend did not reach significance. None of the IDDM homozygotes showed excess weight gain. From our study, this beta3-AR gene polymorphism cannot be excluded as a contributing factor to excess weight gain during pregnancy in NIDDM subjects.

Adult↗

Limited wrist fusions: comparison of results 22 and 89 months after surgery.

Limited wrist arthrodeses were performed to treat wrist diseases other than rheumatoid arthritis. The purpose of this study was to evaluate whether clinical and radiographic results noted 22 months after the procedure were maintained on re-examination an average of 89 months (range, 66-148 months) after the procedure. The study comprised 17 wrists. The average patient age was 42 years (range, 11-65 years). Two patients, both with Kienböck's disease, were lost to follow-up. Four radiocarpal and 11 intercarpal arthrodeses were performed. The range of motion between the first and second follow-up examination showed no significant difference. Grip strength likewise was nearly identical at both visits. At the last follow-up visit, progression of osteoarthrosis about the fusion area was noted in only 1 patient. These results suggest that the clinical and radiographic results at 22 months were maintained at the final follow-up visit and that the effect of limited wrist fusion does not deteriorate.

Adolescent↗

Total wrist arthrodesis using bowed crossed K-wires.

A method of total wrist arthrodesis using a combination of autogenous iliac crest bone graft and "bowed" crossed Kirschner wires is described. The method of bowing the K-wires results in a compressive force on the iliac bone graft. This technique resulted in bony union of 22 wrists in 20 patients. The mean time to union was 12 weeks (range, 8-14 weeks). There were no major postoperative complications. The advantages of this technique are its simplicity, versatility, and reliability which mean that special internal fixation devices are not needed.

Adult↗

Distally-based free vascularized tissue grafts in the lower leg.

In the field of orthopaedic surgery, the lower leg is often treated by free vascularized tissue grafts. In performing these grafts for reconstruction of the lower leg, the anterior tibial artery and its venae comitantes are frequently selected as anastomosing recipient vessels. However, due to the deep location of the anterior tibial vessels, it is extremely difficult to accomplish antegrade microsurgical anastomoses between the donor vessels and the anterior tibial vessels. This technical difficulty often leads to the possibility of immediate postoperative arterial and venous occlusion. To resolve this problem, the idea of a reverse-flow island flap has been applied to the free vascularized tissue grafts for reconstruction of the lower leg, based on both artery and vein reconstructed with retrograde blood flow. To evaluate clinical outcomes of the procedure mentioned, the postoperative results of 14 patients were reviewed. The free vascularized grafts consisted of seven vascularized fibular grafts with peroneal flaps, six vascularized latissimus dorsi myocutaneous flaps, and one vascularized groin flap. Venous congestion of the flap was not observed and all flaps survived. Bone union was obtained in seven patients treated with vascularized fibular grafts. There were no serious postoperative complications. Distally-based free vascularized tissue grafts in the lower leg are useful procedures in reconstruction of massive bone defects and osteomyelitis of the tibia, and for skin defects on the anterior aspect of the lower leg.

Adolescent↗

[Renal glucosuria and membranous glomerulonephritis in chronic inflammatory demyelinating polyradiculoneuropathy: CIDP].

Glucosuria was detected in a 7-year-old boy by a routine school mass examination in April 1991. The diagnosis of renal glucosuria was made in the affiliated hospital of the University of Tsukuba. The patient developed muscle weakness and gait disturbance in February 1993. Spinal fluid examination revealed a protein level of 62 mg/dl and a cell count of 4/3. Under the diagnosis of Guillain-Barré syndrome, he was treated with i.v. immunoglobulin and oral prednisolone. Although the therapy somewhat improved the symptoms, his muscle strength had not fully recovered at the end of the treatment. In November 1995, the muscle weakness became worse; he could not go up stairs, nor stand upright on one leg. In April 1996, proteinuria was detected in a school mass examination. He was referred to the University Hospital of Tsukuba for a full renal study in March 1997. Renal biopsy revealed global sclerosis in 16 of 19 glomeruli with extensive interstitial fibrosis and mononuclear cell infiltration. A diagnosis of membranous glomerulonephritis was established based on the findings of spikes in PASM staining, weak IgG deposition in the glomerular capillary and subepithelial deposits by electron microscopic study. Additionally, pituitary growth hormone deficiency was found by endocrinological examination. The diagnosis of CIDP was established by fibulal neuron biopsy, which revealed neuronal degeneration and profound demyelinization. The clinical course of the present case was unlike that of the few reported cases of MGN associated with CIDP described in the literature. The initial renal symptom was glucosuria, which started 5 years prior to the onset of proteinuria. Second, glomerulosclerosis was more extensive than that seen in the literature. We surmise that chronic interstitial nephritis of insidious onset was followed by MGN which developed subsequently, probably at the time of the start of proteinuria.

Adolescent↗

A quantitative study of the progress of myelination in the rat central nervous system, using the immunohistochemical method for proteolipid protein.

The temporal changes in intensity of myelination of the nervous pathways in 0 to 42-day-old Wistar rats were quantitatively analyzed by immunohistochemistry with anti-proteolipid protein and compared with that obtained by immunohistochemistry with anti-myelin basic protein. Immunohistochemistry was performed on paraffin-embedded tissue according to the standard ABC technique. Intensity of myelination was examined by an image analyzing system. We analyzed nine nervous pathways: corpus callosum, optic tract, internal capsule, spinal tract of the trigeminal nerve, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract, medial longitudinal fasciculus, and cuneate fasciculus. The presence of immunoreactive fibers for proteolipid protein (PLP) in the spinal tract of the trigeminal nerve, medial longitudinal fasciculus and cuneate fasciculus was noted on postnatal day 0. Those of the corpus callosum, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract and internal capsule were noted on day 7, and that of optic tract on day 14. The time required to reach the intensity of myelination of day 42 was day 14 for the cuneate fasciculus, day 21 for the spinal tract of the trigeminal nerve, inferior cerebellar peduncle and medial longitudinal fasciculus, day 28 for the optic and pyramidal tracts, day 35 for the corpus callosum and day 42 for the internal capsule and cerebellar white matter. The appearance of immunoreactive fibers for PLP was usually earlier than that for myelin basic protein (MBP) and the pattern of difference between PLP and MBP can be classified into three groups: (1) their time of appearance and progress are almost the same, as in the optic tract; (2) the appearance and progress of PLP occurs earlier than those of MBP, as in the pyramidal tract; (3) the appearance of PLP occurs earlier than that of MBP, but their progress is the same. Our findings revealed that the time of appearance and progress of myelination as measured by PLP are different among the nervous pathways, and that there is also a difference between PLP and MBP. This difference between PLP and MBP may indicate a functional difference between them.

Age Factors↗

Biomechanical analysis of limited intercarpal fusion for the treatment of Kienböck's disease: a three-dimensional theoretical study.

Although several types of intercarpal fusion have been advocated for the treatment of Kienbock's disease, the clinical outcome of each procedure is still inconclusive. The joint load and ligament tension based on a three-dimensional model were measured to determine which intercarpal fusion procedures unload the lunate and whether they alter the force transmission through the entire wrist joint. Ten theoretical models of wrists were used to simulate three different operative procedures: capitate-hamate fusion, scapho-trapezial-trapezoidal fusion, and scaphocapitate fusion. A discrete element analysis technique was used to perform these investigations. The joint force and ligament tension of normal wrists and of simulated operative procedures were calculated according to the deformation of each spring element, simulating the articular cartilage and the carpal ligaments. Scaphocapitate and scapho-trapezial-trapezoidal fusions significantly decreased the joint force at the radiolunate joint and the lunocapitate joint compared with the intact wrist. In contrast, these fusions significantly increased this value at the radioscaphoid joint in comparison with the intact wrist. In the midcarpal joint, scaphocapitate fusion also increased the joint force at the scapho-trapezial-trapezoidal joints and at the triquetral-hamate joint, whereas scapho-trapezial-trapezoidal fusion increased it at the scapho-capitate joint. Capitate-hamate fusion yielded no significant changes of the joint forces through the entire wrist joint. In the analysis of ligament tension, scaphocapitate and scapho-trapezial-trapezoidal fusions significantly decreased the tension only in the dorsal scapholunate ligament. These findings demonstrate that scaph-ocapitate and scapho-trapezial-trapezoidal fusions are effective in decompressing the lunate. By contrast, capitate-hamate fusion is ineffective in reducing lunate compression. Although scaphocapitate and scapho-trapezial-trapezoidal fusions are recommended for the treatment of Kienbock's disease, clinicians should consider that the increase of force transmission through the radioscaphoid and the midcarpal joints may lead to early degenerative changes after these procedures have been performed.

Arthrodesis↗

Structure of the monomeric actin-myosin head complex as revealed by X-ray solution scattering.

In order to study the structure of a complex of monomeric actin and myosin head (S1) in the presence of nucleotide, non-polymerizable G-actin was prepared by the reaction of G-actin with m-maleimidobenzoic acid N-hydroxysuccinimide ester (MBS) and diazonium(1H)tetrazole (DHT). Although singly-modified MBS-actin forms a 2:1 complex with S1, doubly-modified DHT/MBS-G-actin forms a 1:1 complex with a dissociation constant of approximately 10(-6) M and can activate Mg-ATPase of S1 by 2-fold. Using a synchrotron X-ray source, we have measured X-ray solution scattering from reversible acto-S1 complexes obtained by mixing rabbit skeletal S1 and DHT/MBS-G-actin in the absence of nucleotide or in the presence of MgADP. The Guinier plots of the scattering intensity showed straight lines indicating no large aggregates and gave the radii of gyration of the complexes to be 49 and 46 A in the absence and presence of ADP, respectively. The analysis of the scattering curves showed that a monomeric actin binds to a tip of S1, and that the complex undergoes substantial rearrangement resulting in a more compact structure when it binds ADP.

Actins↗