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Biomedical subjects

H Hashizume

Publications and source records attributed to H Hashizume.

At least 55 records · Page 3Linked to original sources

Experimental spinal fusion using sintered bovine bone coated with type I collagen and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: Posterolateral lumbar transverse process fusion using recombinant human bone morphogenetic protein (rhBMP)-2 carried by sintered bovine bone and Type I collagen complex was compared with fusion achieved using autogeneous bone graft or sintered bovine bone alone. OBJECTIVES: This study examined the efficacy of sintered bovine bone coated with Type I collagen as a carrier of rhBMP-2 for lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: Posterolateral intertransverse process arthrodesis using osteoinductive growth factors is performed experimentally in the lumbar spine. The previous studies revealed the efficacy of osteoinductive factors applied to carriers having no bony structures, such as collagen sheet or polylactic acid polymer, for the spinal fusion. However, in their studies, a large amount of osteoinductive proteins have been applied for the spinal fusion. We used the sintered bovine bone "True Bone Ceramics" (TBC; Koken Co., Tokyo, Japan) coated with type I collagen as the carrier. True Bone Ceramics is the only biomaterial possessing a natural trabecular structure and an organized crystal of bone minerals. METHODS: Twenty-two adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into four groups and had materials implanted as follows: autologous bone group, grafted autologous corticocancellous bone harvested from the posterior iliac crest; implanted TBC group; TBC collagen group, implanted TBC coated with Type I collagen infiltrating into the porous space; and BMP group, implanted sintered bovine bone coated with Type I collagen infiltrated with 100 micrograms of rhBMP-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination 6 weeks after surgery. RESULTS: Two rabbits were killed because of infection and lumbar plexus palsy. Radiographs of the BMP group showed a homogeneous fusion mass at the intertransverse area, and stability was confirmed by dynamic radiographs at 3 and 6 weeks after surgery. In the BMP group, a bony mass in the intertransverse area was more prominent than in the other groups. The BMP group had a higher fusion rate based on manual palpation than the-other groups, and BMP fusions showed significantly higher tensile strength and stiffer fusion. The histologic findings in the BMP group demonstrated membranous bone and endochondral bone formations between the transverse process and the fusion mass. In the other groups, continuous trabecular bone formation was observed in the area surrounding the transverse process, but gaps between grafted fragments and less mature bone formation were present in the intertransverse area. CONCLUSIONS: Sintered bovine bone coated with Type I collagen and rhBMP-2 resulted in a higher fusion rate than the autograft and can be used as a carrier for rhBMP-2 in spinal fusion.

Animals↗

1,3-Disubstituted benzazepines as novel, potent, selective neuropeptide Y Y1 receptor antagonists.

A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R(1) and R(3) substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K(i) values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R(1) and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R(3) in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca(2+) concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

Animals↗

Both D-cis- and L-cis-diltiazem attenuate hydrogen peroxide-induced derangements in rat hearts.

The effects of D-cis- and L-cis-diltiazem on the hydrogen peroxide (H2O2)-induced derangements of mechanical function and energy metabolism, and accumulation of intracellular Na+ were studied in isolated rat hearts. The intracellular concentration of Na+ ([Na+]i) in the myocardium was measured using a nuclear magnetic resonance technique. H2O2 (600 microM) increased the left ventricular end-diastolic pressure, decreased the tissue level of ATP, and increased the release of lactate dehydrogenase from the myocardium. These alterations induced by H2O2 were significantly attenuated by D-cis-diltiazem (15 microM) or L-cis-diltiazem (15 microM). H2O2 (1 mM) produced a marked increase in the myocardial [Na+]i, which was effectively inhibited by tetrodotoxin (3 microM), D-cis-diltiazem (15 microM) or L-cis-diltiazem (15 microM). These results suggest that both D-cis- and L-cis-diltiazem protect the myocardium against the H2O2-induced derangements in the isolated, perfused rat heart. The protective action of D-cis- and L-cis-diltiazem may be due to their ability to inhibit the H2O2-induced increase in [Na+]i, at least in part.

Animals↗

Effects of basic fibroblast growth factor on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit.

STUDY DESIGN: Histologic examination was performed on the autologous intervertebral disc material that was removed from the intervertebral space at L1-L2 and then relocated to the L4 posterior epidural space after the addition of basic fibroblast growth factor (bFGF) in a rabbit. OBJECTIVES: To evaluate whether basic fibroblast growth factor influences the resorption process of the herniated intervertebral disc through the promotion of angiogenesis and chemotaxis. SUMMARY OF BACKGROUND DATA: It has been reported that newly formed vessels, inflammatory cells, and their products may play an important role in the spontaneous resorption process of herniated intervertebral discs. In a rabbit model that mimics the sequestration type of intervertebral disc herniation, it has been reported that the autologous intervertebral disc material that relocated into the epidural space was penetrated by newly formed vessels originating from the epidural fat tissue. Therefore, it is possible that promotion of angiogenesis may influence the resorption of herniated intervertebral discs. Basic fibroblast growth factor is well known as an angiogenesis stimulation factor in vivo. METHODS: Thirty-six adult rabbits were divided into three groups. The L1-L2 intervertebral disc was partially incised through a retroperitoneal approach in each rabbit. The harvested disc material, which contained nucleus pulposus and anulus fibrosus, was immersed in one of three kinds of solution before relocation into the posterior epidural space at L4. In the control group, the harvested intervertebral disc was immersed in physiologic saline for 2 hours before relocation. In the group receiving 5 micrograms bFGF, the disc was immersed in 5 micrograms/mL bFGF for 2 hours before the relocation. In the group receiving 20 micrograms bFGF, the disc was immersed in 20 micrograms/mL bFGF for 2 hours before the relocation. Rabbits of each group were killed for histologic examination 1, 2, 4, and 8 weeks after surgery. RESULTS: In the bFGF-treated groups, newly formed vessels were observed to be in more numerous than those in the control group, 1 and 2 weeks after surgery. The number of inflammatory cells, including macrophages, lymphocytes, and fibroblasts, also increased in the bFGF-treated groups. The period from the surgery to the degradation of the intervertebral disc in the bFGF-treated groups was shorter than that in the control group, although the resorption process of the relocated discs was also observed in the control group. The size of relocated intervertebral discs in the bFGF-treated groups decreased at a higher rate than in the control group as time progressed. The rate of decrease in the size of discs in the group treated with 20 micrograms bFGF was more than that in the group treated with 5 micrograms. CONCLUSIONS: Epidural injection of bFGF facilitated the resorption of the intervertebral disc relocated to the epidural space.

Animals↗

Electromyographic evaluation after endoscopic carpal tunnel release in idiopathic carpal tunnel syndrome.

The purpose of this study was to electromyographically evaluate results in patients with carpal tunnel syndrome (CTS) who underwent endoscopic carpal tunnel release (ECTR). The subjects were 26 patients with idiopathic CTS (37 hands) who were followed for at least 6 months after ECTR. To compare results informatively, hands were classified into four groups: those with normal distal motor latency (DML) and sensory conduction velocity (SCV) were classified as group A, those with normal DML and abnormal SCV as group B, those with an abnormal DML and normal SCV as group C, and those with abnormal DML and SCV as group D. All but one of the hands were classified as group D on the basis of preoperative electromyographic evaluation, while one was classified as group C. The mean preoperative obtainable DML and SCV values were 7.2 m and 27.3 m/s, respectively. Postoperatively, 12 hands were in group A, 8 hands in group B, 2 hands in group C, and 15 hands in group D. The mean DML and SCV values at final follow-up were 4.3 ms and 40.8 m/s, respectively. Of the 25 hands with muscle atrophy before surgery, 6 hands were in group A, 5 hands were in group B, 1 hand was in group C, and 13 hands were in group D at final follow-up. Thenar muscle atrophy and denervation potentials were present before surgery in 13 of the 15 hands classified as group D at the final follow-up.

Adult↗

Sintered bone implantation for the treatment of benign bone tumours in the hand.

We report the results of treatment of benign bone tumours in the hand with curettage and sintered bone implantation using bovine sintered bone (True Bone Ceramics). There were 22 patients who underwent sintered bone implantation in our department in 1984 or later. The follow-up survey period varied from 9 months to 11 years and 2 months (mean, 5.8 years). Recurrence of tumours and complications such as infection or fracture were not observed, and there were no clinical symptoms. X-rays revealed new bone formation connecting the implanted blocks to bone. Sintered bone was not absorbed, and lucent zones around the implants or other abnormal findings were not observed. Bone union was achieved in all patients who had pathological fractures before surgery.

Adolescent↗

Chronic compartment syndrome of the lower leg: a new diagnostic method using near-infrared spectroscopy and a new technique of endoscopic fasciotomy.

A 19-year-old female basketball player had chronic compartment syndrome. During basketball playing, she complained of bilateral lower leg pain that disappeared after several minutes of rest. The intracompartmental pressure in the anterior compartment was 41 mm Hg on the right side and 29 mm Hg on the left side immediately after playing. Prolonged ischemia of the anterior compartment was observed in comparison with four normal controls using near-infrared spectroscopy. Magnetic resonance imaging also revealed that the anterior compartment was mainly affected. Endoscopic fasciotomy was performed using an arthroscope, a transparent outer tube, and a retrograde blade. After the operation, her symptoms disappeared. Three months postoperatively, the anterior compartment pressure decreased and prolonged tissue ischemia improved. Endoscopic fasciotomy allowed us to cut the fascia safely and less invasively. We concluded that this technique is useful in treating chronic compartment syndrome in the anterior compartment of the lower leg.

Adult↗

Three-dimensional appearance of Bowman's layer after radial keratotomy.

PURPOSE: To examine the 3-dimensional collagen fibrillar architecture of Bowman's layer after radial keratotomy (RK). SETTING: Department of Ophthalmology, Niigata University School of Medicine, Niigata, Japan. METHODS: This study used monkey eyes in which 0.3 mm deep radial incisions were made on the cornea 2 weeks and 1, 6, and 12 months before the animals were killed. Corneal buttons were immersed in a fixative and the cells macerated with sodium hydroxide 10%. Scanning electron microscopy (SEM) was performed according to standard procedures. A part of the specimens was embedded in epoxy resin for light microscopic (LM) observation for comparison. RESULTS: The 3-dimensional collagen fibrillar architecture of Bowman's layer was revealed by SEM. The rupture of Bowman's layer could be seen 12 months after surgery and there was no continuity of collagen fibrils in the ruptured area. In LM observations, the width of the stromal incisions gradually became narrower near 12 months after surgery. CONCLUSION: Our cell-maceration/SEM method showed that the rupture of Bowman's layer remained up to 12 months after RK. This suggests that discontinuity of Bowman's layer may be responsible for globe rupture after RK.

Animals↗

1,3-Disubstituted benzazepines as neuropeptide Y Y1 receptor antagonists.

A novel class of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Through a blind screening we found the compound 1-N-(3-(N'-(tert-butoxycarbonyl)amino)benzyl)-7-methoxy-(3-(3)-methyl ureido)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (9: IC50 = 1.6 microM). Chemical modifications of 9 gave a potent NPY Y1 antagonist 3-(N-(4-hydroxyphenyl)-N'-methylguanidino)-1-N-(3-(N'-(tert-butoxy carbonyl)amino)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (14c: IC5(0=43 nM), which had no affinity for NPY Y2 and Y5 receptors.

Benzazepines↗

Simultaneous fracture-dislocations of the distal and proximal interphalangeal joints.

Sixteen cases of simultaneous fracture-dislocations of both the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in the same finger that were treated during the past 10 years were classified into three types: the swan-neck injury (dorsal fragment of the base of the distal phalanx at the DIP joint and palmar fragment of the base of the middle phalanx at the PIP joint); the double-hyperextension injury (palmar fragments at the DIP and PIP joints); and the straight-finger injury (with dorsal and palmar bone fragments at the DIP joint). The results of treatment were more satisfactory in PIP joints than in DIP joints.

Adolescent↗

Inhibition of Na+ channel or Na+/H+ exchanger attenuates the hydrogen peroxide-induced derangements in isolated perfused rat heart.

The effect of tetrodotoxin, a specific inhibitor of the Na+ channel, and 5-(N,N-dimethyl)-amiloride, a specific inhibitor of the Na+/H+ exchanger, on the mechanical and metabolic derangements induced by hydrogen peroxide (H2O2) was studied in the isolated perfused rat heart. The isolated rat heart was perfused aerobically at a constant flow rate and driven electrically. H2O2 (600 microM) decreased the left ventricular developed pressure and increased the left ventricular end-diastolic pressure (i.e. mechanical dysfunction), decreased the tissue levels of adenosine triphosphate and adenosine diphosphate (i.e. metabolic derangement), and increased the tissue level of malondialdehyde (i.e. lipid peroxidation). These mechanical and metabolic derangements induced by H2O2 were significantly attenuated by tetrodotoxin (3 microM) or 5-(N,N-dimethyl)-amiloride (15 microM). Neither tetrodotoxin nor 5-(N,N-dimethyl)-amiloride modified the tissue malondialdehyde level, which was increased by H2O2. In the normal (H2O2-untreated) heart, neither tetrodotoxin nor 5-(N,N-dimethyl)-amiloride affected the mechanical function and energy metabolism. These results suggested that inhibition of the Na+ channel or Na+/H+ exchanger was effective in attenuating the H2O2-induced mechanical dysfunction and metabolic derangements in the isolated perfused rat heart.

Amiloride↗

[Cardiac cell injury induced by lysophosphatidylcholine].

Lysophosphatidylcholine (LPC) is an amphiphilic metabolite produced from membrane-phospholipids by the activation of phospholipase A2 (PLA2), and it accumulates in the ischemic myocardium. It has been demonstrated that exogenous LPC produces an increase in intracellular Ca2+ concentration ([Ca2+]i), morphological change from rod- to round-shape, and increase in release of creatine kinase (CK). The possible mechanism of the Ca2+ overload induced by LPC is direct Ca2+ entry via a nonselective cation channel (or pore) or secondary Ca2+ entry via Na(+)-Ca2+ exchanger after increase in intracellular Na+ concentration. Among anti-ischemic drugs including beta-adrenoceptor antagonists and Ca2+ channel blockers, a drug with high lipophilicity attenuates the LPC-induced cellular damage, probably due to the preservation of membrane integrity. Because LPC, which accumulates during ischemia and reperfusion of the heart, and produces Ca2+ overload, it is possible that LPC potentiates the ischemic injury in the heart. Therefore, development of protective drugs against cell injury induced by LPC would represent a new approach to finding new drugs that protect the heart against ischemic injury.

Animals↗

Protective effect of quinaprilat, an active metabolite of quinapril, on Ca2+-overload induced by lysophosphatidylcholine in isolated rat cardiomyocytes.

We examined the effects of quinaprilat, an active metabolite of quinapril (an angiotensin converting enzyme (ACE) inhibitor) on the increase in intracellular concentration of Ca2+ ([Ca2+]i) (Ca2+-overload) induced by lysophosphatidylcholine (LPC) in isolated rat cardiomyocytes. LPC (15 microM) produced Ca2+-overload with a change in cell-shape from rod to round. Quinaprilat but not quinapril at 20 or 50 microM attenuated the LPC-induced increase in [Ca2+]i and the change in cell-shape in a concentration-dependent manner. Since quinaprilat has an inhibitory action on ACE and quinapril has practically no inhibitory action on ACE, it is likely that the inhibitory action of quinaprilat on ACE is necessary for the protective effect of the drug against LPC-induced changes. We therefore examined the effects of enalapril (another ACE inhibitor with the weak inhibitory action on ACE) and enalaprilat (an active metabolite of enalapril with an inhibitory action on ACE) on the LPC-induced changes. Both enalapril and enalaprilat attenuated the LPC-induced Ca2+-overload, suggesting that the inhibitory action on ACE may not mainly contribute to the protective effect of ACE inhibitors against LPC-induced Ca2+-overload. This suggestion was supported by the fact that neither ACE (0.2 U/ml) nor angiotensin II (0.1-100 microM) increased [Ca2+]i in isolated cardiomyocytes. Furthermore, application of bradykinin (0.01-10 microM) did not enhance the protective effect of quinaprilat against LPC-induced changes. LPC also increased release of creatine kinase (CK) from the myocyte markedly, and quinaprilat but not quinapril attenuated the LPC-induced CK release. Unexpectedly, both enalapril and enalaprilat did not attenuate the LPC-induced CK release. Neither quinapril nor quinaprilat changed the critical micelle concentration of LPC, suggesting that these drugs do not directly bind to LPC. We conclude that quinaprilat attenuates the LPC-induced increase in [Ca2+]i, and that the protective effect of quinaprilat on the LPC-induced change may not be related to a decrease in angiotensin II production or an increase in bradykinin production.

Angiotensin-Converting Enzyme Inhibitors↗

Growth of collagen fibrils produced by human osteosarcoma cells: high-resolution scanning electron microscopy.

To demonstrate three-dimensionally the process of the collagen fibril growth, the bottom of culture dishes with human osteosarcoma cells (NOS-1) and their extracts were examined by conventional scanning electron microscopy (SEM). Backscattered electron (BSE) imaging of SEM was also applied to the specimens, which were stained with phosphotungustic acid and uranyl acetate. Conventional SEM images showed several stages of collagen fibril assembly. Short collagen fibrils with tapered ends were distributed at the bottom of the dish just beneath and/or around the cultured cells; they were 1 microm long and 20-30 nm in diameter at the thickest middle portion. These fibrils were often twisted and united in a right helical direction, and consequently increased in length (5-10 microm) and diameter (more than 100 nm). In BSE images, the periodical bands stained with phosphotungstic acid and uranyl acetate were visualized throughout the individual fibrils. The banding pattern indicated that the polarity of the collagen molecules was unidirectional; namely, that all molecules were pointed in the same direction throughout the length of the fibrils.

Biopolymers↗

Evaluation of release surgery for idiopathic carpal tunnel syndrome: endoscopic versus open method.

To evaluate the usefulness of endoscopic carpal tunnel release (ECTR) on patients with idiopathic carpal tunnel syndrome, multiple aspects of the results of 44 hands (42 patients) treated by ECTR and 40 hands (40 patients) treated by open carpal tunnel release (OCTR) were compared. Results of ECTR were compared with those of OCTR to study not only recovery rate and surgical safety but also cost-effectiveness. Although ECTR was much less invasive than OCTR, recovery of median nerve palsy in the ECTR group was not as good as that in the OCTR group one month after the surgery. Three months after surgery, the palsy of patients treated by ECTR had improved to almost the same extent as in those treated by OCTR. There were no major surgical complications in both ECTR and OCTR groups. The cost and time needed for ECTR treatment was 1/3 of those needed for OCTR. ECTR reduced both cost and treatment time, which is beneficial for both doctors and patients.

Carpal Tunnel Syndrome↗

Ultrasonographic analysis of shoulder rotator cuff tears.

Seventy-nine shoulders suspected of rotator cuff tears were examined by ultrasonography (US) and forty-three received surgery. Long and short axis scans were performed and findings of each were separately classified according to a five-grade system, and the results were correlated with the actual extent of tear observed during surgery. Internal echogenicity and subacromial impingement were analyzed before and after surgery. A accuracy of US in detecting rotator cuff tears was analyzed. In addition, the correlation between cuff shape observed by US before surgery and actual shape observed during surgery was assessed. It was noted that cuff thinning and abnormalities in shape did not recover to normal after surgery. However, in the cases of discontinuities observed by US before surgery, US findings indicated that the torn cuff was anchored to the greater tuberosity and functional during active motion. Although post-operative US findings were not normal, clinical results were good in most cases. Sensitivity of US for detecting rotator cuff tear was 100% and specificity 94%. US is non-invasive, cost effective and allows the physician to examine the joint while it is in motion. Therefore, at this time, we use US as a screening method for detecting rotator cuff tears. Furthermore, US allows us to check for re-tears while the joint is in motion, which is essential for accurate diagnosis.

Adult↗

Adequacy and long-term prognosis of endoscopic carpal tunnel release.

Forty-one hands of 37 patients with idiopathic carpal tunnel syndrome treated by endoscopic carpal tunnel release (ECTR) were followed up for more than one year after surgery. Surgical results were evaluated using Kelly's criteria, the Semmes-Weinstein test, the static and moving 2-point discrimination tests, tip-pinch strength, and motor and sensory nerve conduction studies. Clinical results, according to Kelly's criteria three months after surgery, were excellent or good in 36 hands, and fair or poor in five hands. No recovery was evident at six months and 12 months after surgery in fair and poor hands. Based on these findings, we conclude that a neurolysis of the median nerve and release of constriction of the thenar muscle branch should be performed using the conventional open technique for patients with poor results three months after ECTR if the patients are dissatisfied with ECTR results.

Adult↗

Ultrahigh-vacuum facility for high-resolution grazing-angle X-ray diffraction at a vertical wiggler source of synchrotron radiation.

A versatile ultrahigh-vacuum chamber has been designed for grazing-angle X-ray standing-wave and diffraction experiments at the vertical wiggler source of the Photon Factory. Unlike at other sources, the vertically polarized X-rays from the wiggler favour the use of a horizontal scattering geometry. The X-ray chamber is equipped with a hemispherical beryllium window, which allows any scattering angle to be attained and secondary emissions to be measured. The chamber is of a compact design, sitting on a precision rotary table which is rotated for scans. Samples are introduced from a portable vessel. The whole procedure can be performed in a vacuum better than 10(-7) Pa. The system has successfully been applied to a grazing-angle X-ray standing-wave experiment, which determined the dimer bond length and the domain structure of Si(001) surfaces deposited with monolayer arsenic.

Journal Article↗