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Biomedical subjects

H Hashizume

Publications and source records attributed to H Hashizume.

At least 37 records · Page 2Linked to original sources

Comparative studies of MRI and operative findings in rotator cuff tear.

A prospective study was performed to determine the accuracy of magnetic resonance imaging (MRI) compared with operative findings in the evaluation of patients associated with rotator cuff tears. Fifty-four of 60 shoulders (58 patients) examined by MRI were confirmed as full-thickness tears and 6 as partial-thickness tears at the time of surgery. The oblique coronal, oblique sagittal, and axial planes of T2-weighted images with the 0.5 tesla MRI system were obtained preoperatively and compared with operative findings. MRI correctly identified 46 of 54 full-thickness rotator cuff tears and 5 of 6 partial-thickness tears. A comparison of MRI and operative findings in full-thickness cuff tears showed a sensitivity of 85%, a specificity of 83%, and a positive prospective value (PPV) of 99%. A comparison of partial-thickness tears showed a sensitivity of 83%, a specificity of 85%, and PPV of 39%. Linear regression analysis showed an excellent correlation between the MRI assessment and measurement at the time of surgery (r = 0.90, P < 0.01). MRI was useful in evaluating large and medium-sized rotator cuff tears, but less useful in distinguishing small full-thickness tears from partial-thickness tears.

Adult↗

Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. I. Taxonomy, isolation and biological activities.

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Anti-Bacterial Agents↗

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, isolation, physico-chemical properties and biological activities.

Tyropeptins A and B, new proteasome inhibitors, were isolated from the culture broth of Kitasatospora sp. MK993-dF2. They were purified using ethyl acetate extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC. Tyropeptin A inhibited the chymotrypsin-like (ChT-L) and trypsin-like (T-L) activities of 20S proteasome with IC50 values of 0.1 microg/ml and 1.5 microg/ml respectively, but did not inhibit the peptidylglutamyl-peptide hydrolyzing (PGPH) activity of 20S proteasome at a concentration of 100 microg/ml. The inhibitory activities of tyropeptin A were about two times as strong as that of tyropeptin B. Taxonomy of the producing strain is also described.

Animals↗

Time course changes of nerve conduction velocity in idiopathic carpal tunnel syndrome after endoscopic surgery.

A total of 49 patients (71 hands) underwent endoscopic carpal tunnel release according to the method of Okutsu accompanied by electrophysiological studies performed for idiopathic carpal tunnel syndrome at our department between August 1993 and May 1998. Among them, 41 patients (55 hands) who were followed-up for 12 months or more postoperatively were studied. The clinical outcome was favorable in 50 out of 55 hands (90.9%). In the 5 hands showing poor surgical results, distal motor latency or sensory nerve conduction velocity was not recordable before surgery and had not improved at 1 month postoperatively. In the present study, it is highly likely that the long-term prognosis will be poor when distal motor latency or sensory nerve conduction velocity is not recordable at 1 month after surgery as well as preoperatively. It is possible to identify patients with a poor outcome by performing electrophysiological studies at 1 month after surgery.

Adult↗

Spinal glial activation and cytokine expression after lumbar root injury in the rat.

STUDY DESIGN: This study was designed to examine the behaviorial immunohistochemical changes of spinal glial cells and spinal Interleukin (IL)-1beta expression after various nerve root injuries used as models of lumbar radiculopathy. OBJECTIVES: In order to better understand the role of central inflammation in the pathophysiologic mechanisms that give rise to pain associated with lumbar radiculopathy, this research studied the relationship between pain-related behavior associated with spinal glial activation and IL-1beta expression generated by three types of nerve root injury: loose ligation with chromic gut, loose ligation with silk, and tight ligation with silk. SUMMARY OF BACKGROUND DATA: An animal model of lumbar radiculopathy originally described by Kawakami and Weinstein involved loose ligation of unilateral L4-L6 nerve roots with chromic gut. Characterization and establishment of such an animal model of low back pain enables further investigation of the nature of the pathophysiologic mechanisms associated with lumbar radiculopathy in humans. METHODS: Seventy-three rats were divided into four treatment groups. Chromic group (n = 25): The L5 nerve roots (dorsal and ventral) were exposed by hemilaminectomy and loosely ligated with chromic gut. Tight silk group (n = 18): The exposed L5 nerve roots were tightly ligated extradurally with 5-0 silk suture. Loose silk group (n = 15): two loose ligatures of 5-0 silk were placed around the exposed L5 nerve roots. Sham group (n = 15): the rats were subjected to laminectomy alone for exposing nerve roots. Following surgery, thermal hyperalgesia and mechanical allodynia was assessed time-dependently up to 42 days post operatively. At 1, 3, 7, 14, and 42 days postoperatively, the rats in each group were perfused with fixative. The L5 spinal cord segments was harvested and cryosectioned for glial and cytokine immunohistochemistry. RESULTS: In the chromic and the tight silk group, an immediate and sustained mechanical allodynia was observed in the ipsilateral hind paw up to 35 days postoperatively. The loose silk group also showed an immediate mechanical allodynia that subsided by 14 days postoperatively. Sham-treated animals exhibited mild mechanicalallodynia for the initial 7 days after the surgery. Thermalhyperalgesia was evident in the three primary treatment groups, but not in the sham-treated rats. OX-42 expression was elevated in the gray matter of the L5 spinal section by 3 days in the chromic, the tight silk, and the loose silk groups as compared to the sham group. Astrocytic activation increased over time in all groups except the sham group. There was no direct correlation between degree of microglial response and severity of pain behaviors. In contrast, astrocytic activation demonstrated a direct relationship with the elevation of mechanical allodynia for the first 7 days. In addition, spinal IL-1beta protein expression was increased bilaterally in the superficial layer of the dorsal horn and cell nuclei of the ventral horns in the ligature treated groups as compared with the sham group. CONCLUSION: Direct mechanical and/or chemical injury to lumbar roots in the rat gives rise to pain behavior suggestive of lumbar radiculopathy. The finding that glial activation and enhanced IL-1beta expression are observed in the spinal cord after root injury supports a central, neuroimmune component in the generation of lumbar radiculopathy. A further understanding of the immunologic consequences of root injury may lead to further development and the novel use of selective cytokine-inflammatory inhibitors for the treatment of low back pain associated with radiculopathy.

Animals↗

Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis.

H-2K(b)-restricted tumor epitope peptides, including tyrosinase-related protein 2 residues 181-188 (TRP-2) and connexin 37 residues 52-59 (MUT1), were applied to permeability barrier-disrupted C57BL/6 (B6) mouse skin from which the stratum corneum of the epidermis had been removed by tape-stripping. This procedure primed tumor-specific cytotoxic T lymphocytes (CTLs) in the lymph nodes and spleen, protected mice against subsequent challenge with corresponding tumor cells, and suppressed the growth of established tumors. Preventive and therapeutic effectiveness was correlated with the frequency of tumor-specific CTL precursors. MHC class II Ia(b+) cells separated from tape-stripped skin, compared with those from intact skin, exhibited a strong antigen-presenting capacity for CTL, suggesting that CTL expansion after peptide application is primarily mediated by epidermal Langerhans cells. Thus, percutaneous peptide immunization via barrier-disrupted skin provides a simple and noninvasive means of inducing potent anti-tumor immunity which may be exploited for cancer immunotherapy.

Administration, Cutaneous↗

Mechanical compression of the lumbar nerve root alters pain-related behaviors induced by the nucleus pulposus in the rat.

The purpose of this study was to refine a method of nerve-root injury in the rat to produce hyperalgesia, a pain-related behavior, and to determine if there were any relationships between the histological extent of nerve-root injury and the magnitude of hyperalgesia. Three methods were used to produce hyperalgesia: irritation of a nerve root by ectopic nucleus pulposus, silk loop alone, or both silk loop and ectopic nucleus pulposus. Autologous nucleus pulposus obtained from coccygeal intervertebral discs was relocated on the lumbar nerve roots after laminectomy. Two loops of 4-0 silk were placed around the exposed nerve roots. Hyperalgesia was measured preoperatively and postoperatively. The distribution of myelinated axons in the dorsal nerve roots was evaluated histologically. Mechanical hyperalgesia was detected in rats in which autologous nucleus pulposus was applied to the nerve root but not in those in which silk loops were used. Silk loops around the nerve root resulted in thermal hyperalgesia only in rats in which autologous nucleus pulposus was applied to the nerve root. Fewer large myelinated fibers were seen in the rats in which silk loops were used. Although a silk loop around the nerve root was not sufficient to produce hyperalgesia, supplemental application of autologous nucleus pulposus to the nerve root produced thermal hyperalgesia. It is possible that mechanical constriction of the nerve root alters the pain-related behavior elicited by chemical factors from the nucleus pulposus.

Animals↗

Cyclooxygenase-2 inhibitor SC-236 attenuates mechanical allodynia following nerve root injury in rats.

Low back pain is a common problem, affecting approximately two-thirds of the adult population. Of these individuals, a significant percentage will exhibit symptoms of radicular pain or sciatica. The purpose of this study was to determine the effect of one systemic (2 mg/kg) or intrathecal (0.2 mg/kg) dose of a selective cyclooxygenase-2 inhibitor (SC-236) in decreasing existing mechanical allodynia in a rat model of radiculopathy. Gait disturbance and mechanical allodynia (increased response to non-noxious von Frey monofilament stimuli) were assessed daily until the rats were killed 7 days after surgery. Robust mechanical allodynia developed in the rats in all groups except for those in the sham group by day 1 after surgery. Mechanical allodynia was significantly lower in the rats that received the systemic or the intrathecal dose of SC-236 than in those in the vehicle control group (analysis of variance followed by Bonferroni multiple comparison test, p = 0.002). The intrathecal drug route of administration produced greater attenuation in allodynia than the systemic dose, supporting a central mechanism of action of the cyclooxygenase-2 inhibitor (p = 0.002). The hypothesis that cyclooxygenase-2 is involved in spinal nociceptive processing after a nerve root injury was supported by this study. In addition, these data support continued basic science research to further elucidate central inflammatory processes that follow nerve root injury.

Animals↗

Openings between defective endothelial cells explain tumor vessel leakiness.

Leakiness of blood vessels in tumors may contribute to disease progression and is key to certain forms of cancer therapy, but the structural basis of the leakiness is unclear. We sought to determine whether endothelial gaps or transcellular holes, similar to those found in leaky vessels in inflammation, could explain the leakiness of tumor vessels. Blood vessels in MCa-IV mouse mammary carcinomas, which are known to be unusually leaky (functional pore size 1.2-2 microm), were compared to vessels in three less leaky tumors and normal mammary glands. Vessels were identified by their binding of intravascularly injected fluorescent cationic liposomes and Lycopersicon esculentum lectin and by CD31 (PECAM) immunoreactivity. The luminal surface of vessels in all four tumors had a defective endothelial monolayer as revealed by scanning electron microscopy. In MCa-IV tumors, 14% of the vessel surface was lined by poorly connected, overlapping cells. The most superficial lining cells, like endothelial cells, had CD31 immunoreactivity and fenestrae with diaphragms, but they had a branched phenotype with cytoplasmic projections as long as 50 microm. Some branched cells were separated by intercellular openings (mean diameter 1.7 microm; range, 0.3-4.7 microm). Transcellular holes (mean diameter 0.6 microm) were also present but were only 8% as numerous as intercellular openings. Some CD31-positive cells protruded into the vessel lumen; others sprouted into perivascular tumor tissue. Tumors in RIP-Tag2 mice had, in addition, tumor cell-lined lakes of extravasated erythrocytes. We conclude that some tumor vessels have a defective cellular lining composed of disorganized, loosely connected, branched, overlapping or sprouting endothelial cells. Openings between these cells contribute to tumor vessel leakiness and may permit access of macromolecular therapeutic agents to tumor cells.

Animals↗

A stress distribution analysis of a ceramic lunate replacement for Kienbock's disease.

To determine the usefulness of a ceramic lunate replacement for the wrist joint as a possible treatment for Kienböck's disease, stress distribution of five wrist joint models (a normal wrist, one with the lunate bone removed, one with a coiled tendon replacement, one with a coiled tendon replacement with a ceramic core, and one with a ceramic lunate replacement coated with sheets of tendon) were analysed by the finite element method. The results of finite element method analyses were compared with those of pressure distribution analyses on the wrist joint using pressure-sensitive film and measurement of pressure on the radio-lunate joint with a tactile sensor. Both the coiled tendon model and ceramic core model were unable to resist applied force. Stress and pressure were well-distributed in the wrist joint of the ceramic lunate implant model. These results indicate that the ceramic lunate implant could be expected to prevent carpal collapse.

Cadaver↗

An experimental approach to spinal fusion using sintered bovine bone in a pig model.

Sintered bovine bone is a biomaterial based on calcium phosphate, an organized crystal of bone mineral that possesses a natural trabecular structure. The authors considered whether sintered bovine bone can integrate with recipient bone and adjust to the strength of recipient bone for anterior spinal fusion in an animal model. Either autologous iliac bone or sintered bovine bone was implanted for a spinal body fusion. Some pigs underwent exposure of the spinal bodies without implantation. Based on radiographic evaluation, manual palpation, biomechanical testing, and histologic examination, spinal fusion with sintered bovine bone resulted in a composition and structure similar to that of the autograft (or of no implantation). The sintered bovine bone with its moderate strength tended to adjust to the bone stiffness of the host bone in the specimens as new bone grew.

Animals↗

Ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the isolated, perfused rat heart.

The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl-L-carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl-L-carnitine (4 microM) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl-L-carnitine were attenuated by ranolazine (5, 10, and 20 microM) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mM) did not attenuate palmitoyl-L-carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl-L-carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase.

Acetanilides↗

Scanning electron microscopic studies of the vascular smooth muscle cells and pericytes in the rat heart.

The cytoarchitecture of smooth muscle cells and pericytes in the rat cardiac vessels was studied by scanning electron microscopy after the removal of connective tissue matrices using a modified KOH-collagenase digestion method. The initial stem of the coronary arteries had groups of smooth muscle cells which ran in various directions on the outermost layer of the media. Although smooth muscle cells in coronary arteries of more than 100 microm in the outer diameter were arranged in a rough circle around the vessel axis, oblique and/or longitudinal muscle bundles were often present in the medio-adventitial border of the vessels. The presence of irregularly oriented muscular bundles is probably connected with resistance against the stretching force induced by the beating of the heart. As the vessel size decreased toward the periphery, almost all of the smooth muscle cells became spindle-shaped with several tiny processes and ran circularly or helicaly to the vessel axis. In the precapillary arterioles (6-12 microm), smooth muscle cells acquired various cytoplasmic processes which helicaly surrounded endothelial cells. Unmyelinated nerves were often associated with arterioles. Blood capillaries were morphologically divided into three segments: arterial capillaries which had pericytes with wide and circularly oriented processes, true capillaries whose pericytes extended long and thin primary processes bilaterally along the vessel axis, and venous capillaries surrounded irregularly and loosely by wide pericytic processes. The stellate pericytes in the postcapillary venules (10-30 microm) gradually changed into flat tape-like smooth muscle cells, which ran circularly in the collecting venules and veins (30-200 microm). The large collecting veins were finally overwhelmed by superficial thin layer of the myocardium, their own smooth muscle cells being very sparse. This suggests that large veins have poor ability to contract by themselves but are influenced by the surrounding myocardial cells.

Animals↗

The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy.

The present study was designed to analyze the subfibrillar structure of corneal and scleral collagen fibrils by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Isolated collagen fibrils of the bovine cornea and sclera were fixed with 1% OsO4, stained with phosphotungstic acid and uranyl acetate, dehydrated in ethanol, critical point-dried, metal-coated, and observed in an in-lens type field emission SEM. Some isolated collagen fibrils were fixed with 1% OsO4, dehydrated, critical point-dried and observed without metal-coating in an AFM. Isolated collagen fibrils treated with acetic acid were also examined by SEM and AFM. SEM and AFM images revealed that corneal and scleral collagen fibrils had periodic transverse grooves and ridges on their surface; the periodicity (i.e., D-periodicity) was about 63 nm in the cornea and about 67 nm in the sclera. Both corneal and scleral collagen fibrils contained subfibrils running helicoidally in a rightward direction to the longitudinal axis of the fibril; the inclination angle was about 15 degrees in the corneal fibrils and 5 degrees in the scleral fibrils. These findings indicate that the different D-periodicity between corneal and scleral fibrils depends on the different inclinations of the subfibrils in each fibril. The present study thus showed that corneal collagen fibrils differ from scleral collagen fibrils not only in diameter but also in substructure.

Animals↗

Hemodialysis-related subacromial lesion: diagnostic imaging and minimally invasive treatment.

BACKGROUND: In an attempt to refine the diagnosis and surgical treatment system for spontaneous shoulder pain in supine position (SPSP) in long-term hemodialysis (LTHD) patients we reviewed shoulders of patients during a 4-year period. PATIENTS AND METHODS: Clinical findings, imaging findings and operative results (average duration of follow-up was 39 months) on both shoulders of 110 patients (Shigei Hospital, Okayama, Japan) were analyzed to identify the cause of SPSP in order to accurately differentiate it from other shoulder pains, and to select the proper treatment method. RESULTS: As the hemodialysis period lengthened, increase in the incidence and severity of bone and soft tissue changes (radiolucency, joint destruction, increase of thickness of subacromial bursa and rotator cuff, and synovial proliferation) in the shoulder induced by dialysis-related amyloidosis were noted in roentgenography, ultrasonography and magnetic resonance imaging. SPSP occurred in the LTHD patients. An increase in subacromial bursa and rotator cuff thickness correlated with SPSP. A decrease in subacromial space correlated with change in position and SPSP. An increase of subacromial pressure was judged to be the cause of SPSP, and subacromial decompression by coraco-acromial ligament release was effective for relieving SPSP. When massive synovial proliferation or invasion of granulation tissues was observed in the glenohumeral joint, arthroscopic debridement was necessary. CONCLUSION: SPSP is a sensitive indicator of a distinct subacromial lesion frequently found in LTHD patients. These lesions can be treated by minimally invasive endoscopic coraco-acromial ligament release, resulting in marked pain relief.

Arthroscopy↗

Effects of CP-060S, a novel Ca(2+) channel blocker, on oxidative stress in cultured cardiac myocytes.

The effect of (-)-(S)-2-[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3, 4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thiazolidin- 4-one hydrogen fumarate (CP-060S), a novel Ca(2+) channel blocker, on hydrogen peroxide (H(2)O(2))-induced cytotoxicity was studied in cultured rat cardiac myocytes. The CP-060S effect was compared with that of CP-060R, an optical isomer of CP-060S with a less potent Ca(2+) channel blocking action than CP-060S. H(2)O(2) increased the release of lactate dehydrogenase from cardiac myocytes and decreased the formation of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) formazan in cardiac myocytes (i.e., cytotoxic action). Both CP-060S (1 microM) and CP-060R (1 microM) attenuated to a similar extent the foregoing alterations induced by H(2)O(2). On the other hand, 1,3-dimethyl-2-thiourea (10 mM), a scavenger of both H(2)O(2) and hydroxyl radical, also attenuated the H(2)O(2)-induced cytotoxicity whereas diltiazem (10 microM) did not. In an experiment using electron spin resonance (ESR) with 5, 5-dimethyl-1-pyrroline N-oxide (DMPO), a spin-trapping agent, both CP-060S and CP-060R decreased the intensity of DMPO-hydroxyl radical signal concentration dependently. These results suggest that CP-060S protects cardiac myocytes from oxidative stress through its radical scavenging action.

Animals↗

Differential inhibition of HMG-CoA synthase and pancreatic lipase by the specific chiral isomers of beta-lactone DU-6622.

A synthetic beta-lactone trans-DU-6622 (3-hydroxy-2-(hydroxymethyl)-5-[7-(methylcarbonyl)-naphthalen++ +-1-yl]pentanoic acid 1,3-lactone, a mixture of (2R, 3R)- and (2S, 3S)-beta-lactones) was found to inhibit HMG-CoA synthase (IC(50): 0. 15 microM) and pancreatic lipase (IC(50): 120 microM). The effects of the optically pure DU-6622 isomers on the two enzymes were compared. The (2R, 3R)-isomer was shown to be a highly specific inhibitor of HMG-CoA synthase (IC(50): 0.098 microM vs 270 microM for pancreatic lipase), while the (2S, 3S)-isomer markedly increased the specificity of lipase inhibition (IC(50): 27 microM vs 31 microM for HMG-CoA synthase). Furthermore, the (2R, 3R)-isomer strongly inhibited the binding of [(14)C]hymeglusin to HMG-CoA synthase, indicating that the isomer was bound to the same site of the synthase as hymeglusin. The (2R, 3R)-beta-lactone is responsible for the specific inhibition of HMG-CoA synthase, while the (2S, 3S)-beta-lactone is responsible for the inhibition of pancreatic lipase.

Animals↗