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Biomedical subjects

H Iwata

Publications and source records attributed to H Iwata.

At least 73 records · Page 4Linked to original sources

The anxiolytic effect of Sho-ju-sen, a Japanese herbal medicine, assessed by an elevated plus-maze test in mice.

Sho-ju-sen (SK), a Japanese herbal medicine with a nourishing tonic action, is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) (SS), and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. et Zucc) (PN) and Ginseng roots (Panax ginseng C. A. Meyer) (PX) in the ratio 8:1:1. In this study, an elevated plus-maze test in mice was carried out to assess whether SK had an anxiolytic effect. No significant change was observed in either the plus-maze or activity test following a single administration of SK (10 and 20 mL/kg p.o.). However, mice allowed a free intake of SK (10% solution) for 5 days and longer showed a significant prolongation of the time spent in the open arms (an anxiolytic effect), as long as that caused by the benzodiazepine anxiolytic diazepam (1 mg/kg p.o.). SK (1%, 3% and 30% solutions for 7 days) tended to develop the anxiolytic effect. Of the constituents of SK, SS (8% solution), but not PN (1% solution) or PX (1% solution), resulted in the anxiolytic effect. Except for a slight acceleration in the motor activity by PN (1% solution), no significant change in the motor activity was produced by any treatment with SK, SS or PX. The combined treatment of SK (10% solution) or SS (8% solution) with 1 mg/kg diazepam enhanced the anxiolytic effect. Flumazenil (0.1 mg/kg s.c.), a benzodiazepine receptor antagonist, alone did not change the time spent in the open arms. However, it completely reversed the anxiolytic effect of SK, SS and diazepam. The present results suggest that: (1) long-term treatment with SK develops an anxiolytic effect, (2) SS is the main constituent for the anxiolytic effect of SK, and (3) benzodiazepine receptors are involved in the anxiolytic effect of SK and SS.

Animals↗

Localization of gelatinolytic activity can be detected in breast cancer tissues by film in situ zymography.

BACKGROUND: Extracellular matrix-degrading proteinases secreted by malignant tumor cells have been thought to play an essential role in the processes of invasion and metastasis. However, existence and localization of gelatinase activity in breast cancer tissues have not been clarified. METHODS: We developed a novel film for highly reproducible detection and the localization of gelatinolytic activity. This film has a gelatin layer with a constant thickness 7 microm, and adequate crosslinking to control the speed of degradation by proteases. Cryosections of several breast cancer tissues were put on this gelatin film and incubated for 16 hrs at 37 degrees C. After staining with ponceau 3R dye, the digested area was evaluated under light microscopy. RESULTS: Digestion of gelatin was detected in more than 90%of breast cancer specimens, although it varied in degree and area for each case. In most cases, the gelatinolytic activity was located within cancer nests, and was not detected in stromal cells surrounding cancer cells. The gelatinolytic activity was inhibited by 1,10-phenanthroline, an inhibitor of matrix metalloproteinases (MMPs). CONCLUSIONS: In this study, the localization of net MMP activity was confirmed in breast cancer nest using film in situ zymography. Detailed analysis on the relationship between the strength or distribution of MMP activity and malignancy are anticipated in the future.

Azo Compounds↗

Limited association between a catechol-O-methyltransferase (COMT) polymorphism and breast cancer risk in Japan.

BACKGROUND: Catechol-O-methyltransferase (COMT) inactivates the estradiol metabolites, 2-hydroxy estradiol and 4-hydroxy estradiol. To date, three studies in Caucasians and one study in Chinese have been conducted to determine the association with breast cancer risk of a functional polymorphism (G-to-A, Val158Met) of this enzyme, but the results were inconsistent. In order to examine the impact of this polymorphism on breast cancer risk in Japan, a case-control study was conducted, at Aichi Cancer Center Hospital. METHODS: The cases were 150 patients with histologically confirmed breast cancer who had been diagnosed within 4 years before enrollment at this hospital. The controls were 165 non-cancer patients, mainly from the gastroenterology and breast surgery clinics at the hospital. COMT-H (Val) is the wild-type allele, with high enzyme activity, while the COMT-L (Met) allele has low activity. Genotyping was conducted by a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. RESULTS: The allele frequency of COMT-L was 36.0% for cases and 33.0% for controls. Age-adjusted odds ratios relative to the COMT-HH genotype were 1.46 (95% confidence interval [CI], 0.90-2.36) for COMT-HL, and 0.99 (95% CI, 0.49-2.02) for the COMT-LL genotype. Significant odds ratios were not observed for any subgroup stratified by menopausal status, age at menarche, age at birth of first child, body mass index, and breast cancer history of mother and/or sister(s). CONCLUSION: The present study suggested that any association of the COMT polymorphism with breast cancer risk is limited in Japanese.

Adult↗

Walking ability and activities of daily living after limb salvage operations for malignant bone and soft-tissue tumors of the lower limbs.

We evaluated the number of steps, activities of daily life (ADL) score, Enneking score, active range of motion and muscle strength by muscle manual testing for function in lower limbs after reconstructive procedures in surgical treatment of tumors. The 56 patients with 20 malignant bone tumors and 36 malignant soft-tissue tumors averaged 7119 +/- 3563 steps per day, or 69.8% of the control group. The average ADL score of patients was 14.0 +/- 4.1 points (70.0%), and the average Enneking score 20.4 +/- 6.0 points (68.0%). The scores of the bone tumor group were lower than those of the soft-tissue tumor group. These scores were not correlated with the range of motion. The number of steps and ADL score were correlated with Enneking score (coefficient 0.52 and 0.84, respectively). The number of steps and the ADL score appear to be useful, as is Enneking score.

Activities of Daily Living↗

High tibial osteotomy for varus gonarthrosis: a 10- to 24-year follow-up study.

From January 1976 to December 1990, 66 high tibial osteotomies for medial gonarthrosis were performed in 59 patients. Thirty knees of 26 patients (18 women and 8 men) were reviewed after a mean follow-up period of 15.3 years (range, 10-24 years). The mean age of these 26 patients was 59 years at the time of operation and 75.5 years at the latest follow-up. The average femoro-tibial angle changed, from 187 degrees before surgery to 170 degrees after surgery, and to 174 degrees at the latest follow-up. Progression of osteoarthritic changes was observed in 87% for the medial and in 90% for the lateral compartment of the knee. Clinical results, assessed according to the Japanese Orthopaedic Association (JOA) knee score, showed improvement with a score of 65 points before surgery, and a score of 81 points at the latest follow-up. The overall clinical results were satisfactory for 60% of the knees. The results of this long-term follow-up study show that high tibial osteotomy for medial compartment osteoarthritis can be effective for as long as 15 years.

Aged↗

Epidemiology of low back pain in the elderly: correlation with lumbar lordosis.

We carried out an epidemiologic study to determine the prevalence of low back pain in elderly Japanese and to examine the correlation with lumbar lordosis in sagittal plane radiographs. Low back pain is an enormous clinical and public health problem. With the increasing use of spinal instrumentation, the measurement of lumbar lordosis is thought to be important. However, in elderly Japanese, the prevalence of low back pain and its correlation with lumbar lordosis is not clear. Five hundred and nine people, aged 50-85 years, were examined, and 489 subjects met our criteria. Clinical findings, physical status, and the visual analogue scale (VAS) of pain were examined in these subjects. Measurements and determination of total lordosis from L1-S1 were made from standing radiographs. Forty-eight percent of the subjects had experienced low back pain within the previous 3 months. Women had low back pain more frequently (P = 0.006). There was a significant difference in lumbar lordosis between the groups with and without low back pain (P = 0.0006). Lumbar lordosis was approximately 4 degrees less in the low back pain group and there was no relationship to age or sex in either group. VAS was significantly inversely correlated with lumbar lordosis (P = 0.025, at rest). The body mass index (BMI) of the low back pain group was higher in women, but the difference was not significant (P = 0.06). In conclusion, lumbar lordosis was defined and its prevalence in elderly Japanese was reported together with VAS and physical data used to compare the two groups.

Aged↗

Morphological changes of the anterior spinal artery during aortic cross-clamping and effect of prostaglandin E1 with perfusion.

This investigation was designed to evaluate the morphological changes of anterior spinal artery (ASA) and its reaction to prostaglandinE1 (PGE1) during aortic cross-clamping. ASA during 30 min cross-clamping was observed with charge-coupled device (CCD) and ASA diameter (ASAD) was measured. Group A: Infrarenal aorta was cross-clamped. Group B: Infrarenal aorta was cross-clamped and aorta above the bifurcation was snared. The aortic segment between clamp and snare was perfused with blood. Group C: PGE1 of 100 ng/kg/min was added to perfusate of Group B. The aortic segmental pressures in group B and C were about 30% of the proximal systolic arterial pressure and were significantly higher than distal pressure of group A. After cross-clamping, ASAD decreased about 80% of before cross-clamping in group A. By segmental perfusion of which pressure was about 30% of proximal systolic arterial pressure, ASAD remained almost 90% in group B. By administration of PGE1, ASAD was significantly increased in group C. The changes of ASAD were significantly different between group A and C, and between group B and C.

Alprostadil↗

Bone bonding behavior of the hydroxyapatite containing glass-titanium composite prepared by the Cullet method.

Bioactive composites composed of hydroxyapatite containing glass (HA-G) as a coating and titanium (Ti) or titanium alloy implants as a substrate were prepared by the Cullet method. This method results in the HA-G coating layer on the substrate with a compositional gradient in HA concentration. The results of in vitro and in vivo experiments investigating the characteristics of the composite materials are reported and discussed in this article. In vitro evaluations confirmed that the Cullet method was suitable for the preparation of the functionally gradient composite implants with higher reliable quality. In vivo experiments permitted evaluation of bonding strength of these composite implants to living bone tissue. Mechanical pull-out tests indicated that the implants bonded to living bone at least as firmly as those by the conventional method, and that the adhesion between the HA-G coating layer and metal substrate was well integrated and strongly maintained in vivo. SEM observations with EDX and a histological study of the interface between the HA-G-Ti composite implants and bone tissue revealed not only that the implants bonded to bone directly without any intervening tissue but that bone ingrowth into the HA-G layer occurred. The HA-G-Ti composite implants demonstrate both biocompatible and osteoconductive characteristics, and may be expected to obtain good and lasting results when applied clinically.

Animals↗

Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells.

Naturally occurring neurotoxins, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines (DHTIQs), thought to be the causative agents of Parkinsonism. DHTIQs including norsalsolinol have been found in the mammalian central nervous system. Norsalsolinol can be formed by a non-enzymatic Pictet-Spengler condensation reaction between dopamine and formaldehyde, and has been detected in the urine of Parkinsonian patients. However, the effects of DHTIQs on the secretion of dopamine, as well as other neurotransmitters, are not well understood. This study investigated the effects of norsalsolinol on dopamine secretion from nerve growth factor-differentiated PC12 cells. Norsalsolinol (1-100 microM) pretreatment suppressed both ATP (100 microM)- and K(+) (50 mM)-induced dopamine secretion from PC12 cells in a concentration-dependent fashion, but did not affect basal dopamine secretion. In beta-escin-permeabilized PC12 cells, norsalsolinol pretreatment suppressed Ca(2+) (pCa=4-8)-induced dopamine secretion, but did not inhibit the secretagogue-induced change in intracellular Ca(2+) concentration. These results suggest that norsalsolinol causes the inhibition of secretagogue-induced dopamine secretion from PC12 cells without altering intracellular Ca(2+) concentration. Inhibition of dopamine secretion by norsalsolinol may also be involved in postural abnormality in Parkinson's disease.

Animals↗

A severely brain-damaged case of 3-hydroxyisobutyric aciduria.

We report a male case of 3-hydroxyisobutyric aciduria (3HiB-uria) with severe brain damage. He had mild asphyxia at birth. He needed tube feeding for a month. He showed mild dysmorphic features, including low set ears, a long philtrum and micrognathia. At 4 months of age he had acute encephalopathy. Thereafter, severe brain damage remained and mechanical ventilation care was needed all day. After he had been admitted to our hospital at 3 years of age, repeated organic acid analysis of urine confirmed the diagnosis of 3HiB-uria. This patient had been previously diagnosed as having cerebral palsy and sequelae of acute encephalopathy.

Acidosis↗

Evaluation of spinal cord blood flow during prostaglandin E1-induced hypotension with power Doppler ultrasonography.

STUDY DESIGN: Intraoperative power Doppler ultrasonography was used to evaluate the spinal cord blood flow in cervical spondylotic myelopathy patients during hypotensive anesthesia. OBJECTIVE: To evaluate the effect of prostaglandin E1 (PGE1) induced hypotension on spinal cord blood flow (SBF) during spinal surgery. SUMMARY AND BACKGROUND DATA: Hypotension is frequently induced to decrease blood loss during surgery and to diminish the need for blood transfusion. Prostaglandin E1 (PGE1) is reported to maintain cerebral, liver, and renal blood flow during surgery. However, there are few reports on spinal cord blood flow. METHODS: Eleven patients underwent laminoplasty for cervical spondylotic myelopathy. After a French door type laminoplasty was carried out, hypotension was induced with PGE1. Before and during hypotension, we evaluated blood flow in the anterior spinal cord artery by determining the pulsatility index (PI) and resistance index (RI) using power Doppler ultrasonography. RESULTS: Before hypotension, the mean blood pressure was 80 mmHg. The blood pressure decreased to 60 mmHg using PGE1 (P<0.01), although the PI and RI were significantly higher than before hypotension (PI, P=0.0076 RI, P=0.02). CONCLUSION: The pulsatility and resistance indices during hypotension were significantly higher than before hypotension, suggesting that the autoregulation of the anterior spinal cord artery and anterior spinal cord blood flow were maintained with hypotension using PGE1. Prostaglandin E1 may be a useful drug for hypotensive anesthesia in spinal surgery.

Adolescent↗

Rapidly destructive arthropathy of the hip in haemophilia.

The aetiology of rapidly destructive arthropathy is still being debated. We report a 48-year-old male haemophiliac who exhibited hip arthropathy that was similar to rapidly destructive arthropathy. The hip joint was destroyed 6 months after the onset of symptoms. Results of clinical and laboratory examinations did not show any features of neuropathic, inflammatory or septic arthropathy, except for coagulopathy. Magnetic resonance imaging revealed an expansive joint capsule with synovial proliferation in the affected hip joint. Total hip arthroplasty was carried out successfully with total resection of the synovial tissue and joint capsule. A histological examination revealed bone necrosis, nonspecific inflammation, haemosiderosis and synovial hypertrophy. The recurrent bleeding into the hip joint induced pronounced inflammation with synovial proliferation and acute destruction of bony tissue.

Hemophilia A↗

Possible involvement of IL-12 in reovirus type-2-induced diabetes in newborn DBA/1 mice.

This study extends our previous observations that the reovirus type-2(Reo-2) can induce autoimmune insulitis, which may be mediated by T-helper (Th) 1-dependent mechanisms, resulting in diabetes in newborn DBA/1 mice. In this study mRNA expression for Th1-related cytokines including Th1 and Th2 cytokines in splenic cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR) in relation to the development of insulitis. Furthermore, the effect of monoclonal antibody (MoAb) against interleukin (IL)-12(p40) on the development of insulitis and the mRNA expression in the splenic cells was examined. The mRNA expression for IL-12(p40), IL-18, and interferon (IFN)-gamma, but not IL-5, increased in the spleen in parallel with the development of insulitis. The treatment with MoAb to IL-12(p40) reduced the insulitis with diabetes which was associated with a decrease in the mRNA expression for IL-12(p40), IL-18 and IFN-gamma, and an increase of IL-4 mRNA expression in the spleen. The present study suggested that Th1-dominant systemic immune responses, being responsible for the development of autoimmune insulitis, might be induced by IL-12-induced and IL-18-activated mechanisms.

Animals↗

Calcium phosphate crystal-associated proteins: alpha-2-HS-glycoprotein, prothrombin fragment 1 and osteopontin.

To study the inhibitory effects of calcium phosphate-associated proteins on calcium oxalate crystallization and urinary concentrations of proteins in people who form stones and healthy controls. From 60 L of urine from healthy men, calcium phosphate-associated proteins (alpha-2-HS-glycoprotein, prothrombin fragment 1 and osteopontin) were obtained. The effects of the proteins on calcium oxalate (CaOx) crystallization were studied with a mixed suspension mixed product removal system. To examine urinary concentrations of the proteins, urine samples were collected from 17 healthy subjects and 15 stone formers and analyzed using anion-exchange chromatography and an enzyme immunoassay. Prothrombin fragment 1 (PTF1) and osteopontin (OPN) had strong inhibitory effects on CaOx crystallization, while alpha-2-HS-glycoprotein had a mild inhibitory effect. Urinary concentrations of PTF1 and OPN were lower in stone formers than in healthy controls. Low urinary concentrations of PTF1 and OPN might be one of the reasons for stone formation.

Adult↗

Head penetration into Hylamer acetabular liner sterilized by gamma irradiation in air and in a nitrogen atmosphere.

We reviewed 25 consecutive primary cementless total hip arthroplasties with Hylamer acetabular liners (Hylamer group) and 12 with conventional ultra-high molecular weight polyethylene (Enduron group). Two-dimensional penetration of the femoral head into the liner was determined from anteroposterior radiographs of the pelvis. Head penetration rate was 0.37 mm/y in the Hylamer group sterilized by gamma irradiation in air (n = 6; mean length of follow-up, 3 years), 0.21 mm/y in the Hylamer group sterilized by gamma irradiation in a nitrogen atmosphere (n = 19; mean length of follow-up, 2.7 years), and 0.11 mm/y in the Enduron group (n = 12; mean length of follow-up, 3.9 years). Osteolysis was identified in 6 of the 25 hips with Hylamer liners and 1 of the 12 hips with conventional liners. There was a positive linear correlation between period from production to operation and head penetration rate with Hylamer liner sterilized by gamma irradiation in air and no correlation in a nitrogen atmosphere. Rapid oxidation by irradiation in air might not be the main cause of high rate of wear in Hylamer liners.

Acetabulum↗

Osteosarcoma metastatic to the mandible: a case report.

A case of osteosarcoma that metastasized to the mandibular ramus from the femur in a 36-year-old man is presented. The patient was referred to us for the diagnosis and treatment of swelling of the left cheek. Radiologic examination showed a radiolucent lesion containing radiopaque areas within the left mandibular ramus. The patient previously suffered from a femoral small cell osteosarcoma, which was resected 71 months before our first examination. After induction of general anesthesia, a unilateral mandibulectomy and a simultaneous reconstruction using a titanium plate and an artificial condyle were performed. The postoperative course was uneventful, with satisfactory facial appearance and jaw function. The histopathologic features of the mandibular tumor were identical to those of the femoral tumor. Thus the mandibular lesion was diagnosed as a metastatic small cell osteosarcoma. At 27 months after the operation there had been no recurrence.

Adult↗

Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner.

We investigated the production of hyaluronan (HA) and its effect on cell motility in cells expressing the v-src mutants. Transformation of 3Y1 by v-src virtually activated HA secretion, whereas G2A v-src, a nonmyristoylated form of v-src defective in cell transformation, had no effect. In cells expressing the temperature-sensitive mutant of v-Src, HA secretion was temperature dependent. In addition, HA as small as 1 nM, on the other side, activated cell motility in a tumor-specific manner. HA treatment strongly activated the motility of v-Src-transformed 3Y1, whereas it showed no effect on 3Y1- and 3Y1-expressing G2A v-src. HA-dependent cell locomotion was strongly blocked by either expression of dominant-negative Ras or treatment with a Ras farnesyltransferase inhibitor. Similarly, both the MEK1 inhibitor and the kinase inhibitor clearly inhibited HA-dependent cell locomotion. In contrast, cells transformed with an active MEK1 did not respond to the HA. Finally, an anti-CD44-neutralizing antibody could block the activation of cell motility by HA as well as the HA-dependent phosphorylation of mitogen-activated protein kinase and Akt. Taken together, these results suggest that simultaneous activation of the Ras-mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase pathway by the HA-CD44 interaction is required for the activation of HA-dependent cell locomotion in v-Src-transformed cells.

Animals↗