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Biomedical subjects

S Katoh

Publications and source records attributed to S Katoh.

At least 127 records · Page 7Linked to original sources

Neurologic outcome in conservatively treated patients with incomplete closed traumatic cervical spinal cord injuries.

STUDY DESIGN: The neurologic outcomes in patients with conservatively managed incomplete closed traumatic cervical spinal cord injuries was evaluated using the motor scoring system and the Frankel classification. OBJECTIVES: To show that the motor scoring of recovery system combined with functional Frankel grading will make the documentation of final neurologic outcome more accurate for future comparisons of various methods of treatment. SUMMARY OF BACKGROUND DATA: The influence of surgical and pharmacologic methods of treatment on recovery remains debatable. METHODS: Sixty-three consecutive patients with incomplete cervical injuries who were admitted to the hospital within 2 days after injury were included. All patients were treated conservatively with 6 weeks of bedrest and 6 weeks of mobilization with neck support. RESULTS: Five patients had neurologic deterioration, and all but one patient recovered without surgery. The evaluation of 44 patients who were observed for more than 12 months showed that the preservation of sharp sensation below the level of injury was an indicator of a good prognosis in patients whose injuries were classified as Frankel B, and the degree of recovery of these patients according to the motor score system was comparable with that of patients who were classified as Frankel C. All patients classified as Frankel C who did not deteriorate recovered in Frankel grade. All but one of the patients in the Frankel D group recovered full motor power. The degrees of motor deficit and recovery did not correlate with the mechanism or the degree of the injury of the spinal axis. CONCLUSION: Conservative treatment remains a good option for patients with incomplete cervical cord injuries. It is hoped the current study will be a good basis for comparison of the neurologic outcomes of different treatment modalities.

Adolescent↗

Induction and its spread of apoptosis in rat spinal cord after mechanical trauma.

This study was undertaken to examine the spinal cord of rats after trauma for the induction of apoptosis. DNA ladder formation was demonstrated by gel electrophoresis of the DNA obtained from the spinal cord at the site of injury after trauma from 12 h to 8 days and was most significant on Days 3 and 4. As for the longitudinal spread of the injury in the spinal cord, the ladder formation was observed in the two segments adjacent to the site of trauma 3 days after trauma. Histological examination using in situ end labeling also demonstrated the appearance of apoptosis. These results provide the evidence for the induction of apoptosis in the spinal cord after trauma in rats.

Animals↗

Growth of the cervical spine with special reference to its lordosis and mobility.

STUDY DESIGN: The cervical spine of the healthy Japanese children aged between 1 year and 18 years was radiographically examined. OBJECTIVES: To examine the correlation between growth of the cervical vertebral body and the facet joint and the development of the cervical lordosis and intervertebral motion. SUMMARY OF BACKGROUND DATA: Although the growth of body height and facet angle have been well documented, their correlation with curvature or mobility has not been elucidated. METHODS: We evaluated plain lateral radiographs of 180 boys and 180 girls regarding diameters and central heights of the cervical vertebra, the anterior and posterior vertebral height ratio, body height index, the facet joint angles, and tilting and sliding motions. Cervical length as the summation of the central height from C3 to C7 and the cervical lordosis angle (C3-C7 angle) were also measured. RESULTS: The mean C3-C7 angle and body height index gradually decreased until 9 years of age and then increased. The C3-C7 angle showed a significant correlation with cervical length, body height index, and facet joint angles before 9 years of age, and with cervical length and body height index after 9 years of age but not with facet joint angles. Facet joint angle decreased until 10 years of age and remained almost unchanged thereafter. Total sliding showed a significant age-related decrease and showed a significant correlation with facet joint angle. CONCLUSION: Although the lordosis angle showed a significant correlation with the other values, cervical length, body height index, and facet joint angle, the determinants of the lordosis could not be elucidate in the present study. As for the mobility of the cervical spine, changes of tilting motion were small, whereas changes of sliding motion were restricted by the change of orientation of the facet joints.

Adolescent↗

Synthesis and selective coronary vasodilatory activity of 3,4-dihydro-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol derivatives: novel potassium channel openers.

A variety of compounds having a benzopyran such as levcromakalim generally exhibit potent antihypertensive activity. During extensive investigations aimed toward identifying K+ channel openers having selective coronary vasodilation without potent hypotensive and tachycardiac effects, we synthesized a series of 3,4-dihydro-2H-1-benzopyran-3-ol derivatives modified at positions 2, 4, and 6 in the benzopyran ring. Initially, compounds having two methoxymethyl groups at position 2 were found to show a selective effect on coronary blood flow (CoBF) relative to mean arterial pressure (MAP) in anesthetized dogs. To find more potent vasodilators, various benzopyran derivatives modified at position 4 were synthesized and structure-activity relationships were examined by evaluation of the extent and duration of the increase in CoBF in anesthetized dogs. As a result, compounds having a (1,6-dihydro-6-oxopyridazin-3-yl)amino group at position 4, in addition to the two methoxymethyl groups at position 2, were found to be more potent and to have an improved duration of action. Among these compounds, JTV-506, (-)-(3S,4R)-6-cyano-3,4-dihydro-4-[(1,6-dihydro-1-methyl-6-oxopyridaz in-3-yl)amino]-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol, exhibited good selectivity for its effect. Administration of this compound (0.03 mg/kg, p.o.) elicited an increase of CoBF without a change of systemic blood pressure and heart rate (HR) in conscious dogs. Further evaluation was performed with respect to (i) the selectivity of its action on the coronary artery versus the aorta and (ii) its effects on MAP, HR, and electrocardiographic ST elevation. As a result, JTV-506 was selected as a potent and selective coronary vasodilator with various pharmacological features favoring clinical development.

Animals↗

Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad.

Proteolytic processing of capsid assembly protein precursors by herpesvirus proteases is essential for virion maturation. A 2.5 A crystal structure of the human cytomegalovirus protease catalytic domain has been determined by X-ray diffraction. The structure defines a new class of serine protease with respect to global-fold topology and has a catalytic triad consisting of Ser-132, His-63, and His-157 in contrast with the Ser-His-Asp triads found in other serine proteases. However, catalytic machinery for activating the serine nucleophile and stabilizing a tetrahedral transition state is oriented similarly to that for members of the trypsin-like and subtilisin-like serine protease families. Formation of the active dimer is mediated primarily by burying a helix of one protomer into a deep cleft in the protein surface of the other.

Amino Acid Sequence↗

Role of cytokines in leukemic type growth of myelodysplastic CD34+ cells.

The clonal growth of progenitor cells from myelodysplastic syndromes (MDS) can be subdivided into four growth patterns: (1) normal, (2) no growth or low plating efficiency, (3) low colony and high cluster number, and (4) normal or high colony number with a large number of clusters. The former two (1 and 2) can be referred to as nonleukemic patterns and latter two (3 and 4) as leukemic. In a search for a role for cytokines in leukemic-type growth of MDS progenitor cells, marrow CD34+ cells were purified up to 94% for 8 normal individuals and 88% for 12 MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). The purified CD34+ cells were cultured for 14 days with various combinations of cytokines, including recombinant human macrophage colony-stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte-macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3), and stem cell factor (SCF; a ligand for c-kit) in serum-free medium. The clonal growth of MDS CD34+ cells supported by a combination of all of the above cytokines was subdivided into the two patterns of leukemic or nonleukemic, and then the role of individual or combined cytokines in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. Evidence we obtained showed that SCF plays a central role in the leukemic-type growth of MDS CD34+ cells and that G-CSF, GM-CSF; and/or IL-3 synergize with SCF to increase undifferentiated blast cell colonies and clusters over that seen in normal CD34+ cells. SCF is present in either normal or MDS plasma at a level of nanograms per milliliter, and this physiologic concentration of SCF can stimulate progenitor cells. This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blast cells. This depends, at least in part, on cytokines such as G-CSF, GM-CSF, IL-3, and SCF.

Acute Disease↗

Use of peptide immunization for porcine insulin of a very high homology with a host protein.

An anti-peptide antibody was obtained against a peptide corresponding to the 12 amino acids of the C-terminal region of porcine insulin B chain. The adsorption characteristics of this antibody were compared with those of anti-porcine insulin and anti-sheep insulin antibodies. Immunization of rabbits using the peptide corresponding to the C-terminal region of porcine insulin B chain produced an anti-peptide antibody which reacted with native porcine insulin with a much higher association constant than that of an anti-porcine insulin antibody. In addition, this immunization technique did not cause any observable physiologically harmful effects, such as hypoglycemia, in the immunized rabbits. Thus, peptide immunization may be a useful strategy when target proteins have biological activity and/or toxicity, and also have a very high degree of homology with the corresponding proteins of the immunized animal, which may inhibit the production of antibodies with a high association constant.

Adsorption↗

Morphologic analysis of the facet joint in the immature lumbosacral spine with special reference to spondylolysis.

STUDY DESIGN: Morphological analysis was performed of the facet joint of the normal and spondylolytic lumbosacral spine in children and adolescents. OBJECTIVES: This study was performed to estimate the influence of spondylolysis on growth of the neural arch of the lumbosacral spine. SUMMARY OF BACKGROUND DATA: The development of the facet joint and its relation to spondylolysis have not been documented in the literature. METHODS: The dimension and orientation of the facet joint at L5/S were measured on radiographs and computed tomography scans from 144 boys without pars defects and 104 boys with pars defects. The latter group was further investigated according to the stage of pars defects. Patients in both groups were between 9 and 18 years of age. RESULTS: Growth of the facet joint in the sagittal and transverse directions and the increase of the transverse angle were remarkable up to approximately 13 years of age. Concavity of the facet joints also progressed in children of the same age. The growth of the facet joint in patients with spondylolysis was significantly retarded as the pars defects advanced from the progressive to the terminal stage. The joint surface was more coronal in orientation and flatter in shape compared with controls. CONCLUSIONS: The present results suggest that pars defects occurring in children disturb or retard the growth of the facet joint and that the morphological characteristics of the joint surfaces in patients with spondylolysis are the consequence of these defects.

Adolescent↗

Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin.

Fumonisin B1 (FB1), a mycotoxin produced by the fungus Fusarium moniliforme, which is a common contaminant of corn, is suspected to be a cause of human esophageal cancer. FB1 is hepatotoxic and hepatocarcinogenic in rats, and although the mechanisms involved have not been clarified, the latter is associated with a weak initiating activity. The effects of FB1 on the activity of protein serine/threonine phosphatases (PPs) (PP1, PP2A, PP2B, PP2C and PP5/T/K/H) were investigated in the present study. Inhibition of dephosphorylation was noted for all five PPs with IC50 values of 80 microM-3000 microM. Among the five PPs examined, PP5 was most sensitive with an IC50 of 80 microM. This concentration is comparable to that estimated to be reached in the rat body by feeding FB1 to obtain hepatic tumors. Inhibition of PP5 could thus play important roles in the toxicity and carcinogenic action of FB1.

Animals↗

Validation of the American Spinal Injury Association (ASIA) motor score and the National Acute Spinal Cord Injury Study (NASCIS) motor score.

STUDY DESIGN: In this study the motor scores of 62 consecutive acute spinal cord-injured patients were retrospectively reviewed. OBJECTIVE: The reliability of the American Spinal Injury Association and National Acute Spinal Cord Injury Study motor scores, compared with the conventional motor scores, was retrospectively assessed. SUMMARY OF BACKGROUND DATA: The reliability of the American Spinal Injury Association and National Acute Spinal Cord Injury Study scores has not as yet been confirmed. METHODS: Sixty-two consecutive adult patients admitted within 7 days of acute spinal cord injury between April, 1983, and September, 1992, were evaluated. The motor deficit percentage and the motor recovery percentage of each of the American Spinal Injury Association and the National Acute Spinal Cord Injury Study motor scores were compared with those of the conventional motor score. From the initial and final motor score, the motor deficit percentage and motor recovery percentage were calculated. There were 38 patients with cervical and thoracic lesions, 12 patients with dorso-lumbar lesions, and 12 patients with lower lumbar lesions. The average follow-up period was 41 months. RESULTS: Both the American Spinal Injury Association motor score and the National Acute Spinal Cord Injury Study motor score were representative of the conventional motor score for the evaluation of the motor deficit percentage and the motor recovery percentage in all levels (P < 0.0001). The differences in all correlation coefficients between the American Spinal Injury Association motor score and the National Acute Spinal Cord Injury Study motor score were not statistically significant in all levels and in every group. CONCLUSIONS: The American Spinal Injury Association and National Acute Spinal Cord Injury Study motor scores can both be used for the neurological quantification of motor deficit and motor recovery.

Adolescent↗

Hepatocyte growth factor induces transglutaminase activity that negatively regulates the growth signal in primary cultured hepatocytes.

Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 117 nM hepatocyte growth factor (HGF). In the same manner, putrescine incorporation into proteins of cells occurred in HGF-treated cells but did not in those pretreated with monodansylcadaverine (MDC), a TGase inhibitor, even in the presence of HGF. These results suggest that HGF-induced TGase was active and catalyzed some cross-linkage reaction. Cycloheximide completely blocked the increase in TGase activity induced by HGF, suggesting that HGF stimulated de novo synthesis of TGase within 6 h. Both [35S]methionine incorporation and Northern blotting analyses supported this possibility. Pretreatment of cells with MDC additionally increased HGF-induced DNA synthesis and the ratio of cells in S-phase. Similarly, TGase antisense oligonucleotide inhibited de novo synthesis of TGase, resulting in increase in the ratio of S-phase cells in the presence of HGF. Analyses of cross-linking of HGF to the receptor indicated that the antisense oligonucleotide inhibited the downregulation of HGF receptor subsequent to HGF-addition. These results provide the first evidence for inducibility of de novo synthesis of TGase by HGF and suggest that TGase negatively regulates the growth signal of HGF through the downregulation of receptor.

Animals↗

Effects of exogenous transforming growth factor-beta 1 on spinal cord injury in rats.

This study was undertaken to examine the effect of transforming growth factor-beta 1 (TGF-beta 1) administered into the subarachnoid space after spinal cord injury (SCI) on the increased production of inducible-nitric oxide synthase (i-NOS) in the injured spinal cord in rats. The expression of i-NOS mRNA after SCI was remarkably down-regulated by TGF-beta 1 in vivo. Rats treated with TGF-beta 1 showed a better outcome regarding hindlimb motor dysfunction in the first 5 days after injury compared to the saline-treated rats. However, the final outcome was not better and fibrous scar formation in the injured spinal cord was more evident, which was demonstrated as increased immunoreactivity of fibronectin in the later stage after SCI. These results provide evidence of both positive and negative contributions of TGF-beta 1 to the pathology associated with SCI.

Animals↗

Transglutaminase induced by epidermal growth factor negatively regulates the growth signal in primary cultured hepatocytes.

Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 17 nM epidermal growth factor (EGF). In the same manner, putrescine incorporation into the proteins of cells occurred in EGF-treated cells, but not in those pretreated with monodansylcadaverine (MDC), a TGase inhibitor, even in the presence of EGF. These results suggest that EGF-induced TGase was active and catalysed some cross-linkage reaction. Cycloheximide completely blocked the increase in TGase activity induced by EGF, suggesting that EGF stimulated de novo synthesis of TGase within 6 h. Furthermore, Northern blotting analysis indicated that EGF increased the expression of TGase mRNA. Pretreatment of cells with MDC additionally increased EGF-induced DNA-synthesis and the ratio of cells in S-phase. TGase antisense oligonucleotide inhibited de novo synthesis of TGase, resulting in increases in the ratios of S- and G2/M-phase cells in the presence of EGF. This effect was the result of inhibition of EGF-induced down-regulation of high-affinity receptor expression. These results suggest that the EGF-induced increase in TGase activity is a negative regulator of a growth signal in rat hepatocytes.

Animals↗

Investigation of the relationship between regression of hypertensive cardiac hypertrophy and improvement of cardiac sympathetic nervous dysfunction using iodine-123 metaiodobenzylguanidine myocardial imaging.

Although many theories exist on the subject, the mechanisms responsible for a reduction of hypertensive cardiac hypertrophy in response to antihypertensive therapy are still unclear. In order to investigate the relationship between regression of hypertensive cardiac hypertrophy and cardiac nervous function, we studied ten patients with untreated essential hypertension (six men and four women, 62+/-12 years old). Both echocardiography and iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging were performed before and after antihypertensive therapy. Left ventricular mass (LVM) was significantly reduced in conjunction with the reduction of blood pressure following treatment. MIBG myocardial images showed that the heart-to-mediastinum activity ratio (H/M) was significantly increased while the washout ratio was significantly decreased. Patients were divided into two groups according to the ratio of the LVM values before and after therapy (LVM ratio). Patients with an LVM ratio of less than 0.75 were classified as group A and those with values higher than 0.75 as group B. Neither the change in blood pressure nor the length of treatment was significantly different between these two groups. On the other hand, both the increase in H/M and the decrease in the washout ratio were significantly greater in group A than in group B. These results indicate that an improvement in cardiac sympathetic nervous function may be related to the regression of hypertensive cardiac hypertrophy. Increasing the subject base in these studies and a more precise analysis of the relevance of the data obtained from MIBG myocardial images are recommended to clarify how changes in cardiac sympathetic nervous function relate to the regression of hypertensive cardiac hypertrophy.

3-Iodobenzylguanidine↗

Roles of nitric oxide in compression injury of rat spinal cord.

Nitric oxide (NO) was measured directly after spinal cord injury (SCI) in rats by an ESR spin-trapping technique using Fe2+ and diethyldithiocarbamate (DETC). The levels of NO and lipid peroxides expressed as thiobarbituric acid reactive substances (TBARS) were increased by SCI in the injured region and the adjacent central region. Pretreatment with 30 mg/kg of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO synthase, accelerated increases of the TBARS level and myeloperoxidase (MPO) activity in the injured tissue and caused deterioration of hind limb motor function after SCI, suggesting that NO formation by constitutive NO synthase (c-NOS) has a protective effect against cellular damage resulting from ischemia-reperfusion after SCI. Though c-NOS mRNA expression was not altered after SCI, inducible NO synthase (i-NOS) mRNA expression increased to a maximum of 24 h after SCI with progress of motor dysfunction. Intravenous injection of L-NAME (0.1 mg/kg) 6, 24, 48, and 72 h after SCI reduced the motor disturbance. These results indicate that NO induced by i-NOS may be neurotoxic in the subacute phase after SCI.

Animals↗

Effect of dietary vitamin C on compression injury of the spinal cord in a rat mutant unable to synthesize ascorbic acid and its correlation with that of vitamin E.

The roles of vitamin C on secondary pathological changes after spinal cord injury were investigated by evaluating the effects of dietary vitamin C on experimental spinal cord injury in a mutant strain of Wistar rats unable to synthesize ascorbic acid (ODS rats). Two groups of ODS rats were given vitamin C-deficient or vitamin C-supplemented diet for 1 week before injury. Motor disturbance induced by spinal cord injury was found to be greater in the vitamin C-deficient group. Histologically, the area of bleeding in the spinal cord was also greater in the vitamin C-deficient group. The levels of ascorbic acid and alpha-tocopherol in the spinal cord tissue and serum decreased during and after compression injury of the spinal cord. The decrease of alpha-tocopherol was similar in the two groups. However, the decrease of ascorbic acid was greater in the vitamin C-supplemented group. These results indicated that their protective effects against spinal cord injury are through scavenging water-soluble free radicals by vitamin C and lipid-soluble by vitamin E, and the effects of these vitamins were suggested to be independent.

Animals↗

Sports-related spinal cord injury in Japan (from the nationwide spinal cord injury registry between 1990 and 1992).

The Injury Prevention Committee of the Japan Medical Society of Paraplegia (JMSoP) conducted a nationwide epidemiological survey on spinal cord injury (SCI) using postal questionnaires for 3 years periods from 1990 to 1992, and the annual incidence of the spinal cord injury was estimated as 40.2 per million. From this registry, we investigated SCI related to sports activities. In 3 years, 528 patients were registered and 374 of them had neurological deficits. The incidence was 1.95 per million per annum. Mean age at injury was 28.5 years (10-77), and 88.1% of the patients were males. Diving was the commonest cause of SCI (21.6%), which was followed by skiing (13.4%), football including rugby, American football and soccer (12.7%), sky sports (7.0%), judo (6.8%) and gymnastics (6.6%). Mean age at injury was higher than 30 years in skiing (38.6 years) and sky sports (38.2 years). Cervical injury was predominant in all but sky sports and accounted for 83.5% of SCI. Motor complete paralysis was reported in 35.0% of the patients. Bony injury was observed in 55.9% of the patients; most of the patients who sustained the SCI in diving and sky sports had bony injury, and no bony injury was detected in more than a half of the patients who sustained injuries in skiing, judo or gymnastics. Although the percentage of sports-related SCI was small in the present study as compared to the data from previous reports, it is not difficult to imagine the increase in the number of sports-related SCI. We have launched an injury prevention campaign and are planning to conduct a similar study in future to evaluate the effect of the campaign as well as the changes in the incidence and pattern of SCI.

Adolescent↗