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Biomedical subjects

S Katoh

Publications and source records attributed to S Katoh.

At least 19 recordsLinked to original sources

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

Glycosylation of CD44 negatively regulates its recognition of hyaluronan.

Although CD44 is expressed on a wide variety of cell types, few of them use it to recognize the ligand hyaluronan (HA). A glycosylation-defective clone of Chinese hamster ovary cells (Lec 8) bound HA, demonstrating that complete processing of glycoproteins with addition of a full complement of sialic acid is not required. On the contrary, subsequent findings revealed that complex sugars on CD44 can actually inhibit ligand recognition. Two subclones of wild-type Chinese hamster ovary cells with similar amounts of surface CD44 were isolated on the basis of HA binding and found to differ with respect to CD44 size as well as staining with fluorescent lectins. Treatment of the nonbinding clone with tunicamycin reduced the size of the protein and allowed the cells to recognize HA via CD44. This function was also induced by treatment with deglycosylating enzymes (either a mixture of endoglycosidase F and N-glycosidase F or neuraminidase alone). A possible role for glycosylation in regulation of adhesion was then sought with a series of normal and transformed murine cells. Disruption of glycosylation or treatment with deglycosylating enzymes did not induce ligand binding in an interleukin 7-dependent pre-B cell line, and splenic B cells also appeared to be in an inactive state. Some normal B cells acquired the ability to recognize HA after stimulation with lipopolysaccharide or interleukin 5 and had distinctive surface characteristics (loss of immunoglobulin D and acquisition of CD43). An additional subset of activated cells might have been in a transitional state, because the cells bound ligand after neuraminidase treatment. The ligand-binding ability of a purified CD44-immunoglobulin fusion protein dramatically increased after neuraminidase treatment. Thus, differential glycosylation of this molecule is sufficient to influence its recognition function. Cell adhesion involving HA can be regulated by multiple mechanisms, one of which involves variable glycosylation of CD44.

Animals

Purification of recombinant alpha-amylase by immunoaffinity chromatography with anti-peptide antibody.

Adsorption characteristics of an anti-peptide antibody, obtained by immunization of eight amino acids in the C-terminal region of chimeric alpha-amylase of rice alpha-amylase isozymes, were studied by use of the chimeric enzyme and the peptide used for immunization. This anti-peptide antibody adsorbed the enzyme, as well as the peptide antigen, with sufficient affinity for immunoaffinity purification and was used for purification of the enzyme secreted from yeast cells. Chimeric alpha-amylase was purified by immunoaffinity chromatography to high purity in one step from the fermentation broth. One-third of the secreted enzyme was not adsorbed by the column of anti-peptide antibody because of processing in the C-terminal region.

Amino Acid Sequence

Motor recovery of patients presenting with motor paralysis and sensory sparing following cervical spinal cord injuries.

We studied the neurological progress of 21 consecutive patients with cervical spinal cord injuries, presenting with sensory sparing but with complete motor paralysis below the level of their injury (Frankel B). All patients were admitted within 48 h of injury and treated conservatively with 6 weeks of bedrest and traction, followed by 6 weeks of bracing. The follow-up period was more than 1 year (49.6 months on average). Despite the initial absence of motor power in the lower limbs, seven patients recovered significant motor power and were able to walk. The preservation of pinprick sensation between the level of the injury and the sacral dermatomes was the best prognostic indicator for useful motor recovery with 75% of the patients regaining the ability to walk. This pattern of sensory sparing predicted a statistically significant better motor outcome than other patterns of sensory sparing. Although 50% of patients with no sacral sensation and/or with anal sensation on rectal examination recovered motor power, this recovery was functional in only one out of eight patients.

Adolescent

A nationwide epidemiological survey of spinal cord injuries in Japan from January 1990 to December 1992.

This survey of traumatic spinal cord injuries in Japan from January 1990 to December 1992 was carried out by a statistical method of the nationwide epidemiological study. The number of the registered patients during these 3 years was 9752 and the mean response rate of every of the 47 prefectures was 51.4%. The registered patients with neurological deficits (Frankel A-D) were 7471 and the annual spinal cord injury incidence was 40.2 per million. The ratio of cervical cord injuries to more caudal SCI was 3:1. The age distribution and the causes of spinal cord injuries are presented in detail. From the results of this study, the prevention campaign should be focused mainly on the following topics: sports and motorcycle accidents involving young people; traffic accidents involving adults; falling accidents involving aged people.

Accidents, Occupational

Influence of minor trauma to the neck on the neurological outcome in patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine.

The influence of minor trauma to the neck on the neurological outcome in patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine was evaluated retrospectively. Out of 118 patients treated in our clinic for cervical OPLL between 1976 and 1992, 27 had sustained minor trauma to the cervical spine. Of these 27 patients, 13 developed myelopathy, seven showed deterioration of preexisting myelopathy, and no neurological change was observed in seven patients. Regarding the relationship between the diameter of the residual spinal canal and the neurological outcome in these 27 patients, 18 out of the 19 patients with a narrow residual spinal canal (< 10 mm) developed neurological deterioration, whereas that occurred in only two of the eight patients with a wider spinal canal (> or = 10 mm). Although the severity of myelopathy and the transverse area of the spinal cord measured from T1-weighted magnetic resonance images, in patients who had sustained minor trauma was not statistically different from patients without trauma, neurological recovery after surgical treatment was poorer in the former group than in the latter. These results indicate that even indirect minor trauma to the neck can cause irreversible changes in the spinal cord if there is marked stenosis of the cervical spinal canal; such patients who are at risk, must be educated, and should be told to avoid even minor injuries at any cost.

Adult

Monoclonal antibodies to CD44 and their influence on hyaluronan recognition.

Antibodies to CD44 have been used to inhibit a variety of processes which include lymphohemopoiesis, lymphocyte migration, and tumor metastasis. Some, but not all, CD44-mediated functions derive from its ability to serve as a receptor for hyaluronan (HA). However, sites on CD44 that interact with either ligands or antibodies are poorly understood. Interspecies rat/mouse CD44 chimeras were used to analyze the specificity of 25 mAbs and to determine that they recognize at least seven epitopes. Amino acid substitutions that resulted in loss of antibody recognition were all located in the region of homology to other cartilage link family proteins. While at least five epitopes were eliminated by single amino acid replacements, multiple residues had to be changed to destroy binding by other antibodies. One antibody was sensitive to changes in any of three separate parts of the molecule and some antibodies to distinct epitopes cross-blocked each other. Certain antibodies had the ability to increase HA binding by lymphocytes but this did not correlate absolutely with antibody specificity and was only partially attributable to CD44 cross-linking. Antibodies that consistently blocked HA recognition were all sensitive to amino acid changes within a short stretch of CD44. Such blocking antibodies interacted with CD44 more strongly than ligand in competition experiments. One large group of antibodies blocked ligand binding, but only with a particular cell line. This detailed analysis adds to our understanding of functional domains within CD44 and requirements for antibodies to influence recognition of one ligand.

Amino Acid Sequence

Pulmonary arteriovenous fistula associated with unequal branching of the pulmonary artery system.

A 60-year-old woman was admitted to our hospital with shortness of breath and was diagnosed to have pulmonary arteriovenous fistula with unequal branching of the pulmonary artery system, as assessed by pulmonary angiography. The concomitant occurrence has not been reported previously. Although the etiology of these abnormalities is unknown, these abnormalities are considered to have occurred during an early stage of fetal development. The analysis of a concomitant occurrence of these abnormalities may be useful in elucidating the etiology of pulmonary arteriovenous fistula.

Arteriovenous Fistula

FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Japanese FK506 BMT Study Group.

A phase II study of the efficacy and safety of FK506, a new potent immunosuppressant, has been conducted in 49 patients with GVHD after allogeneic BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the study. FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg orally twice a day to those whose GVHD had become uncontrollable with cyclosporin and/or other immunosuppressants. The response to FK506 was evaluated in 13 patients with acute and 26 with chronic GVHD. A marked response was observed in 5 and a good response in 2 of 13 patients with acute GVHD. For those with chronic GVHD, the response was marked in 2 patients, good in 10 and poor in 8. The most common adverse effects were renal toxicity (53.1%), followed by nausea and vomiting (30.6%) and a feeding of warmth (18.4%). There was a correlation between renal toxicity and whole blood levels of FK506. The dose should be adjusted to keep a trough level between 15 and 25 ng/ml. FK506 is promising in the treatment of both acute and chronic GVHD, even if it is intractable with other immunosuppressants, and may be most effective if administered early in the course of GVHD.

Acute Disease

Lesions of the lumbar posterior end plate in children and adolescents. An MRI study.

We have reviewed 37 patients under the age of 18 years with lesions of the lumbar posterior end plate. All but one were active in sport, and most were seen because of low back pain. An abnormality was commonly found at the inferior rim of the body of L4 and at the superior rim of the sacrum. All adjacent intervertebral discs showed a decrease of signal intensity on the T2-weighted MRI. In 12 patients there was no interposed tissue at the posterior end-plate lesions. When disc material had migrated posteriorly none protruded beyond the posterior margin of the end plate, the dissociated portion of which was the main element compressing neural tissue. The posterior end-plate lesion should be regarded as a vertebral non-articular osteochondrosis.

Adolescent

Lumbar spondylolysis in children and adolescents.

We investigated 185 adolescents under the age of 19 years with spondylolysis. All but five were active in sport. The pars defect was classified into early, progressive and terminal stages. Of the 346 pars defects in 185 patients, 39.6% were early, 29.5% progressive and 30.9% in the terminal stages. Conservative management produced healing in 73.0% of the early, 38.5% of the progressive and none of the terminal defects. These results suggest that spondylolysis is caused by repetitive microtrauma during growth and can be successfully treated conservatively if treatment is started in the early stage. There was elongation of the pars interarticularis as the pars defect progressed, and this is likely to be a consequence of the defect rather than a contributing cause.

Adolescent

[Perioperative management of patients with Meigs syndrome].

We report our perioperative management of three cases of Meigs syndrome. The major pre-operative problems in Meigs syndrome are physical trouble caused by giant mass in peritoneal space, respiratory distress, and poor nutrition. These problems must be settled before the operation. The important points in the pre-operative management are 1) respiratory care employing the intermittent positive pressure breathing (IPPB) and the pleural effusion drainage, and 2) the correction of intravascular volume and the concentration of albumin and hemoglobin by transfusion of massive lactated Ringer solution and albumin solution and/or whole blood when they are necessary. During the operation, the epidural anesthesia under spontaneous breathing is the best method of anesthesia. According to circumstances, we adopt the intra-tracheal intubation with continuous positive airway pressure breathing (CPAP). We can generally deal with excessive bleeding by transfusion of lactated Ringer solution and plasma expander, during the first half of operation. By the end of the operation, however, the correction of the concentration of albumin and hemoglobin must be made by the fresh frozen plasma and blood transfusion. After the operation, we use epidural analgesia to control the postoperative pain. We have succeeded in the treatment of three cases of Meigs syndrome owing to our perioperative management as described above.

Analgesia, Epidural

The efficacy of indomethacin in the treatment of uremic pericarditis.

Uremic pericarditis is common in patients undergoing chronic hemodialysis and has been difficult to cure using conservative medical and surgical methods of treatment. Indomethacin therapy for uremic pericarditis has been reported infrequently. We present a case of uremic pericarditis in which indomethacin was particularly effective. The patient was a 45-year-old woman with thrombocytopenia due to Banti's syndrome and congestive heart failure with pericardial effusion. She had been undergoing hemodialysis for 3 years for chronic renal failure due to chronic glomerulonephritis. Uremic pericarditis was diagnosed based on serological laboratory results, aspirated pericardial fluid, and an echocardiogram. She was treated with oral doses of 25 mg t.i.d. indomethacin in addition to hemodialysis and extracorporeal ultrafiltration method. Pericardial effusion and left ventricular dysfunction disappeared after indomethacin therapy for 38 days. There are conflicting reports on the efficacy of indomethacin therapy in patients with uremic pericarditis. While indomethacin therapy was very effective in our case, there may be many causes of uremic pericarditis for which indomethacin may not be efficacious. Further investigations of indomethacin therapy for patients with uremic pericarditis are necessary to elucidate the therapeutic mechanism by which indomethacin acts.

Administration, Oral

[A case of hypertensive hypertrophy in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were observed after antihypertensive therapy].

A case of hypertensive hypertrophy is described in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were seen after 7 months of antihypertensive therapy. A 58-year-old man was diagnosed as having essential hypertension and hypertensive hypertrophy. The patient was treated with antihypertensive drugs and showed regression of left ventricular hypertrophy on electrocardiograms and echocardiograms. MIBG observations made before and after antihypertensive therapy showed increased heart-to-mediastinum activity ratio and decreased cardiac washout ratio. Despite the many theories addressing the mechanisms of regression of left ventricular hypertrophy, the process is still unclear. In the present case, the improvement of cardiac sympathetic nervous dysfunction might have been related to the regression of left ventricular hypertrophy because the abnormality in MIBG images improved. MIBG, therefore, may be helpful in clarifying the mechanisms of the regression of hypertensive hypertrophy.

3-Iodobenzylguanidine

Bone mineral density of the lumbar spine in patients with ossification of the posterior longitudinal ligament of the cervical spine.

Bone mineral density (BMD) of the lumbar spine in patients with ossification of the posterior longitudinal ligaments of the cervical spine (OPLL) was measured to elucidate the relation of spinal ossification with systemic hyperostotic condition. BMD in the lateral projection had a statistically significant correlation with that in the anteroposterior projection, and the former was considered to reflect the condition more accurately than was the latter, which may include the ossified spinal ligaments. BMD of patients with continuous and mixed types of OPLL was higher than that of those with the segmental type. Patients with OPLL and ossification of the other spinal ligaments had higher BMDs than did those without ossification. These results suggest that the BMD of the lumbar spine may reflect the systemic hyperostotic tendency and advancement of the ossification.

Absorptiometry, Photon