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Biomedical subjects

M Nagashima

Publications and source records attributed to M Nagashima.

At least 181 records · Page 10Linked to original sources
PubMed1993

Bone marrow-derived dendritic epidermal T cells express T cell receptor-alpha beta/CD3 and CD8. Evidence for their extrathymic maturation.

The majority of murine Thy-1+ dendritic epidermal T cells (DETC) express virtually identical TCR encoded by V gamma 5 and V delta 1 genes and are derived from early fetal thymic precursors. However, not consistent with this notion is an early finding that DETC arise continuously from bone marrow (BM) precursors by a thymus-independent mechanism. To address this issue, donor-type DETC were characterized in lethally irradiated mice that were reconstituted by Thy-1-disparate BM cells with or without a thymus. The BM-derived DETC, unlike their normal TCR-gamma delta counterparts, were found to express the TCR-alpha beta/CD3 complex and CD8, and their migration to the epidermis dermis occurred independently of the thymus. The numbers of the BM-derived DETC increased with time and reached a plateau 6 mo after BM transfer, at which time the TCR-alpha beta/CD3 complex was expressed on a small fraction of the DETC in athymic BM chimeras. Although no further increase in the number was observed at later times, at 1 yr after transfer most of the BM-derived DETC came to express the TCR-alpha beta/CD3 complex in the absence of thymic influence. By contrast, most of BM-derived T cells in other lymphoid organs from athymic BM chimeras still failed to express the TCR-alpha beta/CD3 complex even at 1 yr after transfer. These results suggest that extrathymic differentiation of BM-derived DETC could occur with the epidermal microenvironment.

Animals↗
PubMed1993

The short loop between epidermal growth factor-like domains 4 and 5 is critical for human thrombomodulin function.

Thrombomodulin (TM) is a cofactor for activation of protein C by thrombin. We showed that 80-90% of this cofactor activity is lost by oxidation of Met388, located within the short interdomain loop between epidermal growth factor-like domains 4 and 5 (Glaser, C. B., Morser, J., Clarke, J. H., Blasko, E., McLean, K., Kuhn, I., Chang, R.-J., Lin, J.-H., Vilander, L., Andrews, W. H., and Light, D. R. (1992) J. Clin. Invest. 90, 2565-2573). For each of the 3 amino acids of the loop, site-specific mutants are described in which, 1) all possible single amino acid substitutions are made, 2) deletions are made, or 3) alanine is inserted adjacent to each residue of the loop. Most substitutions within the loop (38/57) result in a > 50% decrease in cofactor activity, while changes in the length of this region result in > 90% loss of activity. Only the Met388-->Leu mutant has higher cofactor activity (2-fold) than wild-type TM. A number of soluble and full-length TM analogs with the Met388-->Leu substitution are improved thrombin cofactors, whether produced in bacteria, insect, or mammalian cells. Detailed kinetic analysis of a soluble TM analog consisting of the six EGF-like domains secreted from insect cells shows that the enhanced activity of the Met388-->Leu mutant results from an increased catalytic efficiency (kcat/Km). This enhancement is maximal at physiological concentrations of calcium. The loss of activity following Met388 oxidation in the wild-type protein is the result of both decreased binding to thrombin (Kd effect) and a decreased interaction of the TM.thrombin complex with protein C (Km effect). We demonstrate the critical role of this interdomain loop in the biological anticoagulant properties of TM.

Amino Acid Sequence↗
PubMed1993

Alanine-scanning mutagenesis of the epidermal growth factor-like domains of human thrombomodulin identifies critical residues for its cofactor activity.

Thrombomodulin (TM) is an endothelial cell surface-bound cofactor in thrombin-dependent formation of activated protein C, a potent anticoagulant. Cofactor activity has been localized to the carboxyl-terminal half of the six epidermal growth factor-like (EGF) domains of TM (TME). To identify residues in TME that are critical for activity, 77 alanine point mutants were made between Cys-333 and Cys-462 by site-directed mutagenesis (all residues except Ala, Cys, Gly, and Pro). Mutants were expressed in Escherichia coli and cofactor activity measured directly in periplasmic extracts obtained by osmotic shock. Critical residues were defined as those which when mutated had less than 25% cofactor activity of a reference TME. Western blots of non-reduced samples confirmed that alanine substitutions did not significantly decrease expression levels or result in the formation of multimers. In EGF4, which is essential for protein C activation by the thrombin-TM complex, critical residues were: Asp-349, Glu-357, Tyr-358, and Phe-376. In EGF5-EGF6, critical residues within a proposed acidic thrombin-binding region were: Glu-408, Tyr-413, Ile-414, Leu-415, Asp-416, Asp-417, Asp-423, Ile-424, Asp-425, and Glu-426. A potential Ca(2+)-binding site, which is comprised of residues Asp-423, Asp-425, Glu-426, Asn-439, Leu-440, and Phe-444, was also identified and overlaps the thrombin-binding region. Asp-461, in the C-loop of EGF6 previously shown to be critical for thrombin binding, was also critical. Asp-398, Asp-400, Asn-402, and Asn-429 in EGF5 were also critical. Thus, rapid alanine-scanning mutagenesis of TME has identified 22 critical residues in the region comprising EGF4-6, which is essential for thrombin binding and protein C activation by the thrombin-TM complex.

Alanine↗
PubMed1993

Unruptured aneurysms associated with ischaemic cerebrovascular diseases. Surgical indication.

Out of 3435 patients with ischaemic cerebrovascular disease 2540 cases were investigated using cerebral angiography. In 127 of them (5%) aneurysms were found, but without clinical evidence of subarachnoid haemorrhage (SAH). 45 cases were operated upon and 82 were treated conservatively. Five of these 82 cases (6%) suffered from SAH 3 months to 10 years (mean interval 5.6 years) after the angiographic diagnosis. Four of these 5 patients with SAH died. Among the 45 surgical cases follow-up was uneventful in 29 (64%). The other 16 cases postoperatively showed neurological deterioration (36%), which was transient in 6 but with only minor improvement in 10. Of these 10 cases 2 died from cerebral infarction related to intra-operative temporary vascular occlusion respectively myocardial infarction. Thus surgical mortality was 4% and permanent morbidity 18%. Causes of postoperative neurological deterioration were partly related to general arteriosclerotic changes and special fragility of the ischaemic brain, and partly to operative technique (excessive brain retraction, damage to cortical veins, occlusion of major vessels or damage to perforators, temporary artery occlusion). Apparently in cases with ischaemic cerebrovascular diseases operative procedures, which in other cases as a rule are well tolerated, may produce harmful effects. Therefore, in these cases, the indication for operative treatment of so far silent aneurysms should be restricted to patients who are in good general condition with longer life expectancy as far as the vascular disease is concerned, and without major neurological deficit. Furthermore, the operative technique should be especially gentle and atraumatic.

Adult↗
PubMed1993

Biofeedback therapy for fecal incontinence after surgery for anorectal malformations: preliminary results.

Eight patients with fecal incontinence after surgery for anorectal malformations received one to four sessions of biofeedback therapy. The physiologic status of the anorectum before and after biofeedback therapy was investigated by anorectal manometry and electromyography of the external sphincter. The effectiveness of biofeedback treatment and the indications for its use in patients with fecal incontinence were investigated. Three of the four patients responded well to biofeedback therapy following three or four training sessions. However, in the other five patients who had only one or two sessions, a good response to the therapy was not obtained. Anorectal manometry and electromyography recordings of the external sphincter showed that biofeedback therapy improved voluntary sphincter function. The three good responders had an adequate and resting pressure both before and after biofeedback therapy and had good electrical activity of the external sphincter after therapy. In the presence of adequate resting and pressure, biofeedback therapy should be attempted for the treatment of fecal incontinence after correction of anorectal malformations before resorting to further surgical intervention. However, biofeedback therapy may not be suitable if the sphincters are markedly hypoplastic, or do not surround the anal canal after an inappropriate pull-through operation.

Anal Canal↗
PubMed1993

Is sustained production of tumor necrosis factor-alpha relevant to the development of pustular psoriasis?

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as one of the critical mediators of psoriasis. Evidence for an important role on the progression of the disease is increasing, while recent clinical studies have suggested its beneficial role in the disease. Based on the results of our sequential analysis of the serum cytokine levels in a patient with pustular psoriasis, we speculate that immunologic effects of constitutive local release of TNF-alpha may be quite different from those of its systemic injection.

Granulocyte-Macrophage Colony-Stimulating Factor↗
PubMed1993

Investigation of clinical characteristics of ventricular extrasystole in children--using two dimensional RR interval plotting method.

Eighty-three children were monitored by Holter electrocardiography for ventricular premature contraction (VPC), and the relationship between the preceding RR interval and the coupling interval was plotted using a two-dimensional RR interval plotting method. With this method, the slope (a) and standard deviation (SD) of the linear regression (Y = aX+b) were determined. These parameters were used to classify the patients into one of two types: a fixed type (SD < 40 msec, a < 0.2) and an unfixed type. The unfixed type was further divided into four subtypes, based on the plotted morphology: scattered, dependent, biphasic, and intermediate. The relationships between the VPC origin, organic heart disease, ventricular tachycardia (VT) and parasystole were investigated in the five types. The fixed and dependent types comprised significantly greater proportions of the subjects with VPC of right ventricular origin than of subjects with VPC of left ventricular origin (fixed: 31/59 right VPC vs 4/24 left VPC, p < 0.005; dependent: 13/59 vs 1/24, p < 0.05). On the other hand, comparatively very few subjects of the scattered type showed right VPC (4/59 vs 18/24, p < 0.005). Finally, the biphasic and intermediate types were distributed fairly equally among the subjects with VPCs of right and left ventricular origin (biphasic: 5/59 vs 0/24, p = 0.31, intermediate: 6/59 vs 1/24, p = 0.67). Organic heart disease was present in 13 subjects (15.7% of total subjects), seven of whom were of the fixed type with right ventricular origin (22.6% of subjects of this type). VT was observed in 34 subjects, but was rare in the scattered type (2/22 subject, 9.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

A patient with rheumatoid arthritis complicated by Sjögren's syndrome that was possibly caused by reactivation of Epstein-Barr virus.

A 24-year-old woman developed rheumatoid arthritis in 1986. Anti-SS-A antibody was negative, and Sjögren's syndrome was not associated with the disease. In July 1988 the patient developed pyrexia and cervical lymph node swelling. Infectious mononucleosis was suspected, and a previous contact with Epstein-Barr virus (EBV) was indicated. Pyrexia and cervical lymph node swelling occurred repeatedly and after this dry eyes and mouth also developed. In May 1990 the patient again developed pyrexia and cervical lymph node swelling, and she also had anti-SS-A antibodies (64x) and symptoms associated with Sjögren's syndrome. EBV antibody showed reactivation of EBV by the presence of viral capsid antigen-IgM antibody and a decrease in antibody titer against EBV-associated nuclear antigen. The clinical symptoms of repeated fever and cervical lymph node swelling, as well as the reactivation of EBV, suggest that EBV might have been a factor participated in the onset of Sjögren's syndrome in this patient.

Adult↗
PubMed1993

Eosinophilic pustular folliculitis (Ofuji's disease). Immunohistochemical analysis.

BACKGROUND: Eosinophilic pustular folliculitis is a distinctive dermatosis that was first described in Japan. Although the histopathologic feature of eosinophilic pustular folliculitis is characterized by follicular infiltrates with numerous eosinophils, its pathophysiology remains unclear. The lesional skin of five patients with eosinophilic pustular folliculitis was examined using several monoclonal antibodies including a variety of anti-leukocyte adhesion molecules: endothelial cell adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1, by means of immunohistochemical techniques. OBSERVATION: Intercellular adhesion molecule 1 expression by keratinocytes was observed on follicular epithelium, but not on epidermis. The migration of eosinophils and lymphocytes, which were intensely positive for antilymphocyte function-associated antigen 1, was limited to follicular epithelium. Endothelial cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression of vascular endothelium was more often observed around hair follicles. There was no reactivity for interleukin 8 in follicular epithelium. CONCLUSIONS: These findings may explain the selective migration of eosinophils and lymphocytes to the hair follicles in eosinophilic pustular folliculitis.

Adult↗
PubMed1993

[A successful repair of traumatic thoracic aortic injury and descending colon perforation at acute phase].

A 41-year-old man suffered from traffic accident was referred to us because of chest and back pain. The CT examination showed periaortic hematoma and aortography revealed aneurysmal formation at the distal site to the left subclavian artery. We repaired the aortic injury with prosthetic graft at the acute phase successfully. As the results of the conservative treatment of the traumatic aortic injury are poor, we recommend operation at the acute phase.

Accidents, Traffic↗
PubMed1993

[A successful removal of a left atrial floating ball thrombus after mitral valve replacement].

A floating ball thrombus after mitral valve replacement is very rare. A 48-year-old female with a left atrial floating ball thrombus after mitral valve replacement is presented. She had headache and dizziness on the 16th post-operative day. Echocardiography revealed a floating ball thrombus in the left atrium. The ball thrombus was removed successfully on the 5th day after detecting that. The principle of the treatment of the floating ball thrombus is to remove that promptly after the diagnosis is established. But in the case of complicating with fresh cerebral or cerebellar infarction, the timing of the surgery is controversial.

Cerebral Infarction↗
PubMed1993

[Safe and easy surgical atrial septectomy for congenital heart diseases].

Surgical atrial septectomy using a Kerrison clamp, which is used in neurosurgery, was done in four elder infants without extra-corporeal circulation. Two (6 and 4 months old) had an atresia of left atrio-ventricular valve with small atrial septal defect, one (8 months) had a transposition of great arteries with closing multiple ventricular septal defects, and one had a pure pulmonary atresia. A purse string suture was put on the right atrial appendage and the clamp in a closing position was inserted into the left atrium through the appendage and the atrial septum. The edge of the atrial septal defect and/or patent foramen ovale was hooked by pulling it slowly. It was closed strictly and pulled out together with a resected atrial specimen. This technique is safer and easier than the Blalock-Hanlon technique and atrial septectomy under extra-corporeal circulation for elder infants for whom balloon atrial septostomy is difficult to be done.

Cardiac Surgical Procedures↗
PubMed1993

[Case report of congenital bronchial cyst in the subsuperior segment of the right lung].

A fifty-five-year-old man revealed abnormal shadow on chest X-P. Congenital Bronchial Cyst (CBC) is believed to be caused by the abnormal budding process during the early development of the foregut and after born result in formation of noninfected cysts in the lung. In this case, CBC was lined by columnarciliated epithelium and contained cartilages and bronchial mucous glands in their wall. They were located along the tracheobronchial tree and cystgraphy presented dumbbell-like change of cysts that were seen during the development stage. These findings support the past reports radiographically that CBC may result from occlusion of the proximal side of bronchus during the early development by unknown mechanism.

Bronchogenic Cyst↗
PubMed1993

[A case of modified Fontan procedure for SLL single ventricular heart with bicaval total occlusion].

We successfully performed a modified Fontan procedure and bidirectional Glenn shunt for a 6-year-old boy with single ventricular heart (SLL). After the operation, the patient suffered from a severe pneumonia, so intravenous catheter had to be inserted for a long time. Post operative angiography revealed bicaval total occlusion. But, inspite of these several complications, this patient is doing well. We believe that if bilateral SVC without communication exist on such a candidate for the Fontan type procedure, LSVC should be anastomosed to PA. The bidirectional Glenn shunt will contribute to save a life of the patient when the systemic venous route was occluded. In addition, the anticoagulation therapy should be taken for the patients underwent the Fontan type procedure.

Child↗
PubMed1992

Structure-function studies of the epidermal growth factor domains of human thrombomodulin.

Structure-function relationships in the 6 epidermal growth factor-like domains of human thrombomodulin (TME, residues 227-462) were studied by deletion mutagenesis. Purified and characterised proteins were used for kinetic studies. Deletion of EGF1, EGF2 and residues 310-332 in EGF3 had no effect on thrombin binding (Kd) or on kcat/KM for protein C activation by the thrombin-thrombomodulin complex. Deletion of the rest of EGF3 and the interdomain loop between EGF3 and EGF4 had no effect on Kd but decreased kcat/KM to 10% of TME. Deletion of residues 447-462 of EGF6 had no effect on kcat/KM but increased Kd for thrombin approximately 6-fold. Thus, the region 333-350 in EGF3-4 is critical for protein C activation by the thrombin-thrombomodulin complex and the region 447-462 in EGF6 is critical for thrombin binding.

Base Sequence↗