Evaluation of residual shunt flow of coronary artery fistulae by intra-operative transoesophageal echocardiography.
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Arterio-Arterial Fistula↗
Biomedical subjects
K Hosokawa
Publications and source records attributed to K Hosokawa.
Chemically modified thrombin and anhydrothrombin that differentiate macromolecular substrates of thrombin.
BACKGROUND: Thrombin is a primary inducer of thrombus formation by activations of coagulation cascade and platelet aggregation. Hitherto, several types of thrombin inhibitors have been developed for therapeutic purpose. OBJECTIVES: We prepared modified thrombin (M-thrombin) and modified anhydrothrombin (M-anhydrothrombin) by chemical modification of carboxyl groups of thrombin and anhydrothrombin, respectively, to present a new strategy for a potent antiplatelet-anticoagulant agent and new tools for investigation of thrombin functions. RESULTS: M-anhydrothrombin retained high affinity for factor VIII (FVIII), but demonstrated lower affinity than anhydrothrombin for fibrinogen and factor V (FV). Both M-anhydrothrombin and anhydrothrombin prolonged activated partial thromboplastin time (APTT) without affecting prothrombin time, and M-anhydrothrombin prolonged APTT much more than anhydrothrombin. M-anhydrothrombin also retained affinity for the recombinant extracellular domain peptide of protease-activated receptor 1 (PAR1). M-thrombin exhibited marginal clotting activity (4% of thrombin), but induced platelet aggregation in platelet-rich plasma without forming a fibrin clot, which was completely suppressed by anti-PAR1 antibody (ATAP2) and by M-anhydrothrombin, but not by anhydrothrombin. These results indicate that M-thrombin induced platelet aggregation through the activation of PAR1, and M-anhydrothrombin inhibited this process completely. In contrast, neither M-anhydrothrombin nor anhydrothrombin apparently inhibited thrombin-induced platelet aggregation. Only in the presence of the Gly-Pro-Arg-Pro (GPRP) peptide that inhibits polymerization of fibrin, M-anhydrothrombin completely inhibited thrombin-induced platelet aggregation. CONCLUSION: M-thrombin is PAR1-specific and M-anhydrothrombin is FVIII- and PAR1-specific derivatives, and thereby, are new tools as specific agonist and antagonist, respectively, of PAR1. Furthermore, M-anhydrothrombin may be an attractive model for development of a potent anticoagulant-antiplatelet agent.
Blood Coagulation↗
Endoscopic mucosal resection in the stomach using the insulated-tip needle-knife.
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Electrocoagulation↗
Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing.
BACKGROUND: The usefulness of bone marrow cells in accelerating wound healing has not been evaluated despite increasing evidence that bone marrow contains mesenchymal stem cells that have multipotentiality to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). OBJECTIVES: To determine the effects of bone marrow cells and occlusive dressings in promoting wound healing in rats. METHODS: We investigated by grafting, biopsy and immunohistochemistry whether various types of cells derived from green fluorescent protein (GFP)-transgenic rats would differentiate into wound component cells when administered topically on the wounds of rats. We also investigated whether topical application of bone marrow cells with an occlusive dressing would accelerate the healing of wounds with exposed bones, as measured by planimetry. RESULTS: GFP-labelled bone marrow cells contained multipotent stem cells that sufficiently differentiated into wound myofibroblasts presenting with alpha-smooth muscle actin in granulation tissue. Other types of cells, including myocytes, adipocytes, peripheral blood cells from buffy coat and dermal fibroblasts, did not express myofibroblast characteristics morphologically or immunohistochemically. Application of bone marrow cells and an occlusive dressing accelerated the repair of wounds with exposed bones, compared with an occlusive dressing only or with the topical administration of bone marrow cells plus a semidry to dry dressing. CONCLUSIONS: Our study indicates that bone marrow cells accelerate the healing of wounds at least in part through their differentiation into wound myofibroblasts. Thus, treatment of wounds with bone marrow cells and a supportive occlusive dressing is effective in promoting the formation of healthy granulation tissue and also for the preparation of an ideal wound bed.
Animals↗
Rapid healing of intractable diabetic foot ulcers with exposed bones following a novel therapy of exposing bone marrow cells and then grafting epidermal sheets.
BACKGROUND: Diabetic foot ulcers with exposed bones commonly result in amputation. OBJECTIVES: To determine whether exposure of bone marrow cells and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation. METHODS: Thirty-eight patients with chronic wounds caused by diabetes mellitus were enrolled in this study. Epidermal sheets obtained from suction blisters of each patient were grafted on to diabetic foot ulcers without exposed bones (n = 10) and were compared with the standard treatment of local wound care, debridement with a scalpel when indicated, bed rest and parenteral antibiotics (n = 8). In another group of patients, diabetic wounds with exposed bones were treated either with the standard procedure (n = 9) or with a newly developed experimental procedure (n = 11). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until fresh bleeding was observed from the exposed bone. The lesions were then immediately covered with an occlusive dressing, and finally the wound was covered with an epidermal graft of skin harvested from suction blisters. Patients in each group were matched with their counterparts by age, sex, wound size, wound infection and wound duration, to compare the time needed for total skin repair and rates of amputation. RESULTS: Epidermal grafting significantly accelerated the healing of diabetic foot ulcers (P = 0.042) without exposed bones, with site-specific differentiation. The newly developed combination therapy resulted in the healing of all diabetic ulcers with exposed bones without the occurrence of osteomyelitis or the necessity for amputation (P < 0.0001). CONCLUSIONS: Our study indicates that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation.
Adult↗
Epidermotropic metastatic malignant melanoma with a pedunculated appearance.
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Aged↗
Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency.
Significant reduction in bone mineral density (BMD) occurs in patients with Parkinson's disease (PD), correlating with immobilization and with vitamin D deficiency, and increasing the risk of hip fracture, especially in elderly women. As a biological indicator of compromised vitamin K status, an increased serum concentration of undercarboxylated osteocalcin (Oc) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women. We evaluated treatment with vitamin K(2) (menatetrenone; MK-4) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD. In a random and prospective study of PD patients, 60 received 45 mg of MK-4 daily for 12 months, and the remaining 60 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K(1) deficiencies, high serum levels of ionized calcium, and glutaminic residue (Glu) Oc, and low levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D], indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion. BMD in the second metacarpals increased by 0.9% in the treated group and decreased by 4.3% in the untreated group (p < 0.0001). Vitamin K(2) level increased by 259.8% in the treated group. Correspondingly, significant decreases in Glu Oc and calcium were observed in the treated group, in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures (eight at the hip and two at other sites) in the untreated group, and one hip fracture occurred among treated patients (p = 0.0082; odds ratio = 11.5). The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration, and it can also decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1,25-(OH)(2)D concentration.
Aged↗
Giant basal cell carcinoma affecting the lower abdominal, genital and bilateral inguinal regions.
We describe a giant basal cell carcinoma, measuring 40 cm x 20 cm, of the lower abdominal, genital and bilateral inguinal regions. The rectus abdominis muscle and the adductor magnus muscle were exposed centrally, and the penis and scrotum were completely destroyed. Reconstruction was performed with a fillet thigh flap, and an excellent result was obtained 1 year after surgery.
Abdominal Wall↗
Establishment of FSH-responsive cell lines by transfection of pre-ovulatory human granulosa cells with mutated p53 (p53val135) and Ha-ras genes.
Human granulosa cells were immortalized by transfection of the primary cells with a mutated p53 gene in combination with the Harvey-ras oncogene, yielding established cell lines designated HGP53. Here we report that forskolin, 8-Br-cAMP and FSH modulate cell growth and steroidogenesis in HGP53 cells. Low concentrations of 8-Br-cAMP or FSH stimulated cell proliferation, while higher doses attenuated cell proliferation. Progesterone production was already evident at an FSH concentration of 0.3 mIU/ml and was maximally stimulated (50-135-fold) at 50 mIU/ml of FSH. Expression levels of steroidogenic acute regulatory protein (StAR), adrenodoxin and cytochrome P450scc were enhanced 64-, 48- and 3.1-fold respectively by FSH stimulation. Dexamethasone enhanced FSH/cAMP-induced steroidogenesis and this effect involved a marked elevation in the intracellular level of adrenodoxin and P450scc, concomitantly with a marked decrease in StAR. Conversely, basic fibroblast growth factor attenuated FSH-stimulated progesterone production, and this effect involved reductions in adrenodoxin, P450scc and StAR levels. These data suggest that the rate of steroidogenesis may be determined by the ratio of StAR and P450scc, rather than by the level of each protein alone. Whereas FSH at a low dose slightly reduced apoptosis induced by serum withdrawal from HGP53 cells, higher doses enhanced it. Dexamethasone dramatically attenuated FSH- or forskolin-enhanced apoptosis. In conclusion, FSH-dependent mechanisms of differentiation, luteinization and apoptosis can be preserved in human granulosa cells immortalized by mutated p53. Moreover, this system lends itself to studies on cross-talk between the endocrine and paracrine factors that control these processes.
8-Bromo Cyclic Adenosine Monophosphate↗
Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples.
AIMS: The expression of human neuropsin (KLK8) mRNA in normal and pathological skin samples was analysed and the results compared with those for tissue plasminogen activator (tPA) mRNA. METHODS: Northern blot and in situ hybridisation analyses of KLK8 mRNA in normal and lesional skin of patients with cutaneous diseases were performed. RESULTS: A weak signal for KLK8 mRNA and no signal for tPA mRNA was seen in normal skin on northern blot analysis. Weak signals for KLK8 were localised to the superficial cells beneath the cornified layer in normal skin on in situ hybridisation. Psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma skin samples, which show severe hyperkeratosis, displayed a high density of KLK8 mRNA on northern and in situ hybridisation analyses. The signals were localised in granular and spinous layers of lesional skin in all hyperkeratic samples, including the area surrounding the horn pearls of squamous cell carcinoma. To examine the relation between mRNA expression and terminal differentiation, the expression of KLK8 mRNA was analysed in cell cultures. When keratinisation proceeded in high calcium medium, a correlative increase in the expression of KLK8 mRNA was observed. CONCLUSION: The results are consistent with a role for this protease in the terminal differentiation of keratinocytes.
Adult↗
Placenta previa of a succenturiate lobe: a report of two cases.
Previa of a succenturiate placenta is a rare condition. We report two cases of such lesions, which could not be detected by transabdominal ultrasound. When no cause of uterine bleeding is detected, previa of a posterior succenturiate lobe should be considered, and transvaginal ultrasound should be performed.
Abdominal Pain↗
Preparation of anhydrothrombin and characterization of its interaction with natural thrombin substrates.
Thrombin is a serine proteinase that plays a key role in thrombosis and haemostasis through its interaction with several coagulation factors. Anhydrothrombin was prepared from PMSF-inactivated thrombin under alkaline conditions, and the folded anhydrothrombin was successfully recovered after dialysis in the presence of glycerol. Anhydro-derivatives of factor Xa, factor VIIa and activated protein C could also be prepared essentially by the same procedure. Anhydrothrombin retained affinity for various natural substrates of thrombin, including fibrinogen, factor VIII, factor XIII and protein C. In addition, these proteins were bound to anhydrothrombin-agarose in a reversible manner. The K(d) values for factor VIII, fibrinogen, factor XIII and protein C were 1.2x10(-8), 4.4x10(-8), 2.8x10(-7) and 8.1x10(-5) M, respectively. Thus thrombin substrates known to interact with the exosite I of thrombin demonstrated high affinity for anhydrothrombin. Furthermore, in the presence of Na+, substantial enhancement of the association rate constant (k(ass)) was observed for interactions of fibrinogen and factor VIII with anhydrothrombin. These results suggest that anhydrothrombin is useful in the purification of thrombin substrate proteins as well as in the investigation of detailed interactions between thrombin and these substrates in their activation or degradation processes.
Chromatography, Affinity↗
Circulating factor VIII immune complexes in patients with type 2 acquired hemophilia A and protection from activated protein C-mediated proteolysis.
Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII antigen despite having low levels of FVIII activity were studied. The antibodies reacted exclusively with the light chain of FVIII but not with the C2 domain, and their epitopes were therefore ascribed to the regions in the A3-C1 domains. Heavy and light chains of FVIII were detected in plasma-derived immune complexes extracted by using protein G Sepharose. Direct binding assays using anhydro-activated protein C (anhydro-APC), a catalytically inactive derivative of activated protein C (APC) in which the active-site serine is converted to dehydroalanine, were used to examine the relation between immune complexes and APC. The intact FVIII, 80-kd light chain, and 72-kd light chain bound in a dose-dependent manner to anhydro-APC, with K(d) values of 580, 540, and 310 nM, respectively, whereas no appreciable binding was detected for the heavy chain. The 3 autoantibodies blocked FVIII binding to anhydro-APC by approximately 80% and consequently inhibited APC-induced FVIII proteolytic inactivation. These antibodies also bound to a synthetic peptide, His2009-Val2018, which contains the APC binding site. The findings suggest that binding of type 2 autoantibodies, recognizing residues His2009 to Val2018, protects FVIII from APC-mediated proteolysis and might contribute to the presence of FVIII immune complexes in the circulation.
Antigen-Antibody Complex↗
Mammary ductoscopy for diagnosis and treatment of intraductal lesions of the breast.
BACKGROUND: Mammary ductoscopy (mammoscopy) is an ideal diagnostic method for intraductal lesions. The usefulness of mammoscopy for intraductal lesions was evaluated. METHODS: Mammoscopy was performed in 315 cases with nipple discharge. The mammoscopic findings of 46 breast cancer cases (47 lesions) and 109 intraductal papilloma cases (119 lesions) were compared with pathological findings. RESULTS: Carcinoma was recognized by mammoscopy in 38 of 47 lesions (80.9%). Intraductal masses were detected by mammoscopy in 115 of 119 intraductal papilloma lesions. The shape of the mass was classified as hemispheric, papillary, or flat protrusion. The hemispheric and papillary shapes were most common in cases of intraductal papilloma and the flat protrusion type was most common in cases of carcinoma. The amount of material collected by intraductal biopsy under mammoscopic observation was smaller in carcinoma than in intraductal papilloma because the carcinoma lesions were usually located in peripheral duct-lobular units and had weak tissue cohesion compared with that of intraductal papilloma. Of 133 intraductal biopsies performed for 69 intraductal papillomas, 17 biopsies yielded material insufficient for diagnosis in. The effectiveness of treatment by intraductal biopsy was recognized in 38 of 46 intraductal papillomas in which clinical follow-up continued for more than two years (82.6%). The therapeutic results of biopsy were poor in cases of multiple intraductal masses in multiple duct-lobular units. CONCLUSIONS: Mammoscopy contributes not only the diagnosis in cases of nipple discharge, but is also of benefit in the treatment of intraductal papilloma.
Breast Neoplasms↗
Usefulness of stable HbA(1c) for supportive marker to diagnose diabetes mellitus in Japanese subjects.
To evaluate the adequacy and usefulness of the stable glycated hemoglobin (HbA(1c)) value of 6.5% suggested by the Japan Diabetic Society in 1999 for supportive diagnostic marker of diabetes, we assessed the sensitivity and specificity of an HbA(1c) value of 6.5% in patients who were newly diagnosed by the 75 g oral glucose tolerance test (75g-OGTT). A total of 866 Japanese subjects underwent the 75g-OGTT and HbA(1c) measurement (normal range: 4.3-5.8%). They were divided into three groups [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM)], using the WHO criteria, since no subject with impaired fasting glycemia (IFG) was observed. The cut-off value of HbA(1c) separating DM from NGT or DM from IGT on cumulative distribution curve analysis was 5.9% (sensitivity 0.76 and specificity 0.86) and 5.9% (sensitivity 0.76 and specificity 0.77), respectively. The sensitivity of an HbA(1c) of 6.5% for separation of DM from NGT or IGT by the same analysis was 0.49 and 0.49, respectively. Similarly, the specificity for separation of DM from NGT or IGT was 0.98 and 0.98, respectively. These results mean that 49% of diabetic subjects show an HbA(1c)> or =6.5%, and 51% have an HbA(1c) less than 6.5%, while only 2% of NGT and IGT subjects have an HbA(1c)> or =6.5%, and 98% have a value less than 6.5%. Therefore, the sensitivity of an HbA(1c) value of 6.5% in separating DM from NGT or IGT is low, and thus 6.5% is too high value to use when screening for diabetes. However, the specificity is very high, so an HbA(1c) of 6.5% is a useful supportive marker to diagnose diabetes.
Adult↗
Protocol to prevent shoulder-hand syndrome after stroke.
OBJECTIVE: To determine the effectiveness of a protocol designed to restrict passive movement of affected upper extremity on the incidence of shoulder-hand syndrome (SHS) after stroke. DESIGN: Before-and-after trial: follow-up duration of subject group and historical control group 231.6 and 257.2 days, respectively. SETTING: Rehabilitation medicine department in a hospital in Japan. PARTICIPANTS SUBJECTS: 81 stroke patients treated with the protocol from 1994 to 1996 who were followed for at least 4 months from the onset of stroke; controls: 71 stroke patients treated without the protocol from 1991 to 1994 who were followed for same length of time. INTERVENTION: Use of a set protocol for controlled passive movement by trained therapists and restriction of passive movement by the patients for 4 months after stroke. The SHS criterion used to detect early signs of SHS has not yet been validated. Corticosteroids were given to all subjects diagnosed with SHS. MAIN OUTCOME MEASURES: Swelling index, SHS diagnostic criteria applied in physical exam, Brunnstrom stage, and sensory disturbance evaluations. RESULT: The incidence of SHS in the subject group was 18.5% (n = 15), whereas the incidence of SHS in the control group was 32.4% (n = 23). The difference between the 2 groups was statistically significant (chi(2) = 3.885, p < .05). CONCLUSION: The protocol helped to prevent development of SHS.
Chi-Square Distribution↗
Multiple pilomatrixomata without myotonic dystrophy.
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Cheek↗
New endoscopic treatment for intramucosal gastric tumors using an insulated-tip diathermic knife.
BACKGROUND AND STUDY AIMS: For one-piece resection the conventional technique of endoscopic mucosal resection (EMR) is limited to gastric mucosal tumors of 10 mm or less in size. In this retrospective study, we investigated the efficacy and complications associated with a new EMR method, using an insulated-tip diathermic knife (IT-EMR). PATIENTS AND METHODS: In a total of 41 patients gastric mucosal tumors were resected using IT-EMR. RESULTS: One-piece resection rates were 82% (14/17) for lesions of 10 mm or less, 75% (12/16) for those between 11 and 20 mm, and 14% (1/7) for those of over 20 mm. Complication rates for severe bleeding and perforation were 22% and 5%, respectively. With a median follow-up period of 32 months, no recurrence was observed after these procedures. CONCLUSIONS: Compared with conventional EMR, this new method may have significant benefits, particularly regarding one-piece resection of lesions between 11 and 20 mm in size, and may also have a lower recurrence rate.
Adenocarcinoma↗