Biomedical subjects
Publications and source records attributed to A Fukui.
The Ran gene family encodes small GTP binding proteins that are associated with a variety of nuclear processes. We isolated a Xenopus Ran cDNA and analyzed the pattern of expression of this gene during embryogenesis. Ran is expressed maternally and later in the CNS, neural crest, mesenchyme, eyes, and otic vesicles. However, expression is not detected in the somites or the notochord.
Wnt signaling plays an important role in axis formation in early vertebrate development. Axin is one Wnt signaling regulator that inhibits this pathway. The effects of the injection of mRNA of several rat Axin (rAxin) mutants on axis formation in Xenopus embryos were examined. It was found that rAxin mutants containing only a regulation of G-protein signaling (RGS) domain fragment or with deletion of the RGS domain induced axis formation. Because the RGS domain is a major adenomatous polyposis coli gene product (APC)-binding domain, APC association with glycogen synthase kinase 3beta (GSK3beta) on the Axin molecule may be important in inhibition of axis formation. The ventralizing activities of wild-type rAxin and a mutant in which the Dishevelled and Axin (DIX) domain was deleted (deltaDIX mutant) were examined. Histological examination and gene expression revealed that the ventralizing activity of the deltaDIX mutant was weaker than that of wild-type rAxin. This finding suggests that the C-terminus of rAxin contributes to the inhibition of Wnt signaling in Xenopus embryos. Furthermore, an rAxin mutant that contained both the RGS and GSK3beta-binding domains affected both the dorsal and ventral sides of blastomeres, mediated ectodermal fate and induced expansion of notochord and/or endoderm, but did not induce axis formation.
The authors performed anastomoses of small vessels with the Nd-YAG laser, comparing these with conventional suture anastomoses. Some arteries were sutured with 10-0 nylon with about eight suture sites, and others were held by stay sutures at three points with laser irradiation performed between them. Two surgeons performed the anastomoses in the same way. The first was well-trained and experienced, and the second was technically inexperienced. The authors evaluated clamping time, patency rate, and endoscopic and histologic findings. The patency rate of the first surgeon was 100 percent (30/30) in the suture anastomoses and was 97 percent (29/30) in the laser anastomoses. For the second surgeon, the rates were 60 percent (18/30) in the suture group and 80 percent (24/30) in the laser group. On histologic examination, the suture group showed inflammatory cells around the suture site at the fourth week after the operation. In the laser group, an inflammatory reaction around the suture material was observed, but the other areas recovered. For the experienced surgeon, the patency rate and clamping time of the laser anastomosis provided no statistically significant difference to those of the suture anastomosis. On the other hand, for the inexperienced surgeon, the patency rate of the laser anastomosis was superior to that of the suture anastomosis, and the clamping time of the laser anastomosis was shorter than that of the suture anastomosis. Therefore, the authors concluded that the Nd-YAG laser anastomosis is useful for small vessels.
The authors treated 14 patients (13 men and one woman), using a sensate radial forearm flap. Their ages at operation ranged from 27 to 67 years (mean: 52 years). Preoperative conditions were amputations in 10 cases, degloving injury in three, and crush injury in one. Reconstructive sites involved the thumb in nine cases, the mitten-like hand in two, the index finger in one, the ring and small finger in one, and the palm in one. In all cases, the radial forearm flap, including the lateral antebrachial cutaneous nerve, was harvested. Sensory evaluation was performed using the moving two-point discrimination test (m-2PD). Sensation in the mid-palmar area of 50 forearms was examined in 25 healthy adult volunteers as a control group. Follow-up periods ranged from 12 to 87 months (mean: 39.6 months). The mean m-2PD of the 14 sensory flaps was 13.2 mm, and the mean of 50 forearms in the control group was 18.08 mm. A statistically significant difference was demonstrated between the sensory flaps and the 50 forearms of the control group. The mean m-2PD was much more sensitive in the innervated radial forearm flaps than in the donor forearm. The results suggested that sensory return in the innervated flaps is influenced not by the donor nerve in the flaps, but by the recipient digital nerve.
A reverse-flow island flap from the hypothenar eminence of the hand was applied in 11 patients to treat palmar skin defects, amputation injuries, or flexion contractures of the little finger. There were three female and eight male patients, and their ages at the time of surgery averaged 46 years. A 3 x 1.5 to 5 X 2 cm fasciocutaneous flap from the ulnar aspect of the hypothenar eminence, which was located over the abductor digiti minimi muscle, was designed and transferred in a retrograde fashion to cover the skin and soft-tissue defects of the little finger. The flap was based on the ulnar palmar digital artery of the little finger and in three patients was sensated by the dorsal branch of the ulnar nerve or by branches of the ulnar palmar digital nerve of the little finger. Follow-up periods averaged 42 months. The postoperative course was uneventful for all patients, and all of the flaps survived without complications. The donor site was closed primarily in all cases, and no patient complained of significant donor-site problems. Satisfactory sensory reinnervation was achieved in patients who underwent sensory flap transfer, as indicated by 5 mm of moving two-point discrimination. A reverse island flap from the hypothenar eminence is easily elevated, contains durable fasciocutaneous structures, and has a good color and texture match to the finger pulp. This flap is a good alternative for reconstruction of palmar skin and soft-tissue defects of the little finger.
The asymmetric distribution of cellular components is an important clue for understanding cell fate decision during embryonic patterning and cell functioning after differentiation. In C. elegans embryos, PAR-3 and aPKC form a complex that colocalizes to the anterior periphery of the one-cell embryo, and are indispensable for anterior-posterior polarity that is formed prior to asymmetric cell division. In mammals, ASIP (PAR-3 homologue) and aPKCgamma form a complex and colocalize to the epithelial tight junctions, which play critical roles in epithelial cell polarity. Although the mechanism by which PAR-3/ASIP and aPKC regulate cell polarization remains to be clarified, evolutionary conservation of the PAR-3/ASIP-aPKC complex suggests their general role in cell polarity organization. Here, we show the presence of the protein complex in Xenopus laevis. In epithelial cells, XASIP and XaPKC colocalize to the cell-cell contact region. To our surprise, they also colocalize to the animal hemisphere of mature oocytes, whereas they localize uniformly in immature oocytes. Moreover, hormonal stimulation of immature oocytes results in a change in the distribution of XaPKC 2-3 hours after the completion of germinal vesicle breakdown, which requires the kinase activity of aPKC. These results suggest that meiotic maturation induces the animal-vegetal asymmetry of aPKC.
Dobutamine (DOB) stress two-dimensional echocardiography is an established method for the detection of viable myocardium, but conventional assessment of wall motion is subjective. We measured quantitatively the left ventricular systolic velocities along the longitudinal axis by pulsed Doppler tissue imaging (DTI). In 30 patients with previous myocardial infarction, pulsed DTI focused on the infarct area was performed from an apical two- or four-chamber view before and during DOB (10 microg/kg/min) stress one day before coronary angioplasty. We calculated peak systolic velocity (S), regional pre-ejection period (PEP, the time interval from the onset of QRS to the onset of systolic wave) and regional ejection time (ET). Left ventriculography was obtained before and 3 months after coronary angioplasty to assess regional wall motion. Improvement of abnormal wall motion was observed in 19 patients (group P) but not in 11 (group N). Group P had significantly larger S and smaller PEP/ET than group N during DOB stress, although there were no significant differences in these indices between the groups at baseline. As a consequence, group P had a significantly larger percent change in S and a smaller percent change in PEP/ET than group N (164+/-39 vs 117+/-20% and 88+/-17 vs 116+/-29%, respectively, p < 0.01). It is suggested that the quantitative measurement of longitudinal systolic velocities during DOB stress by DTI is useful for the precise assessment of myocardial viability.
I investigated the relationship between the percentage of body fat, Body Mass Index (BMI) and total plasma cholesterol and blood pressure. The percentage of body fat was measured by the bioelectrical impedance method. The subjects investigated were 2,955 men aged from 23 to 59 years, who were working in a company making machinery. They were divided into four groups as follows. The normal group were within the normal BMI range (< 24) and body fat percentage range (< 20%). The seemingly obese group were over the normal BMI (> or = 24) and normal percentage of body fat range. The occult obesity group were within the normal BMI range and over the normal percentage of body fat range (> or = 20%). The obese group were over the BMI and percentage of body fat range. In each group, those who had high total plasma cholesterol and blood pressure were counted. The number of those who had high total plasma cholesterol was significantly larger in the obese group than in the seemingly obese group and the normal group, and larger in the occult obesity group than in the seemingly obese group and normal group and larger in the seemingly obese group than in the normal group. The number of those who had high systolic blood pressure was significantly larger in the obese group than in the occult obesity group, the seemingly obese group and the normal group, larger in the occult obesity group than in the normal group and larger in the seemingly obese group than in the normal group. The number of those who had high diastolic blood pressure was significantly larger in the obese group than in the occult obesity group, and the seemingly obese group and the normal group, larger in the occult obesity group than in the normal group, and larger in the seemingly obese group than in the normal group. These results suggest that measurement of percent body fat is useful in preventing adult diseases in employees with a high percentage of body fat, but who show no sign of abnormality in medical examinations, and those who are considered to be obese according to their BMI or percentage of body fat have a high risk of adult diseases.
In the home care for terminal stage cancer patients, the quality of life of patients has been regarded as more important than the QOL of their family. Now, however, we think the QOL of the family of the patients is as important as that of the patients themselves. We investigated the opinion of the families and nurses by questionnaire in the HPN care for terminal stage cancer patients and compared them. The family answered positively about HPN, but they had a negative opinion in that they do not want to undergo HPN because they felt a heavy burden and responsibility in caring for patients, and they do not want to cause these feelings in others in their family. The nurses also answered positively about HPN, and they answered that they want to undergo HPN if they have terminal stage cancer. These results suggest that the family feels a greater burden and responsibility in caring for patients at home than the medical staff realize. The medical staff should support the family as well as terminal stage cancer patients and should not force our own opinions as medical staff.
The role of families who care for home parenteral nutrition (HPN) patients is extremely important. They face many problems not only in caring for patients but also in their own lifestyle. We investigated by questionnaire the changes in the family of terminal stage cancer patients receiving HPN. Replies submitted to the questionnaire were obtained from 20 out of 32 families who underwent HPN in the Osaka Prefectural General Hospital. Ten out of 20 people answered that they changed their lifestyle during HPN. The changes were decreased opportunity to communicate with other people and decreased time for to spend on a hobby or other activity. The care of the HPN patients affects the wife, daughter-in-law and children more than the husband of the patient, because the former have to manage housekeeping as well as patient care. This result suggests that the quality of life of the family of terminal stage cancer patients at home with HPN declined because they had to change their own lifestyle in order to spare time to care for the patients.
The circulating levels of soluble Fas ligand was increased in patients with advanced congestive heart failure. This study also indicates that the failing heart may contribute to the increased concentration of soluble Fas ligand in patients with congestive heart failure.
In pig-to-human discordant xenotransplantation, human complement is a major barrier against long survival of xenografts. Human complement regulatory proteins expressed on xenografts have been adapted as safeguards against host-induced hyperacute rejection of xenografts. For successful xenotransplantation, there have been many attempts to generate molecules with potent human complement regulatory activity but without activities related to harmful functions such as infection, immunosuppression and signal transduction devastating cellular homeostasis. Here, we summarize the strategy by which molecules for xenotransplantation should be designed and propose a GPI-anchored form of monomeric human C4bp as a candidate for efficient protection of swine xenografts from human complement attack.
In most ectotherms, environmental temperature has differential effects on growth and differentiation. For example, amphibian size at maturity decreases with increasing temperature. To address how radiant heat in the form of far-infrared radiation (FIR) may affect development of the aquatic ectotherm Xenopus laevis, we continuously irradiated swimming larvae as they developed into young adults. Here we report evidence that FIR promotes growth of these organisms in an aqueous environment.
In this paper, we evaluated experimentally the feasibility of transferring a pedicled venous flap with perivenous areolar tissue into an ectopic site and investigated the role of each vein, the perivenous areolar tissue and nerve in the viability of pedicled venous flaps. Three groups of flaps were created using a rabbit-ear model: Group 1 (n = 11), containing perivenous areolar tissue and a draining vein; Group 2 (n = 10), perivenous areolar tissue, a draining vein and nerve; Group 3 (n = 10), only perivenous areolar tissue. Macroscopic, angiographic and histological assessments were performed 14 days after transfer. The total survival areas including superficial necrosis of Groups 1, 2 and 3 were 52.7%, 82.5% and 0%, respectively. There were significant differences in mean survival area and mean total survival area including superficial necrosis between Group 1 and Group 2 (P < 0.05). In contrast, all flaps in Group 3 became necrotic. These data suggest that a preserved vein is the necessary condition, and additional arterial flow through the preserved nerve and a small vascular network within the areolar tissue may play an important role in flap survival.
Numerous studies of grafted skin suggest that full-thickness skin grafts are nourished by exudate from the recipient bed called a serum imbibition. However, whether serum imbibition by itself is sufficient for nourishment of skin grafts has not been shown definitely and directly. To clarify the role of serum imbibition, we performed a comparative study between 20 skin grafts and 20 musculocutaneous flaps. The nourishment of the cell in the skin graft is by serum imbibition. That in musculocutaneous flaps is mainly derived from blood supply. We evaluated the nourishment by means of the unique characteristics of the cell cycle. Once cells are put into a synthetic phase, they cannot reverse or stop the progress of the cell cycle. To take advantage of this characteristic of the cell cycle, prewounding methods (40 flaps were lifted once and put back to the original sites prior to the evaluation) were intended for the cells in pre-elevated skin to turn into a proliferating phase. Cells were examined by antibody against proliferating cell nuclear antigen immunohistologically, to determine whether they had turned into the proliferating phase or not. After 3 days, all flaps were reelevated; half (20 flaps) had their muscle layer and the neurovascular bundle removed to make a full-thickness skin graft. The rest (20 flaps) were only lifted. They were sutured back to the original sites. Ten skin grafts and musculocutaneous flaps each were harvested at 3 hours (1st day) and at 11 days (11th day) after the second operation. Bromodeoxyuridine, which is a thymidine analog and is taken into the cells in the synthetic phase, was introduced intraperitoneally 2 hours before the harvest. All flaps and grafts were evaluated histologically and immunohistologically. Proliferating cell nuclear antigen analysis showed that the prewounding method induced the cells of skin grafts and musculocutaneous flaps to proliferate before the implantation. Regarding the bromodeoxyuridine uptake, no significant differences could be seen between skin grafts and musculocutaneous flaps irrespective of their different nourishment. No structural changes, such as degenerative or necrotic, could be seen at the hair follicle and other glands even at the 11th day. Almost all of the layers of skin grafts survived as long as they were checked by light microscopy (hematoxylin and eosin stain). No differences could be seen between musculocutaneous flaps and skin grafts or between the 1st and 11th days in this study. We concluded that serum imbibition is sufficient for nourishment of skin grafts, just as blood supply is sufficient for nourishment of musculocutaneous flaps.
PROBLEM: We evaluated the participation of the lymphocyte subpopulations in the endometrium and peripheral blood on in vitro fertilization and embryo transfer (IVF-ET) outcomes. METHOD OF STUDY: Peripheral blood samples were analyzed for the expression of CD3, CD4, CD8, CD16, and CD56, using a FACScan, and for natural killer (NK) cell cytotoxicity, using a 51Cr assay. Endometrial samples obtained at a previous phase of the IVF cycle were analyzed for the expression of CD16 and CD56, using a FACScan. RESULTS: The percentages of CD56+ cells and CD16+CD56+ cells in the peripheral blood on the day of ET were significantly higher in the failed group than in the implanted group. In the endometrial tissue, the increase of the percentage of CD16+CD56dim cells and the decrease of the percentage of CD16-CD56bright cells in the aborted group were significant when compared with the those of the delivered group. CONCLUSIONS: The increase of cytotoxic NK cells in the peripheral blood and the endometrium may affect the therapeutic results of IVF-ET. It was suggested that modifications of NK cytotoxicity or of NK subpopulations might contribute to the improvements of IVF outcomes.
Human membrane cofactor protein (MCP, CD46) is a regulator of complement activation and also serves as a receptor for measles virus (MV). We recently isolated an MCP homolog from B95a, an Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line, which is 76% identical to human-MCP. B95a-MCP acts as an MV receptor for CAM, a vaccine strain of MV, but not for Nagahata, wild-type MV strain. The four residues in human-MCP (Asp27, Lys29, Arg69, and Asp70) are reportedly MV binding sites, and these are changed in B95a-MCP (Glu27, Asp29, Pro69, and Asn70). In the present study, we constructed B95a-MCP mutants by replacing the four residues with those in human-MCP, and tested whether the Chinese hamster ovary (CHO) transfectants expressing B95a-MCP mutants become susceptible to the Nagahata strain. The CHO transfectants expressing B95a-MCP mutants formed syncytium with the CAM strain but not with the Nagahata strain. The binding of the hemagglutinin (H) of MV with B95a-MCP mutants was observed with the CAM strain but not with the Nagahata strain. These results suggest that the failure of B95a-MCP as the MV receptor for the Nagahata strain is not due simply to the natural mutations at these four residues. The critical residues for MV binding in an MCP molecule seem to differ depending upon the structure of the MV H protein.