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Biomedical subjects

T Sugihara

Publications and source records attributed to T Sugihara.

At least 145 records · Page 8Linked to original sources

Antithrombotic effect of recombinant human soluble thrombomodulin on endotoxin-induced disseminated intravascular coagulation in rats.

Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which neutralizes thrombin procoagulant activity and accelerates the thrombin-catalyzed activation of protein C. We expressed recombinant human soluble TM (rhs-TM) in Chinese hamster ovary cells and compared the effects of rhs-TM and heparin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a continuous intravenous infusion of endotoxin for four hours. rhs-TM or heparin was infused simultaneously with endotoxin. Treatment with rhs-TM significantly reversed the endotoxin-induced changes in significantly reversed the endotoxin-induced changes in following parameters: platelet count, fibrinogen level and fibrinogen and fibrin degradation products. Furthermore, glomerular fibrin deposits elevated by endotoxin treatment were reduced by the rhs-TM administration. Heparin showed the similar effects to rhs-TM. Activated partial thromboplastin time (APTT) in rats receiving rhs-TM were slightly longer than APTT in endotoxin-treated rats, but rats receiving heparin had much more prolonged APTT. From these results, we concluded that rhs-TM may be useful for the clinical treatment of DIC while having only minor adverse effects on APTT.

Animals↗

Abdominoplasty in paraplegic patients.

Obese paraplegics can suffer discomfort when they lie in a prone position and site in wheelchairs. Two paraplegic cases who underwent abdominoplasty to eliminate such complaints are presented, with satisfactory results.

Abdominal Muscles↗

Midface advancement by gradual distraction.

Midface osteotomy was performed on 5 young adult sheep aged 10-12 months. In 4 animals midface advancement by gradual distraction was performed using an external device; one animal served as a control. The midface was advanced by 2 mm per day for 21 days. The amount of advancement was 36 mm in the nasofrontal area and 43 mm on the lateral aspect of the maxilla. After the period of active distraction the midface was maintained with external fixation for an additional 6 weeks to allow for ossification. Radiographs were obtained immediately postoperatively, after 21 days of distraction, and at the end of the 6 week fixation period. New bone formation in the distracted area was obvious radiographically, clinically and histologically. In conclusion, midface advancement by osteotomy and gradual distraction is possible in the sheep model and may offer controlled correction of deformity, obviating the need for the bone grafting.

Animals↗

Diphenylamine: an unusual antioxidant.

Diphenylamine (DPA) has been utilized as an antioxidant in studies of lipid peroxidation. Using peroxidizing red blood cell (RBC) membranes, we find that DPA actually promotes lipid hydroperoxide (LOOH) formation and oxygen consumption while markedly inhibiting generation of thiobarbituric acid reactive substances (TBARS). As a consequence, DPA increases the prelytic RBC K leak that results from peroxidative stress and potentiates a known nonprelytic but LOOH-dependent K leak pathway in RBC. In contrast, DPA abolishes formation of cyclooxygenase-dependent conversion products of arachidonate. DPA is almost as efficient as BHT in inhibiting peroxyl radical mediated destruction of phycoerythrin fluorescence. Study of DPA analogues shows that the antioxidant effect of DPA lies in its secondary amine function. Presumably, this results in intermediate formation of a nitrogen-based radical so that redox cycling of this aromatic amine stimulates further peroxidation. This dramatically illustrates the hazard of relying solely on TBARS measurements for assessment of peroxidation.

Antioxidants↗

Role of bone graft in reconstruction of skull base defect: is a bone graft necessary.

Ten patients underwent reconstruction of skull base defects between 1989 and 1992. In this series, the maximum size of the skull base defect was 6 x 5 cm. Three patients underwent bone grafts to reinforce the skull base. The postoperative course of seven patients without bone grafts was uneventful. There was no cerebrospinal fluid leakage, meningitis, extradural abscess, on brain herniation. On the other hand, two of the three patients with bone grafts developed extradural abseesses requiring the bone grafts to be removed. Although the number of patients in this series is not large, this study demonstrates that the use of bone grafts in reconstruction of skull base detects could be one of the factors in increasing the chances of infectious complications. We think that a bone graft is not necessary to reconstruct moderate-sized skull base defects.

Journal Article↗

Superiority of the fasciocutaneous flap in reconstruction of sacral pressure sores.

The gluteal maximus muscle has been used in the treatment of sacral pressure sores since the 1970s. However, it is noted that the muscle portion of the transferred flap shows highly atrophic degeneration and the muscle itself is not suitable tissue for covering the pressure-bearing area. We have managed various fasciocutaneous flaps as the first choice for reconstruction of sacral pressure sores and obtained good results. The fasciocutaneous flap has an anatomical structure that resists physical stimulation or external pressure and an abundant blood supply via its fascial plexus. In addition, if we use a gluteal maximus myocutaneous flap at first, some fasciocutaneous flaps are compromised because of the design and blood supply. We suggest that the fasciocutaneous flap has the first priority and is superior to the gluteal maximus myocutaneous and muscle flaps in reconstruction of sacral pressure sores.

Adult↗

Double cross lip flaps for reconstruction of the lower lip.

Squamous cell carcinoma of the lower lip is a common tumor. Of the many methods available for reconstructing lower lip defects after radical excision, we found double cross lip flaps from each lateral side of the upper lip philtrum rotated into the defect of the lower lip to be an effective method, not only functionally but also cosmetically. The main reason why satisfactory results were obtained by this procedure is that the anatomical structure (skin-orbicularis oris muscle-mucosa, vermilion) of the upper lip is very similar to that of the lower lip. Our experience is with double cross lip operations in the management of lower lip cancers are described.

Adult↗

Pharmacokinetics of meropenem in experimentally burned rats.

The pharmacokinetics of meropenem were investigated to examine its penetration into the skin of third degree burned rats. The rats were divided into two groups. One group acted as the control, and the other group had third degree burns induced by immersing their backs into 80 degrees C water for 20 seconds. The rats in each group were given 20 mg/kg of body weight of meropenem intravenously by one bolus injection seven days after burn inducement or depilation. In the non-burned control group, the maximum concentrations of meropenem in the serum and skin of 6.03 micrograms/ml and 0.12 microgram/g were respectively obtained 15 minutes after the injection and decreased very rapidly thereafter. In the burned rats, the maximum concentrations of meropenem in the serum, skin (eschar), and exudate fluid of 7.07 micrograms/ml, 1.44 micrograms/g and 5.99 micrograms/ml were respectively obtained 15 minutes after the injection and decreased very slowly. The penetration of meropenem into the burned skin was higher than that into the normal skin. These results suggest that meropenem is a very useful antibiotic in the treatment of burn infection.

Animals↗

Primary correction of the unilateral cleft lip nose.

The details of surgical techniques for primary correction of the unilateral cleft lip nose and their results for 45 cases are reported. The technique employed an infracartilaginous incision on the affected side, thus allowing direct suturing of the alar cartilage onto the lateral cartilage. For the post-operative evaluation, the nasal form in both frontal and bottom views was scored for five items. In overall evaluation, the grades of "Good," "Fair," and "Poor" were derived from the total scores of five items. In the postoperative results (range of follow-up: 24 months to 84 months), 24 cases were rated "Good" (53.3%), 13 cases "Fair" (28.9%), and 8 cases "Poor" (17.8%). Thirty cases appear not to need secondary correction (66.6%). The technique is useful because the alar cartilages and lateral cartilages can be accurately sutured, and relatively stable results can be obtained.

Cleft Lip↗

Silent mixed ganglioneuroma/pheochromocytoma which produces a vasoactive intestinal polypeptide.

An unusual pheochromocytoma was incidentally discovered in a 48-year-old woman. The patient had a 3-year history of myasthenia gravis. At the time of examination in our hospital, the right adrenal tumor was incidentally discovered by ultrasonography of the abdomen. She had no history of headache, perspiration, palpitation or hypertension. Although blood catecholamine levels were within the normal limits, urinary secretion of catecholamine was elevated. Histologically, the tumor was diagnosed to be mixed ganglioneuroma/pheochromocytoma and histochemically confirmed to produce vasoactive intestinal polypeptide. Such a tumor is quite rare.

Adrenal Gland Neoplasms↗

[Analysis of chronic graft-versus-host disease in patients after bone marrow transplantation from HLA-identical siblings].

The incidence of chronic GVHD, involved organs, and outcome were evaluated in 59 patients aged 15 years or more who survived for 2 months or more after HLA-matched bone marrow transplantation. The incidence of chronic GVHD was 65.3%. The incidence was not correlated with the age at the time of transplantation, underlying disease, or the method to prevent GVHD (group treated with MTX alone and CSP-treated group). Concerning the degree of organ involvement, the CSP-treated group more frequently showed slight involvement and, especially a significantly lower incidence of dryness of the eyeballs. According to organs, the oral cavity was most frequently involved (87%), followed in order by the liver (74%), skin (52%), and the eyes (30%). The oral cavity alone was involved in 6 patients, and the outcome was generally good. The outcome of multi-organ involvement of chronic GVHD was poor, and the major causes of death were interstitial pneumonia and sepsis. Even of patients who did not develop chronic GVHD, 25% showed dryness of the eyeballs and oral cavity. Biopsy and careful observation of the clinical course are needed for diagnosing GVHD.

Adolescent↗

[Treatment of aplastic anemia with antithymocyte globulin, Lymphoser Berna].

Twenty-four patients with aplastic anemia (19 severe: 5 moderate) were treated with combined immunosuppression consisting of antithymocyte globulin (ATG: Lymphoser Berna, Swiss Serum and Vaccine Institute Berne) and high-dose methylprednisolone. Danazol or meptiostane was administered concurrently for at least 3 months. Three batches of ATG were used, two were not absorbed with thrombocytes and one was absorbed with thrombocytes for the prevention of thrombocytopenia. Nine of 20 evaluable patient (45%) had sustained improvement in hematopoiesis within 3 months of treatment. Nine of 14 patients (64%) showed a response to ATG without thrombocyte absorption, on the other hand, none of 6 patients responded to ATG with thrombocyte absorption. By life table analysis, the 3 year probability of survival was 81 +/- 27% after the combined immunosuppressive therapy. These results indicated that ATG therapy was very effective in Japanese patients with aplastic anemia.

Adolescent↗

Laserflowgraphy: a new visual blood flow meter utilizing a dynamic laser speckle effect.

We developed a visual laser blood flow meter that is capable of providing two-dimensional color graphic representations of blood flow distribution for a given area by utilizing a dynamic laser speckle effect. The device is called the laserflowgraph. The principle and configuration of this flowmeter, comparison with the 133Xe clearance method, difference from thermography, and clinical uses of this flowmeter in flap monitoring are presented. Flow level of the laserflowgraph was significantly correlated with blood flow rate determined by 133Xe clearance in observations on the forearms of normal volunteers. The laserflowgraph reflected blood flow through the region between the skin surface and the deeper region of the papillary layer of the dermis. The laserflowgraph is a highly useful, practical, and reliable tool for assessing cutaneous blood flow and is expected to be applicable to various clinical fields.

Adult↗

Prefabricated flaps using tissue expanders: an experimental study in rats.

The aim of this study was to determine if muscle vascularized pedicle flaps (MVP flaps) elevated in expanded tissue on the rat would survive to the same or greater area than flaps elevated in nonexpanded tissue. The animals were divided into three groups: group I (n = 10), with a tissue expander; group II (n = 10), with a tissue expander but not expanded; and group III (n = 10), with a thin silicone sheet (Biobrane). The mean surviving area of group I (96.6 +/- 3.6 percent) was statistically higher than that of group II (73.2 +/- 24.7 percent) (p < 0.05) and group III (59.5 +/- 25.1 percent) (p < 0.005). These experiments demonstrate that there is a larger area of flap survival in expanded muscle vascularized pedicle flaps than that found in nonexpanded flaps in rats. The mechanism of increased vascularity associated with tissue expansion is still unclear, but microangiography of flaps showed increased vascularity of the pedicle itself, especially in group I.

Angiography↗

Thrombospondin mediates adherence of CD36+ sickle reticulocytes to endothelial cells.

Initiation of vasocclusion in sickle disease pathophysiology may involve abnormal red blood cell (RBC) adhesivity to endothelium, a phenomenon influenced by both RBC and plasma factors. Using human umbilical vein endothelial cells and a gravity sedimentation adherence assay, we have examined thrombospondin (TSP) as a plasma factor in this adhesive event. The already-abnormal adherence of sickle RBCs in buffer/albumin is significantly augmented (P < .001) by the addition of TSP, with half-maximal effect at about 0.3 microgram/mL. This effect is abolished by antibodies to either TSP or glycoprotein (GP) IV (CD36), as well as peptides RGDS and CSVTCG. The even greater adherence (P < .005) of sickle RBCs in autologous platelet-rich plasma (without added TSP) is dramatically inhibited by alpha CD36 antibodies (OKM5 and alpha GPIV) and significantly diminished by alpha TSP, by peptides RGDS and CSVTCG, and by two antibodies to the vitronectin receptor (7E3 and LM609). Studies of density-separated subpopulations and of RBC adhesion to immobilized proteins, as well as analysis of sickle RBCs using fluorescence-activated cell sorting and single cell microfluorometry, show that TSP responsiveness is a feature of the immature sickle "stress" reticulocytes, which carry CD36 (and not GPIIbIIIa-like receptors) as the TSP-receptive moiety. The endothelial cell's participation in this phenomenon appears to be more complex, and the data are consistent with the notion that it involves TSP interaction with other plasma proteins and/or multiple receptor structures. Other potential adhesogenic proteins (plasma von Willebrand factor, vitronectin, fibrinogen, and fibronectin) neither exhibited an affinity for reticulocytes nor supported increased sickle RBC adherence when added to buffer/albumin in these assay systems. In aggregate, our results indicate that TSP may be the major promoter of RBC adhesivity in plasma, and they suggest that therapeutic benefit might derive from interference with sickle reticulocyte CD36, as achieved by antibodies and CSVTCG in these studies.

Anemia, Sickle Cell↗

Exaggerated cation leak from oxygenated sickle red blood cells during deformation: evidence for a unique leak pathway.

An abnormal susceptibility of the sickle red blood cell (RBC) membrane to deformation could compromise its permeability barrier function and contribute to the exuberant cation leakiness occurring during the sickling phenomenon. We examined this hypothesis by subjecting RBCs at ambient oxygen tension to elliptical deformation, applying shear stress in a viscous medium under physiologic conditions. Compared with normal and high-reticulocyte control RBCs, sickle RBCs manifest an exaggerated K leak response to deformation. This leak is fully reversible, is both Cl and Ca independent, and at pHe 7.4 is fully balanced so that Kefflux equals Nainflux. This abnormal susceptibility is also evident in that the K leak in response to deformation occurs at an applied shear stress of only 141 dyne/cm2 for sickle RBCs, as compared to 204 dyne/cm2 for normal RBCs. Fresh sickle RBC membranes contain elevated amounts of lipid hydroperoxide, the presence of which is believed to provide the biochemical basis for enhanced deformation susceptibility. When examined at pHe 6.8, oxygenated sickle RBCs acquire an additional, unbalanced (Kefflux > Nainflux) component to the K leak increment specifically ascribable to deformation. Studies with inhibitors suggest that this additional component is not caused by a known leak pathway (eg, either K:Cl cotransport or the Gardos channel). This abnormal susceptibility of the sickle membrane to development of cation leakiness during deformation probably contributes to the exuberant cation leak taking place during RBC sickling.

Anemia, Sickle Cell↗

Periodicity of episode occurrences in rapid cycling affective disorders.

We analyzed the medical records of nine patients with severe rapid cycling affective disorders (RCAD), and determined the cycle of mania occurrences by calculating the period between two successive onsets of mania for each patient. Using the cycle as the index we devised a cycle-oriented diagram by dividing the observation period by the index cycle, and visually studied the mode of episode occurrences. In seven patients, the onset of mania generally followed the index cycle, but sometimes shifted from the day estimated by the index cycle. The shift seemed to be caused by a cycle other than the index cycle, which appeared temporarily in the course. The period between two successive onsets of mania was often several times longer than the index cycle length. In patients with RCAD, some sort of periodic rhythms may possibly control the course of episode occurrences on a continuing basis.

Adult↗

Phospholipid asymmetry during erythrocyte deformation: maintenance of the unit membrane.

To assess the red blood cell (RBC) membrane's ability to maintain normal phospholipid orientation in the face of deforming stress, we examined RBC subjected to elliptical, tank-treading deformation. As determined by accessibility to phospholipase digestion and by labelling with fluorescamine, normal RBC are able to fully preserve their phospholipid asymmetry despite attaining over 96% of their maximal possible deformation. Phospholipid orientation is unchanged during deformation even for RBC that are ATP-depleted or vanadate-treated and for RBC that already have destabilized phospholipids due to treatment with t-butyl hydroperoxide. These data indicate that maintenance of phospholipid organization during marked deforming stress and tank-treading motion of the membrane is ascribable predominantly to the passive stabilizing effect of membrane proteins. This provides additional evidence for the concept of a unit membrane characterized by intimate associations between lipid and protein.

Cations↗