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Biomedical subjects

S Mizumoto

Publications and source records attributed to S Mizumoto.

At least 19 recordsLinked to original sources

Production of lipopeptide antibiotic iturin A using soybean curd residue cultivated with Bacillus subtilis in solid-state fermentation.

Bacillus subtilis RB14-CS, which suppresses the growth of various plant pathogens in vitro by producing the lipopeptide antibiotic iturin A, was cultured using soybean curd residue, okara, a by-product of tofu manufacture in solid-state fermentation. After 4 days incubation, iturin A production reached 3,300 mg/kg wet solid material (14 g/kg dry solid material), which is approximately tenfold higher than that in submerged fermentation. When the okara product cultured with RB14-CS was introduced into soil infested with Rhizoctonia solani, which is a causal agent of damping-off of tomato, the disease occurrence was significantly suppressed. After 14 days, the number of RB14-CS cells remained in soil at the initial level, whereas almost no iturin A was detected in soil. As the okara cultured with RB14-CS exhibited functions of both plant disease suppression and nutritional effect on tomato seedlings, this product is expected to contribute to the recycling of the soybean curd residue.

Bacillus subtilis↗

Innervated radial thenar flap combined with radial forearm flap transfer for thumb reconstruction.

A radial thenar flap combined with radial forearm flap was used for the reconstruction of the ipsilateral thumb in four patients. Vascular supply of the combined flap was based on the radial artery and extending the vascular pedicle to the superficial palmar branch of the radial artery. The flap was sensated by the palmar branch of the superficial radial nerve. The size of the flap averaged 15 x 5 cm and the innervated region of the thenar eminence was an area approximately 5 x 3 cm located over the proximal parts of the abductor pollicis brevis and opponens pollicis muscles. The flap was transferred as a free flap in three patients and as an advancement flap in one patient. The flaps survived completely without complications. Satisfactory restoration of sensation was achieved in the flap area, as shown by 6 mm of average moving two-point discrimination. This combined flap may be a feasible reconstructive option for large palmar defects of the fingers such as degloving injuries.

Adult↗

P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus.

The incidence of adenocarcinomas in Barrett's esophagus has been rising in the last two decades in the United States and Western Europe for yet unknown reasons. We reported previously a large multi-institutional trial implicating p53 mutations as being involved in the pathogenesis of Barrett's cancer and representing an early marker for the malignant potential of Barrett's epithelium. A prospective study was performed to evaluate the prognostic impact of p53 mutations on survival in 59 patients with Barrett's cancer. Tissue for DNA analysis was obtained by endoscopic biopsy or immediately after surgical resections from the tumor, Barrett's epithelium, and normal stomach and esophagus. p53 mutation analysis was performed by PCR-single strand conformational polymorphism screening of exons 5-9 and DNA sequencing to unequivocally prove the presence of a mutation. p53 mutations were identified in 30 of 59 (50.8%) patients. The presence of a p53 mutation in the tumor had a significant impact on survival after curative resections (RO-resections) with cumulative 5-year survival probabilities of 68.8+/-9.7% for mutation-negative tumors and 24.3+/-9.9% for mutation-positive tumors (log rank: P < 0.001). By Cox proportional hazard analysis, including the parameters of gender, age, Union International Contre Cancer tumor stage, grading, and p53 mutation status, only Union International Contre Cancer tumor stage (P < 0.0001) and p53 mutation status (P < 0.02) were of significant independent prognostic importance. p53 mutation analysis by DNA sequencing is of significant independent prognostic importance next to histopathological tumor stage in patients with curatively resected (RO-resection) Barrett's cancer. It appears that p53 mutational status is a valuable parameter to define low-risk (p53 mutation-negative) and high-risk (p53 mutation-positive) groups for treatment failure after curative resections.

Adenocarcinoma↗

Small dipeptide-based HIV protease inhibitors containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic.

The human immunodeficiency virus (HIV) codes for an aspartic protease known to be essential for retroviral maturation and replication. HIV protease is formed from two identical 99 amino acid peptides. We synthesized [(NHCH2CH2-S-CH2CO)51-52, Ala67,95]HIV-1 protease using the thioether chemical ligation method, and then prepared the [(NHCH2CH2-S-CH2CO)51-52, Ala67,95, Cys98]HIV-1 protease dimer analogue covalently linked by a disulfide bridge. These HIV-1 protease analogues effectively cleaved the Tyr-Phe-type substrate, but had weak affinity to the Tyr-Pro-type substrate. Consequently, the molecular recognition of the protease analogues differs from that of the wild-type enzyme. Based on the substrate transition state, we designed and synthesized a novel class of HIV protease inhibitors containing an unnatural amino acid, (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid, named allophenylnorstatine, with a hydroxymethylcarbonyl (HMC) isostere. The stereochemistry of the hydroxyl group was significant for the enzyme inhibition and the HMC group interacted excellently with the aspartic acid carboxyl groups of HIV protease active site in the essentially same hydrogen-bonding mode as the transition state. Small dipeptide-based HIV protease inhibitors containing the HMC isostere were studied as advantageous compounds. Among them, a dipeptide-based HIV protease inhibitor, KNI-577, exhibited potent antiviral activities, low cytotoxicity, and good pharmacokinetic properties.

Amino Acid Sequence↗

Osteocutaneous radial forearm flap for hand reconstruction.

We treated 5 patients (4 men and 1 woman) with bone and soft tissue defects or total thumb loss using an osteocutaneous radial forearm flap. Their ages at the time of surgery ranged from 27 to 65 years (mean, 53 years). Preoperative conditions were traumatic loss of the thumb in 3 cases and severe injuries with soft tissue and bone defects in 2. The length of the donated radius ranged from 2 to 7 cm (mean, 4.7 cm). In 4 patients the radial forearm flap was transposed, including the lateral antebrachial cutaneous nerve as a sensory flap. Simultaneous iliac bone grafting to the donor site was also performed in 4 of the cases. The follow-up period ranged from 44 to 87 months (mean, 64 months). All flaps survived over their full extent. Radiographic bone union was attained after 2 to 3 months (mean, 2.5 months). Two-point discrimination over the 4 sensory flaps ranged from 8 to 15 mm (mean, 10.8 mm). No radius fractures occurred. No patients showed signs of vascular insufficiency from sacrifice of the radial artery. The radial forearm flap provides thin skin of good texture together with bone for a 1-stage reconstruction. For patients with skin and bone defects of the hand, a radial forearm osteocutaneous flap is recommended. This flap is also recommended for patients with traumatic thumb loss, if the dorsalis pedis artery is absent, or if the patient declines using tissue from the foot.

Adult↗

Subzero nonfreezing preservation in a murine limb replantation model.

This study was designed to examine the most effective temperature for hypothermic storage, without freezing, to prolong ischemic tolerance in an amputated murine hindlimb model. We measured freezing points in the calf muscle and the subcutaneous tissue of the foot in the amputated limbs of Fisher 344 strain male inbred rats. The highest freezing point was -1.5 degrees C, which was recorded in the calf muscle. To prevent freezing in any of the tissues in the amputated limb, the temperature for the lowest nonfreezing preservation was defined as -1 degrees C. The amputated limbs were preserved at subzero nonfreezing temperature (-1 degrees C) and at 4 degrees C for 4, 8, 12, 24, 48, and 72 h, and were then transplanted to other inbred rats by microsurgical techniques. We evaluated the vascular patency of the anastomoses by direct observation and performed histological examinations on the seventh day after replantation. Subzero nonfreezing preservation of a limb at -1 degrees C for 72 h was significantly superior to hypothermic preservation at 4 degrees C for 72 h in terms of anastomotic patency rates (P < 0.05). The histology of skeletal muscles preserved at -1 degrees C for 8 h showed greater similarity to the normal situation than the histology of those preserved at 4 degrees C for 8 h. Bone viability with osteoblastic activity was maintained in grafted limbs preserved at -1 degrees C for 72 h, but in the limbs preserved at 4 degrees C for 72 h the bone was not viable, showing no osteoblastic activity. Clinically, the period of ischemia in major limb replantation at normal ambient temperatures is limited to about 6 h. In this study, the maximum ischemia time for replantation of a limb containing muscle tissue was prolong to 8 h at -1 degrees C, but the maximum ischemia time at 4 degrees C could not be prolonged to 8 h. Our results suggest that, in the major replantation of a limb containing muscular tissue, hypothermic preservation at -1 degrees C would be more useful than preservation at 4 degrees C.

Animals↗

Mechanisms producing color change in flat early gastric cancers.

BACKGROUND AND STUDY AIMS: Although highly refined endoscopes have made it possible to detect not only early gastric cancers with morphological changes, but also flat-type tumors (type IIb) on the basis of the color changes observed in them, the factors responsible for color changes in type IIb carcinomas have not been fully elucidated. The aim of this study was to analyze the potential mechanisms underlying these color changes. PATIENTS AND METHODS: Thirteen type IIb cancers were selected from a total of 589 resected gastric cancers detected preoperatively using endoscopic examination. All of the tumors showed color changes alone, without surface changes, and the color changes included redness, discoloration, and spotty bleeding. Detailed histological examination of the resected stomachs revealed twelve more II b lesions that had not been identified at endoscopy. The endoscopic appearance of the IIb cancers were correlated with the degree of tumor differentiation, the extent of wall infiltration, and the number of capillaries. RESULTS: In cases that were detectable by endoscopy, the endoscopic color appearance correlated significantly with both tumor size (P < 0.02) and with the extent of mucosal cancer infiltration (P < 0.02). Histological examination of the IIb lesions revealed that redness and discoloration were significantly more frequent in the differentiated and undifferentiated cancer types, respectively (P < 0.01). There was a significant difference in the number of capillaries between type IIb carcinoma and the adjacent normal mucosa, but not between cancers. The numbers for differences in redness and discoloration were 7.0 +/- 5.6 and -14.0 +/- 8.8, respectively. CONCLUSIONS: These results suggest that the main factor underlying color change in type IIb early gastric cancers may be the number of capillaries in the lesions, in comparison with the adjacent mucosa. Whether the lesion is visible on endoscopy, however, depends more on its size than on the number of capillaries.

Adult↗

Vascular compliance and vasoconstrictive reactions in rat hindlimbs: comparison between storage temperatures of -1 degree C and 4 degrees C.

The vascular compliance and contractility of vascular smooth muscle of rat freshly amputated hindlimbs and hindlimbs preserved at -1 degree C for 12, 24, 48, and 72 hr were evaluated using a fresh blood extracorporeal circulatory system. Vascular compliance was measured under physiologic circulatory conditions (blood pressure of the amputated limb was maintained at 80 to 150 mmHg). Vascular compliance after storage at -1 degree C for 12 hr or longer decreased significantly from that of freshly amputated limbs (p < 0.01). To evaluate the contractility of vascular smooth muscle, the arterial blood pressure in the amputated limbs was transiently increased with injections of norepinephrine. The contractility after storage at -1 degree C for up to 24 hr was not different from that of freshly amputated limbs. However, it decreased significantly after 48 hr or longer. A comparison of these results with an earlier study that used identical methods to investigate limbs preserved at 4 degrees C suggested that storage at -1 degree C was inferior to that at 4 degrees C with respect to vascular compliance, but was superior to storage at 4 degrees C with respect to smooth muscle contractility.

Amputation, Surgical↗

Two-stage arterialized flow-through venous flap transfer for third-degree burn defects on the dorsum of the hand.

A modified, two-stage arteriovenous flow-through venous flap was designed to repair skin defects due to third-degree burns on the dorsum of the hand in four patients. Two weeks after plasty of an arteriovenous (A-V) shunt between the greater saphenous vein and dorsalis pedis artery, the arterialized flow-through venous flap was transferred using the greater saphenous vein as the pedicle. The size of the flaps utilized ranged from 7 x 13 cm to 9 x 13 cm. In three patients the entire flap survived without complication. In one patient whose flap had only one drainage vein, the flap survived with superficial necrosis of about 10 percent of the flap at the borders. During the 2 weeks after A-V shunt creation, the authors believe that microcirculation around the arterialized vein probably develops, contributing to better irrigation and thereby to flap survival. Using this two-stage procedure, it might be feasible to obtain larger grafts and to attain a higher flap survival rate.

Adult↗

Vascularized fibular graft for reconstruction of the wrist after excision of giant cell tumor.

Seven patients with a giant-cell tumor involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. Two patients with stage 2 disease of Enneking's surgical staging and grade 2 of Campanacci's radiographic grading system were reconstructed with an articular fibular head graft. Five patients with stage 3 and grade 3 disease underwent wrist arthrodesis using fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. No local recurrence was seen in any of the patients at the most recent follow-up examinations. There were six good and one excellent functional results. Wrist arthroplasty using a vascularized fibula head graft is the best procedure for a stage 2 or grade 2 giant-cell tumor of the distal end of the radius. In cases of stage 3 or grade 3 disease, wrist arthrodesis using a vascularized fibular shaft graft is indicated.

Adolescent↗

Innervated radial thenar flap for sensory reconstruction of fingers.

A radial thenar flap, which is supplied by the superficial palmar branch of the radial artery and innervated by the superficial branch of the radial nerve, was used in four patients for sensory reconstruction of the fingers. Two patients had degloving injuries of the hand and two had amputation injuries of the thumb. Three of the cases underwent free-flap transfers, and one case underwent a reverse-flow island flap. The size of these flaps was about 3 x 5 cm except in one case, where a 15 x 5 cm flap combined with a radial forearm flap was used. Sensory reinnervation was excellent and donor site morbidity was minimal in all four cases. An innervated radial thenar flap from the ipsilateral hand offers an alternative choice to reconstruct large palmar defects of the fingers.

Adolescent↗

Evaluation of vascular compliance and vasoconstrictive reactions in amputated hindlimbs of rats.

The vascular compliance and the contractility of vascular smooth muscle of preserved, amputated hindlimbs of rats were evaluated using a fresh blood extracorporeal circulatory system. Vascular compliance was measured under physiologic circulatory conditions (blood pressure of the amputated limb was maintained at 80-150 mm Hg [10-20 kPa]) and found not to differ significantly from that of freshly amputated limbs after storage at 4 degrees C for 12 hours. However, after more than 24 hours of storage at 4 degrees C, the vascular compliance decreased significantly (p < 0.01). To evaluate the contractility of vascular smooth muscle, the arterial blood pressure in the amputated limbs was transiently increased with injections of norepinephrine. The contractility could be preserved for at least 12 hours at 4 degrees C; however, it decreased markedly after more than 24 hours. The vascular compliance and vasoconstrictive reactions of the amputated limbs were maintained for at least 12 hours at 4 degrees C.

Amputation, Surgical↗

Venous flap--its classification and clinical applications.

We previously reported pedicled venous flap survival using the rat model, as well as venovenous, arteriovenous, and arterialized flow-through venous flap survival using the rabbit ear model. For this study, we utilized these flaps clinically. Five of seven pedicled venous flaps survived, displaying superficial necrosis. The others became partially necrotic; they were transferred after dissection of a long pedicle vein. Eight of nine venovenous flow-through venous flaps survived; six displayed superficial necrosis. The nonsurviving flap became completely necrotic, possibly because only one donor vein and one recipient vein were used. Six of 10 arteriovenous flow-through venous flaps survived. The remaining four became partially necrotic, possibly because only one vein was anastomosed for outflow. The arterialized flow-through venous flap survived. The pedicled venous and venovenous groups studied seem likely to survive despite superficial necrosis. However, the draining vein should not be dissected more than 5 cm, and many draining veins should be anastomosed with recipient vessels.

Adult↗

Preservation of the vasodilative effect of endothelium-derived relaxing factor in the hind limb of the rat.

Using an extracorporeal circulatory system of fresh blood, the vasodilative effect of endothelium-derived relaxing factor (EDRF) secreted from vascular endothelium, stimulated by acetylcholine (ACh), was evaluated. The bioassay cascade technique was applied to elucidate the release of EDRF. Elevated blood pressure of freshly amputated rat hind limbs, created by injection of norepinephrine (NE), decreased by 56% with ACh infusion, suggesting the existence of EDRF in the peripheral vascular system of rat hind limbs. The vasodilative effect of EDRF could be preserved for at least 6 hours when stored at room temperature. The effect of EDRF decreased markedly following storage for more than 9 hours at room temperature and storage for more than 3 hours at 4 degrees C.

Acetylcholine↗

[Hypervascular liver metastases of gastric cancer completely responding to transcatheter oily chemoembolization using epirubicin hydrochloride, mitomycin C and lipiodol].

A 68-year old woman underwent transarterial oily chemoembolization using Lipiodol with epirubicin hydrochloride and mitomycin C for treatment of multiple hypervascular hepatic metastases of gastric cancer. The tumors showed a good fixation of Lipiodol with a complete biologic response. The tumor has been well controlled for eight months by only one chemoembolization on follow-up study. Transcatheter oily chemoembolization may be an effective treatment not only for hepatocellular carcinoma, but also for hypervascular liver metastases from gastrointestinal malignancies.

Adenocarcinoma↗

Vascular complications of vascularized composite tissue transfer: outcome and salvage techniques.

Two hundred fifty-two vascularized composite tissue transfers were performed from 1985 to 1992 at Nara Medical University Hospital. Free tissue transfers were performed in 185 patients and island tissue transfers in 67 patients. Of these, 39 flaps were reexplored because of vascular complications. On initial reexploration, vascular obstruction was found at the site of anastomosis or in the main vascular pedicle in 36 patients and in the perforating vessels to the monitor flap in three patients. Arterial thrombus occurred in 11 patients, venous thrombosis in 12, and both in nine. Twenty-five reexplored flaps were salvaged. Initially, heparin was administered systemically when vascular compromise was suspected intraoperatively or postoperatively. Recently, we have used a "continuous local heparinization" technique to minimize blood loss. This method has been used in 12 patients who underwent reexploration and in nine patients in whom vascular compromise was suspected. Nineteen flaps survived completely, and two flaps failed.

Adolescent↗

The arterialised venous flap: experimental studies and a clinical case.

It is accepted that small arterialised venous flaps (AVF) can survive on a recipient bed with poor blood supply but survival of larger flaps is not always satisfactory. Possible reasons for this include the flap anatomy, particularly the pattern of the venous network, or factors at the recipient site. To investigate the possible factors in the flap design and the recipient site of an arterialised venous flap, we studied the relationship between (1) size of the artery used to arterialise the flap at the recipient site and the survival rate and (2) the number of draining veins and the survival rate, using rabbit ear skin flap models. Our results suggest that AVFs may become necrotic in the presence of a relative excess of arterial blood inflow, and that two exit veins are more effective than one. We also report a case where a 10 x 15 cm sized free AVF harvested from the lower extremity survived on the forearm.

Adult↗

Non-radioactive coloured microsphere measurement of regional tissue blood flow for axial pattern flaps in rabbits.

We administered non-radioactive coloured microspheres (NRACM) to measure the regional tissue blood flow (RTBF) of eight axial pattern flaps and four kidneys in four rabbits using four repeated injections into each animal. As a control, we used radioactive microspheres (RAM) for six kidneys in three rabbits. There were no significant differences for RTBF values between NRACM and RAM, between the numbers of microspheres used (2 x 10(6) and 4 x 10(6)), or between the number of injections. These results showed that NRACM is a useful and safe laboratory method.

Animals↗