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Biomedical subjects

S Sugimoto

Publications and source records attributed to S Sugimoto.

At least 37 records · Page 2Linked to original sources

Glucagon-like peptide isolated from the eel intestine: effects on atrial beating.

A new glucagon-like peptide was isolated from the intestine of the eel Anguilla japonica. The primary structure was determined by sequence analysis after cleavage with lysyl endopeptidase, quantitative amino acid analysis and fast atom bombardment mass spectrometry as HSQGTFTNDY(10)SKYLETRRAQ(20)DFVQWLMNSK(30)RSGGPT. Since its structure is similar to that of oxyntomodulins (OXMs) reported in various vertebrates, we named this peptide eel oxyntomodulin (eOXM). We found that eOXM enhanced the contractile force and the beating rate of the eel atrium in a dose-dependent manner. These effects of eOXM were not inhibited by betaxolol, a beta(1)-adrenoceptor antagonist, indicating that the actions of eOXM were independent of those of adrenaline. eOXM enhanced the intracellular Ca(2+) concentration of the myocardium. The contractility of the eel atrium was greatly reduced after omitting Ca(2+) from the bathing medium or after treatment with verapamil, a Ca(2+) channel blocker. After inhibiting Ca(2+) entry under these conditions, the inotropic effect of eOXM was markedly reduced, but the chronotropic effect was not altered significantly. These results indicate that the inotropic effect of eOXM is via a stimulation of Ca(2+) influx but that the chronotropic effect may be independent of extracellular Ca(2+).

Amino Acid Sequence↗

Effects of various antihypertensive drugs on the function of osteoblast.

Several studies have suggested that high blood pressure is associated with the risk of bone loss. Since various antihypertensive drugs are in wide use for the treatment of hypertension, it is important to investigate the influences of these drugs on bone metabolism. Osteoblasts play a pivotal role in the regulation of bone formation. During differentiation, they sequentially express type I collagen, alkaline phosphatase (ALP), other bone matrix proteins, and finally undergo mineral deposition. In this study, we examined the effects of various antihypertensive drugs on the function of osteoblast using clonal MC3T3-E1 cells. Drugs examined include dihydropyridine-type calcium channel blockers (benidipine, amlodipine, and nifedipine), angiotensin-converting enzyme (ACE) inhibitors (captopril, lisinopril, and enalapril), and angiotensin II receptor type1 (AT1) antagonists (TCV-116 and KW-3433). None of the ACE inhibitors or AT1 antagonists affected ALP activity or cellular DNA content significantly. In contrast, benidipine, amlodipine, and nifedipine increased ALP activity when used in amounts 1 pM, 100 nM, and 100 nM, respectively. Benidipine blocked calcium influx through the L-type voltage dependent calcium channel of MC3T3-E1 more potently than amlodipine or nifedipine. These calcium channel blockers did not change collagen accumulation. Benidipine significantly increased in vitro mineralization at a concentration of 1 nM and higher, while amlodipine did so at 1 microM and nifedipine did not. Comparison of the effective concentration of each calcium channel blocker in our study with the reported maximum serum concentration of each drug suggests that benidipine, but not amlodipine or nifedipine, promotes mineral deposition in human.

3T3 Cells↗

Expanded-bed protein refolding using a solid-phase artificial chaperone.

An efficient solid-phase protein refolding method based on artificial chaperone-assisted refolding is proposed. The method employs insoluble cyclodextrin polymer beads and the expanded-bed technique. Alpha-glucosidase, whose spontaneous refolding yield from a urea-denatured state is up to 30% at a protein concentration of up to 10 microg/ml, could be refolded with a yield that was improved more than two-fold at a protein concentration more than five-fold higher when protein solution was circulated through an expanded bed under optimized conditions. Unlike the conventional liquid-phase artificial system, further steps to purify the refolded product, which are generally needed to remove detergent-cyclodextrin complex and excess cyclodextrin, were unnecessary. In addition, the polymer beads were reusable after simple washing with water, and the continuous system is suitable for easy-scale-up using commercially available devices. This new method is considered to be a powerful means of achieving large-scale protein refolding for industrial protein production.

Journal Article↗

Development of severe longitudinal atrophy of thoracic spinal cord following lupus-related myelitis.

A 26-year-old woman suffered from acute myelitis at Th 6 level associated with systemic lupus erythematosus. Methyl-prednisolone pulse therapy, intravenous high-dose immunoglobulin administration and plasmapheresis were not effective. Her neurological signs had persisted in spite of subsequent administration of oral prednisolone and azathiopurine. Magnetic resonance imaging (MRI) of spinal cord at the onset showed a marked swelling with intramedullary high intensity signals on T2WI along the whole thoracic cord. Three years later, MRI demonstrated a severe longitudinal and segmental atrophy of the mid to low thoracic cord which resulted in transverse spinal signs.

Adult↗

Native valve salvage for post-traumatic tricuspid regurgitation.

We describe two cases of successful management by native valve salvage of an uncommon tricuspid valve regurgitation following blunt chest trauma. The two patients were diagnosed 13 years and six years, respectively, after the trauma. In both cases, tricuspid valvular insufficiency was caused by anterior leaflet prolapse due to chordal and papillary muscle rupture associated with annular dilatation. Operative repair with implantation of artificial chordae, papillary muscle reinsertion and ring annuloplasty resulted in complete recovery. The need for increased awareness of this lesion in patients suffering blunt chest trauma is emphasized, and the relevant literature reviewed.

Adult↗

[Convulsion following the combination of single preoperative oral administration of enoxacine and single postoperative intravenous administration of flurbiprofen axetil].

We experienced a case of convulsion following the combination of single oral administration of enoxacine before an emergency operation and single postoperative intravenous administration of flurbiprofen axetil. The patient was an 87-year-old female referred to our hospital for severe abdominal pain. She was diagnosed as having the strangulation ileus, then underwent the emergent operation of partial resection of the necrotic small intestine under general anesthesia. Unfortunately we did not know that she had temporarily received oral enoxacine 200 mg, a new quinolone, administered by the previous doctor on the day before the operation. After the operation, flurbiprofen axetil 50 mg, a nonsteroidal anti-inflammatory drug, was given intravenously in thirty seconds due to postoperative pain. One minute after administration of the drug, she immediately developed a convulsive fit, severe disturbance of consciousness and apnea. We then administered at once, a single dose of diazepam intravenously for convulsion treatment, kept her airway open and controlled her ventilation. Convulsion disappeared in a minute and her condition improved gradually. We suspect that convulsive seizure may have been induced by the drug interaction between single oral dose of enoxacine before the operation and single intravenous dose of flurbiprofen axetil after the operation. We also suspect that the serum concentration of enoxacine was kept high because of metabolic disturbance and renal dysfunction resulting from her old age and dehydration. This case suggests that medication before the emergency operation must be considered in anesthetic management because of the possible side effect such as convulsion induced by the drug interaction between neuquinolones and anti-inflammatory drugs.

Administration, Oral↗

[Treatment with stellate ganglion block, continuous epidural block and ulnar nerve block of a patient with postherpetic neuralgia who developed complex regional pain syndrome (CRPS)].

We present a case of a 46-year-old female patient with systemic lupus erythematosus who developed herpes zoster of the right eighth cervical nerve. Her whole right forearm, hand and the first through fifth fingers were coated with some gel and protected against pain. She had been suffering from continuous and spasmodic burning pain, hyperalgesia, allodynia, drop in skin temperature, sudmotor disturbance, edema, constructure of the joints, muscle atrophy and bone atrophy of her right upper extremity probably due to postherpetic neuralgia (PHN) associated with complex regional pain syndrome (CRPS). She received right stellate ganglion block (SGB), continuous cervical epidural block and right ulnar nerve block. Reduction of pain and edema as well as improvement in mobility of each joint of her right upper extremity was observed. We suspect that SGB, continuous cervical epidural block and ulnar nerve block are effective and useful alternative treatments in a patient with PHN associated with CRPS of the eighth cervical nerve.

Analgesia, Epidural↗

[Usefulness of epidural infusion of ketamine for relief of localized superficial pain].

Three patients with localized superficial pain had their pain alleviated by single epidural infusion with low dose ketamine. The patients are as follows: a 62-year-old female with herpetic neuralgia on her right sixth thoracic nerve area; a 52-year-old male whose left shoulder, anterior chest and abdomen had been burned by acetylene gas; and a 49-year-old male whose bilateral hands suffering from frostbite by propane gas. Epidural tube insertion to administer a single dose of 10 mg ketamine with lidocaine or bupibacaine was performed in all the three patients. They were administered single epidural infusion of 10 mg ketamine with lidocaine or bupibacaine everyday and they continued to receive epidural block with lidocaine or bupivacaine including buprenorphine or morphine. Therefore, we suspect that single epidural infusion of ketamine, an antagonist for N-methyl-D-aspartic acid receptor, could be an effective and useful alternative treatment in patients with various refractory localized superficial pain of either acute or chronic nature.

Analgesia, Epidural↗

[Stump pain relieved by continuous intravenous ketamine infusion therapy].

We experienced a case of stump pain relieved by continuous intravenous ketamine infusion therapy. A 59-year-old male had his left first through fourth toes amputated because a giant iron plate at work fell on his left foot fifteen years ago. Thereafter he had refractory spontaneous burning pain and night pain on his stump. On examination, we found his left foot skin hard, lustrous, and with sweating disturbance, allodynia and hyperpathia. As intravenous administrations of ketamine 10 mg and thiamylal 50 mg were positive as a drug challenge test, we performed intravenous ketamine infusion at 1 mg.kg-1.hr-1 for 1 hour and a half. After this treatment, his visual analogue scale (VAS) improved dramatically to 0 mm, and night pain, allodynia and hyperpathia disappeared for three days. Thereafter stump pain was relieved to the level of VAS 20 mm. Therefore we diagnosed his stump pain as central pain of neuropathic origin. We suspect that continuous intravenous infusion of ketamine, a noncompetitive blocker of N-methyl-D-aspartic acid receptor, might be an effective and useful alternative treatment in a patient with refractory stump pain.

Excitatory Amino Acid Antagonists↗

[Usefulness of epidural administration of ketamine for relief of postherpetic neuralgia].

Four patients with postherpetic neuralgia had their pain alleviated by epidural administration of ketamine. No oral non-steroidal anti-inflammatory drugs and anti-depressant drugs were effective in all cases. Lidocaine or bupivacaine was administered epidurally to all four patients. When these patients stated that they did not feel pain reduced, they received epidural infusion of ketamine at doses from 5 mg to 20 mg with lidocaine or bupivacaine and their postherpetic neuralgia was controlled. Therefore with these cases, we suspect that epidural administration of ketamine, an antagonist for N-methyl-D-aspartic acid receptor, could be an effective and useful alternative treatment in a patient with refractory postherpetic neuralgia.

Aged↗

[Anesthetic management of a patient with von Recklinghausen disease complicated with spinal tumor and severe spinal deformity].

We had three occasions of giving anesthesia to a patient with von Recklinghausen disease complicated with spinal tumor and spinal deformity. A 49-year-old male patient who had suffered from von Recklinghausen disease since 35 years of age developed slight low respiratory function due to neurofibroma in the spinal canal and the paravertebral lesion and severe kyphoscoliosis in the lumbar spine which were checked by lumbar X-ray, abdominal ultrasonography and computed tomography during the preoperative period. Transurethral biopsy of the bladder tumor, internal urethrotomy for the urethral stricture and vesical lithotripsy for the bladder stone were performed under general anesthesia. Elevated position of his head and lower extremities and slight right lateral decubitus position were employed during anesthetic induction and semi-Trendelenburg's position during anesthetic maintenance. Convalescence after each operation was uneventful. He was comfortable and had a safe perioperative course. He showed no unward change in neurological symptoms during the post-operative period. This case suggests that we must take the complication such as spinal tumor and spinal deformity into consideration for anesthetic management of patients with von Recklinghausen disease and select the appropriate anesthetic method and patient's position.

Anesthesia, General↗

Measurement of structure-dependent K+ --> &mgr;(+)nu(&mgr;)gamma decay

We report the first measurement of a structure-dependent component in the decay K+-->&mgr;(+)nu(&mgr;)gamma. Using the kinematic region where the muon kinetic energy is greater than 137 MeV and the photon energy is greater than 90 MeV, we find that the absolute value of the sum of the vector and axial-vector form factors is |F(V)+F(A)| = 0.165+/-0.007+/-0.011. This corresponds to a branching ratio of B(SD+) = (1.33+/-0.12+/-0.18)x10(-5). We also set the limit -0. 04<F(V)-F(A)<0.24 at 90% C.L.

Journal Article↗

Two novel mutations in the adrenoleukodystrophy gene in two unrelated Japanese families and the long-term effect of bone marrow transplantation.

We identified two novel missense mutations in exon 1 of adrenoleukodystrophy (ALD) gene in two unrelated Japanese families. The first, G(874)C transition results in Arg(163)Pro substitution in the cytoplasmic domain of the ALD protein in adrenomyeloneuropathy family. The second, C(679)G results in Ser(98)Trp substitution in the first transmembrane loop in childhood onset cerebral ALD family. Both mutations cause the substitution of polar amino acid (arginine and serine) with non-polar amino acid (proline and tryptophan). Bone marrow transplantation (BMT) from his non-affected his younger sister was performed on a boy with childhood onset cerebral ALD who showed neurological deficit and brain MRI abnormalities. We evaluated the effect of BMT over a 6-year period in terms of neurological deficit, the level of very-long-chain fatty acids (VLCFA) in plasma and fibroblasts, and brain MRI. After BMT, patient's peripheral white blood cells were replaced by donor's XX ones carrying a normal ALD gene confirmed by in situ hybridization using satellite DNA of the centromere of X and Y chromosomes as probes and the level of VLCFA in lymphocytes was within normal limit. However, his neurological state progressively deteriorated. BMT was not beneficial to him.

Adrenoleukodystrophy↗

Further search for the decay K+-->pi(+)nunu;

A search for additional evidence for the rare kaon decay K+-->pi(+)nunu; has been made with a new data set comparable in sensitivity to the previous exposure that produced a single event. No new events were found in the pion momentum region examined, 211 pi(+)nunu;) = 1.5(+3.4)(-1.2)x10(-10).

Journal Article↗

Direct refolding of recombinant human growth differentiation factor 5 for large-scale production process.

An efficient downstream process for the production of recombinant human growth differentiation factor 5 (rhGDF5) has been developed for industrial application utilizing a novel "direct refolding" method. In this method, the starting material is an inclusion body produced in Escherichia coli, and the critical step is the direct refolding step that follows directly after solubilization of the inclusion body. rhGDF5 can be refolded at a markedly high concentration of 2.4 mg.ml(-1), which is 24 times that hitherto achieved by the proteins of the TGF-beta superfamily. The refolding yield is 63%, and after purification by diafiltration, isoelectric precipitation and reverse-phase chromatography, the final purification yield is 20% with purity higher than 99%. The yield is more than twice that of a conventionally established process having three chromatography steps and the purity is equivalent. The first pilot-scale trial shows a refolding yield of 51% and a final yield of 11%. The final yield is 1.4 times that of the conventional process, and further optimization at pilot-scale is expected to bring this figure up to or above that of laboratory-scale. As a result, the calculated production cost of rhGDF5 has been reduced dramatically. This type of efficient and simple process is beneficial particularly in the large-scale production of recombinant proteins in which high yield and quality are required.

Journal Article↗

Cytoreductive surgery with liver-involved renal cell carcinoma.

The purpose of this study was to demonstrate the benefits of cytoreductive surgery for renal cell carcinomas that also involve the liver. Between 1994 and 1997, four patients with renal cell carcinoma with liver involvement were surgically treated with nephrectomy and hepatectomy. Two of them underwent a simultaneous hepatectomy and nephrectomy (group 1), and the remaining two patients underwent a hepatectomy after a nephrectomy and had a diagnosis of postoperative recurrence (group 2). Two patients, one from each group, died of multiple bone metastasis and lung metastasis 30 months and 12 months after the hepatectomy; the second patient from group 1 died 40 months after the first operation due to gastrointestinal hemorrhaging. The second patient from group 2 displayed no evidence of recurrence 18 months after the second surgical procedure. The survival rates for these patients were 66% and 33% at 1 and 3 years, respectively. Autopsy studies revealed that one patient from group 2 had a local recurrence in the liver while the other two patients from group 1 did not. Our results suggested that a progressive approach may therefore be useful for patients demonstrating renal cell carcinoma where there is liver involvement.

Carcinoma, Renal Cell↗

Identification of protein disulfide isomerase as a phorbol ester-binding protein.

A specific binding protein for 12-O-tetradecanoylphorbol 13-acetate (TPA), different from protein kinase C (PKC) and histone H1, was purified from HeLa cell extract by the use of affinity gel pendanted with phorbol ester (TPA-GEL). The purified binding protein was identified as protein disulfide isomerase (PDI, EC 5.4.3.1) by peptide sequence analysis. The dissociation constants (Kd's) of TPA to PDI, histone H1 and PKCalpha were determined to be 1.03 x 10(-6) M, 5.70 x 10(-7) M, and 4.00 x 10(-7) m, respectively, by the surface plasmon resonance (SPR) method. TPA moderately inhibited PDI activity assessed in terms of reactivation of denatured RNase A.

Amino Acid Sequence↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 26). Detection of 1,3-dinitrobenzene-induced histopathological changes in testes and epididymides of rats with 2-week daily repeated dosing.

As part of a collaborative work, male rats were administered 1,3-dinitrobenzene (1,3-DNB) daily at 0, 25 and 50 mg/kg/day from the age of 6 weeks for 4 weeks (4-week exp.), or at 25, 50 and 75 mg/kg/day from the age of 8 weeks for 2 weeks (2-week exp.). After the end of each administration period, all survivors were sacrificed, and their testes and epididymides were removed, weighed and examined histopathologically. The following results were obtained. In the 4-week exp.: At 50 mg/kg/day, the weights of testes and epididymides showed decrease with macroscopic atrophy. The testicular spermatogenic epithelium showed decrease in the number of sperm-spermatocytes, degeneration/necrosis, giant cell formation and vacuolation, reduction in sperm counts also being evident in the ducts of the epididymides. In the 2-week exp.: At 50 and 75 mg/kg/day, the weights of testes and/or epididymides showed decrease with macroscopic atrophy. Several histopathological changes in the testes and epididymides were essentially the same changes as in the group given 50 mg/kg/day in the 4-week exp., with a clear relation. These results indicate that a 2-week administration period is sufficient to detect testicular and epididymal histopathological changes induced by 1,3-dinitrobenzene in male rats.

Administration, Oral↗