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Biomedical subjects

M Ohtani

Publications and source records attributed to M Ohtani.

At least 91 records · Page 5Linked to original sources

Peptides controlling stifness of connective tissue in sea cucumbers.

We present the first evidence of a system of four bioactive peptides that affect the stiffness of sea cucumber dermis. The body wall dermis of sea cucumbers consists of catch connective tissue that is characterized by quick and drastic stiffness changes under nervous control. The peptides were isolated from the body wall, their amino acid sequences determined, and identical peptides synthesized. Two peptides, which we named holokinins, are homologous with bradykinin. We tested the effect of the peptides on the mechanical properties of sea cucumber dermis. Both of the holokinins softened the dermis, and a pentapeptide that we designated as NGIWYamide stiffened it. Both effects were reversibly suppressed by anesthesia with menthol. We called the fourth peptide stichopin; it had no direct effect on the stiffness of the dermis but suppressed action of the neurotransmitter acetylcholine reversibly. The results suggest that the peptides are neuropeptides and are part of a sophisticated system of neurotransmitters and neuromodulators that controls the connective tissue stiffness of sea cucumber dermis.

Amino Acid Sequence↗

Absorbability of calcium from a new calcium supplement prepared from bovine marrow-free bone in rats.

Powdered bovine marrow-free bone was completely solubilized with lactic and citric acids under reduced pressure. The resulting solution was lyophilized to obtain a stable powder form (total bone extract, TBE), and the calcium (Ca) absorbability of TBE from intestine was investigated in normal rats. Each animal perorally received 10 mg of Ca in 1 mL of distilled water as extrinsic 45Ca-labeled TBE, intrinsic 45Ca-labeled Ca lactate, or intrinsic 45Ca-labeled Ca carbonate. The amount of radioactivity in plasma was measured periodically up to 34 h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximal 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUC infinity) and the radioactivity at Tmax (Cmax) values for the TBE group were significantly higher than those of the Ca carbonate group. Similar results were observed between the Ca lactate and the Ca carbonate groups. No significant difference was observed in the AUC infinity and the Cmax values between the TBE and the Ca lactate groups. Radioactivity in a femur 34 h after dosing was highest in the Ca lactate group and lowest in the Ca carbonate group among the three groups. Both the TBE and the Ca lactate groups showed significant higher whole-body 45Ca retention than the Ca carbonate group did, although no significant difference was found between the TBE and the Ca lactate groups. These findings indicate that the Ca absorbability of TBE is almost comparable with that of Ca lactate and higher than that of Ca carbonate. Therefore TBE would be useful as a Ca supplement with relatively high absorbability from intestine.

Animals↗

Prognostic value of tumor cell proliferation and intratumor microvessel density in advanced gastric cancer treated with curative surgery.

To clarify the prognostic value of tumor cell proliferation [proliferating cell nuclear antigen (PCNA)-positive rate assessed by anti-PCNA immunostaining] and intratumor microvessel density (/0.74 mm2, assessed by anti-CD34 immunostaining) in gastric cancer, 192 advanced gastric cancer patients who underwent curative surgery were investigated. Multivariate analysis showed that the following variables were significantly related to prognosis: age (P=0.029), depth of invasion (P=0.005), lymph node metastasis (P=0.006), lymphatic invasion (P=0.038), venous invasion (P=0.0005), PCNA-positive rate (P=0.049) and intratumor microvessel density (P=0. 011). In conclusion, tumor cell proliferation and intratumor microvessel density were independent prognostic factors in patients with advanced gastric cancer undergoing curative surgery.

Adult↗

A novel D-amino-acid-containing peptide isolated from Aplysia heart.

A novel cardio-excitatory peptide was purified from the hearts of Aplysia kurodai. The peptide was a tripeptide containing a D-amino acid residue in the second position, Asn-D-Trp-Phe-NH2 (NdWFamide). NdWFamide increased the amplitude of contractions of the perfused Aplysia heart with little effect on beating frequency, showing a threshold of approximately 10(-11) M. The peptide also potentiated spontaneous contractions of the anterior aorta. The synthetic peptide having L-Trp instead of D-Trp was about 1,000 times less potent than the native one. NdWFamide seems to play an important role in regulation of cardiac activity in Aplysia.

Animals↗

Synthesis and evaluation of novel fluorinated methotrexate derivatives for application to rheumatoid arthritis treatment.

An ongoing search for new antifolate drugs useful against rheumatoid arthritis (RA) led us to prepare new methotrexate (MTX) derivatives containing enantiomerically pure L-erythro- or L-threo-gamma-fluoroglutamic acid. The derivatives in which the phenyl ring was replaced by a 3'-substituted phenyl or methylthiophene ring showed potent immunosuppressive activities, including in vitro inhibition of mitogen responses to both T and B cells and in vivo inhibition of antibody production in mice. These compounds also exhibited inhibitory activity in adjuvant arthritis in rats. Their toxicity was lower than that of MTX, which was probably due to the strong electronegativity of fluorine, which increases the acidity of the gamma-carboxyl group and thereby decreases polyglutamylation in normal cells. These results revealed the potential of the fluorinated MTX derivatives as candidate drugs for the treatment of RA.

Animals↗

Therapeutic experience of venomous snakebites by the Japanese viper (Agkistrodon halys Blomhoffii) with low dose of antivenin: report of 43 consecutive cases.

Forty-three consecutive patients of venomous snakebite by the Japanese viper (Agkistrodon halys Blomhoffii, "Mamushi" in Japanese) were treated with an uniformly scheduled therapy from 1990 and 1994. The therapy was mainly composed of minimal dose of antivenin, methylprednisolon and cepharanthin. There were two clinical courses, i.e., the minimal envenomation course (Group A, n = 14) and the severe one (Group B, n = 29). Our treatment was so satisfactory that all patients of both groups fully recovered activities of daily living with neither organic disorders nor sequelae of the bitten extremities. The high appearance ratio of atypical lymphocytes (P < 0.05) and the increased ratio of lymphocyte count to White blood cell count (P < 0.02) could be indicators that predict which clinical courses the patients take.

Adolescent↗

Isolation of bioactive compounds from Helix aspersa nerve tissue and the effect of pQPPLPRYamide on heart, esophagus and central neurons of H. aspersa and rectum of Anodonta woodiana.

1. Both acetone and methanol extraction was used to isolate bioactive compounds from 1000 Helix aspersa brains. 2. Seven compounds were isolated of which four were identified as follows: Ha-1, 5-hydroxytryptamine; Ha-3, GSPYFVamide; Ha-4, pQPPLPRYamide; Ha-5, SGYLAFPRMamide. There was insufficient material to identify Ha-2, Ha-6 and Ha-7. 3. Ha-4, pQPPLPRYamide, was found to excite the heart of H. aspersa, relax the esophagus and both excite (mainly) and inhibit central neurons. In addition, this peptide contracted the rectum of Anodonta woodiana. 4. It is concluded that pQPPLPRYamide is an example of a new molluscan peptide family, designated as PRYamide.

Animals↗

Evaluation of cerebral hemodynamics in a head-injured patient with hypovolemia using transcranial Doppler sonography.

A 20-year-old man presented with hypovolemic shock caused by abdominal injury. Cerebral hemodynamics were evaluated by transcranial Doppler (TCD) sonography. Middle cerebral artery flow velocities decreased, and the pulsatility indices increased markedly. Particularly, the waveform of the left middle cerebral artery showed a systolic peak, suggesting an increased intracranial pressure. Actual intracranial pressure was 7 mm Hg, and the cerebral perfusion pressure (CPP) was 51 mm Hg. These abnormal Doppler signals seemed to be caused by a compromise in CPP and to be aggravated by hypovolemia. The patient was discharged with a residual mild memory disturbance. Hypovolemia aggravates a reduced cerebral blood flow caused by a compromised CPP, and the waveform of TCD in a case of hypovolemic shock should be differentiated from intracranial hypertension.

Accidents, Traffic↗

Assessment of myocardial distribution of retrograde and antegrade cardioplegic solution in the same patients.

OBJECTIVE: In order to clarify intramyocardial delivery and distribution of retrograde cardioplegic solution in humans, we induced both ante- and retrograde methods in the same patients to compare their respective delivery and distribution using myocardial contrast echocardiography during surgery. METHODS: 15 patients consisting of nine patients with valvular heart diseases and six patients with coronary artery diseases (including two patients with myocardial infarcted areas and two patients with areas supplied by coronary collateral situation associated with totally occluded coronary arteries without myocardial infarction). Induction of cardioplegia was initially accomplished antegradely and thereafter retrogradely. RESULTS: In valvular heart disease, retrograde cardioplegic solution was distributed less homogeneously, and was not delivered to the midportion of the interventricular septum in two-thirds of the patients (6/9). The transmural myocardial distribution in the anterior, lateral, and posterior walls in the left ventricle were similar for both ante- and retrograde cardioplegic solution, while delivery to the endocardial halves was better than to the epicardial halves (endo-/epicardial intensity ration in antegrade versus retrograde: 1.31 +/- 0.24 versus 1.29 +/- 0.26; 1.19 +/- 0.05 versus 1.36 +/- 0.23; 1.33 +/- 0.28 versus 1.44 +/- 0.35, respectively (all NS)). For delivery to the right ventricle, the existence of small cardiac vein was important. In patients with small cardiac vein (34% in our study), the delivery to the right ventricular dorsal walls was shown. In coronary heart disease, retrograde cardioplegic solution was well delivered to the areas by coronary collateral situation associated with totally occluded coronary arteries, but antegrade solution was not. Neither ante- nor retro grade solution was delivered to myocardial infarcted areas. CONCLUSIONS: These results have important implications for planning strategies for myocardial protection. We think that it is necessary to fully grasp the coronary arterial and venous anatomy of individual patients and to know how to use either ante- or retrograde cardioplegia properly.

Aged↗

Visualization of tumor vessels in hepatocellular carcinoma. Power Doppler compared with color Doppler and angiography.

PURPOSE: To assess the visualization of tumor vessels in hepatocellular carcinoma (HCC) by power Doppler sonography. MATERIAL AND METHODS: We examined 40 patients with 47 HCC lesions by means of power Doppler sonography and compared its visualization of tumor vessels with those of color Doppler and angiography. RESULTS: In 38 (81%) of the 47 lesions, power Doppler sonography improved the visualization of tumor vessels compared with color Doppler sonography; in the remaining lesions no significant difference was noted. In lesions located within 7 cm in depth, there was no significant difference between power Doppler sonography and angiography. In 10 (83%) out of 12 small (< or = 2 cm in diameter) lesions and in 11 (85%) out of 13 hypovascular lesions, power Doppler sonography performed considerably better than angiography. In deeper-seated lesions, however, angiography was significantly superior to power Doppler sonography. CONCLUSION: Power Doppler sonography is more sensitive in detecting the fine tumor vessels in most HCCs than color Doppler sonography. In addition, power Doppler sonography can replace angiography in evaluating tumor vascularity in HCCs except in lesions that are deep-seated or located near the heart. In these lesions, angiography can complement power Doppler sonography in demonstrating tumor vessels.

Aged↗

Delayed hyperemia causing intracranial hypertension after cardiopulmonary resuscitation.

OBJECTIVE: To clarify whether early or delayed failure of cerebral perfusion after cardiopulmonary resuscitation (CPR) occurs in humans and contributes to secondary brain damage. DESIGN: Prospective, repeated-measures study. SETTING: Intensive care unit of Hiroshima University School of Medicine. PATIENTS: Eight comatose patients who had undergone successful resuscitation from cardiac arrest. INTERVENTIONS: All patients underwent transcranial Doppler sonography examination. The intracranial cerebral pressure (ICP) and jugular venous oxygen saturation (SO2) also were continuously monitored in five patients and three patients, respectively. MEASUREMENTS AND MAIN RESULTS: In each patient, we measured the mean flow velocity of the middle cerebral artery transcranially and the mean flow velocity of the internal carotid artery, high in the neck, using transcranial Doppler sonography. The pulsatility index for each measurement was also calculated. The first examinations were performed within 4 to 12 hrs of CPR, and repeat examinations were performed approximately every 12 hrs. The initial mean flow velocities of the middle cerebral artery and the initial mean flow velocities of the internal carotid artery were relatively low, with relatively high pulsatility indices. The mean flow velocities of the middle cerebral artery began to increase at 12 to 24 hrs after CPR and peaked 24 to 120 hrs after CPR. A simultaneous increase in mean flow velocities of the internal carotid artery was observed during this period. The pulsatility index in both arteries dropped significantly during peak mean flow velocity of the middle cerebral artery. In six of seven patients with an abnormal increase (> 100 cm/ sec) in peak mean flow velocity of the middle cerebral artery, the ratio of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery was < 3. This value tended to be lower in patients with poor outcomes. An increased mean flow velocity of the middle cerebral artery, with a ratio of < 3 for mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery, was defined as hyperemia. Although the mean flow velocity of the internal carotid artery was not measured, another patient with an abnormal increase in mean flow velocity of the middle cerebral artery revealed a high jugular venous SO2 value of 83.5%, also representing hyperemia. All ICP values were within the normal range 4 to 12 hrs after CPR and tended to increase before peak mean flow velocity of the middle cerebral artery. The two patients with the lowest ratios of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery showed significant increases in ICP after the peak mean flow velocity of the middle cerebral artery. These two patients subsequently developed brain death. CONCLUSIONS: Delayed hyperemia occurs in humans after resuscitation from cardiac arrest. Our data suggest that this delayed hyperemia can lead to intracranial hypertension and occasionally acute brain swelling, contributing to a poor outcome. A high mean flow velocity of the middle cerebral artery with a low ratio of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery may be predictive of critical hyperemia. As an indirect method of measuring cerebral blood flow transcranial Doppler sonography can be used to adjust treatment for failure of cerebral perfusion after resuscitation.

Blood Flow Velocity↗

Cerebral fat embolism studied by magnetic resonance imaging, transcranial Doppler sonography, and single photon emission computed tomography: case report.

Cerebral fat embolism syndrome is an uncommon complication of trauma. We present a patient who developed cerebral fat embolism syndrome secondary to long-bone fractures. Although computed tomography of the brain failed to show any intracranial lesion, magnetic resonance imaging (MRI) detected scattered, high-signal-intensity lesions on T2-weighted images. 99mTc-d, 1-hexamethyl-propylene amine oxine single photon emission computed tomography (99mTc-HMPAO SPECT) and transcranial Doppler sonography (TCD) demonstrated low cerebral blood flow in the acute stage. MRI, 99mTc-HMPAO SPECT, and TCD correlated well with the clinical course of cerebral fat embolism syndrome.

Adult↗

Clinical evaluation of nuclear matrix protein 22 (NMP22) in urine as a novel marker for urothelial cancer.

OBJECTIVES: This study was undertaken to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a novel urine marker for urothelial cancer, particularly, to substitute for voided-urine cytology. METHODS: NMP22 values were determined for 280 patients and 20 healthy volunteers by NMP22 Test Kit based on an enzyme-linked immunosorbent assay. RESULTS: When the cut-off value was set at 10 U/ml, the positive rate of urinary NMP22 for urothelial cancer was 80.9% (38/47), whereas that for posttreatment cases and benign diseases was 35.7% (74/207). When urinary NMP22 and voided-urine cytology were compared, the test for urinary NMP22 showed higher sensitivity than cytology in patients with urothelial cancer. When urinary NMP22 values were determined pre- and postoperatively in patients with urothelial cancer, the postoperative value decreased in all patients, and were below the cut-off value in all except one patient. CONCLUSIONS: Urinary NMP22 is a useful diagnostic marker as a substitute for voided-urine cytology for the surveillance of urothelial cancer.

Adenocarcinoma↗

Prostaglandin F2 alpha promotes the inhibitory action of endothelin-1 on the bovine luteal function in vitro.

Prostaglandin F2 alpha (PGF2 alpha) is a primary luteolysin in the cow. Although the mechanisms involved in luteolysis are thought to be a complex of its direct action on luteal cells and indirect effect on luteal blood flow, the detailed mechanisms remain to be elucidated. This study focuses on the possible interaction of endothelial cells-derived endothelin-1 (ET-1) with PGF2 alpha in the rapid suppression of progesterone release from the bovine corpus luteum (CL). In in vitro microdialysis system (MDS) of CL, PGF2 alpha acutely stimulated the release of progesterone and oxytocin during infusion and ET-1 release after infusion. Moreover, PGF2 alpha induced slight decrease of progesterone release during the last period of the experiment (8-11 h after PGF2 alpha exposure). Two 1 h-perfusions of ET-1 at 3 h intervals induced only a slight decrease of progesterone release after the second perfusion. This treatment also affected the oxytocin release; the first ET-1 perfusion produced an acute stimulation, whereas the second ET-1 perfusion inhibited the release to below 50%. When the CL pieces were pre-perfused with PGF2 alpha for 2 h, the two consecutive perfusion of ET-1 at 3 h intervals induced drastic decrease in progesterone and oxytocin release only after the second ET-1 perfusion. Thus, a pre-exposure with PGF2 alpha clearly potentiated the inhibiting activity of ET-1 in the progesterone release. These results suggest a physiological impact of PGF2 alpha and ET-1 in the rapid cascade of functional luteolysis in vivo, and a possible interaction between endothelial cells and luteal cells.

Animals↗

Kinetics of respiratory depression in rats induced by buprenorphine and its metabolite, norbuprenorphine.

The respiratory depression induced by buprenorphine and its active metabolite, norbuprenorphine (NBN), was evaluated in rats by measurement of changes in respiratory rate and arterial pCO2 levels. After i.v. bolus administration of buprenorphine no effects were noted over the dose range 0.008 to 3 mg/kg; by contrast, the respiratory rate after rapid i.v. administration of NBN decreased in a dose-dependent fashion within the dose range of 1 to 3 mg/kg, and the arterial pCO2 levels also varied in relation to the change in respiratory rate. The minimum respiratory rate was observed 15 min after NBN administration. Judging by the respiratory depressive effect after i.v. infusion, NBN was approximately 10 times more potent than the parent drug. In spite of the similarity of NBN concentrations in the brain after i.a. and after i.v. administration of NBN (3 mg/kg), neither the respiratory rate nor the arterial pCO2 levels after i.a. administration changed compared with the control levels. Moreover, the NBN concentration in the lungs after i.v. administration was approximately 4-fold higher than that after i.a. administration. NBN-induced depression was rapidly reduced after i.v. administration of naloxone and beta-funaltrexamine, but ICI 174864 was without effect. These results suggest that the respiratory depression induced by NBN may be mediated by opioid mu receptors in the lung rather than in the brain.

Analgesics, Opioid↗

[Radiological diagnosis of viral encephalitis].

Most of viral encephalitis may demonstrate no specific change on CT and MR images. Brain swelling, edema, abnormal density (CT) and abnormal intensity (MR) can be detected in herpes simplex encephalitis and enterovirus encephalitis (coxsackie, echo, polio). The common finding on CT and MRI in patients with HIV encephalopathy are atrophy, leukomalacia. Progressive multifocal leukoencephalopathy (PML) shows multifocal oval or round white matter T2-hyperintensities on MR images. Subacute sclerosing panencephalitis (SSPE) may present slight changes in the subcortical and periventricular white matter, as well as basal ganglia. Progressive disorder makes widespread T1-low, T2-high intensity area and atrophy. MRI of acute disseminated encephalomyelitis (ADEM) shows multifocal subcortical hyper intense foci on T2-weighted studies. The deep white matter, brainstem, thalamus and cerebellum can be affected. Most of ADEM lesions resolve. Imaging findings of acute lymphocytic meningitis by echovirus and coxsackievirus are usually normal.

Encephalitis, Viral↗

[Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker for urothelial cancer--NMP22 as a urinary marker for surveillance of bladder cancer. NMP22 Study Group].

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the surveillance of bladder cancer, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 144 patients with histologically diagnosed bladder cancer, 65 patients with other urological cancers, and 171 healthy volunteers by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All bladder cancer patients were evaluated for urinary NMP22 values and voided urine cytology simultaneously from the same urine samples. Based on the data from the bladder cancer patients and the healthy volunteers, the cut-off value was set at 12 U/ml. The median urinary NMP22 value for the bladder cancer patients was 17.8 U/ml (95% CI: 13.1-29.0). The sensitivities of urinary NMP22 and voided urine cytology were 61.1% (88/144) and 33.8% (48/144), respectively, a significant difference (p < 0.00001). Multivariate analysis revealed that tumor size affected the urinary NMP22 values. The positive rate by tumor size was 42.3%, 59.1%, and 85.0% for tumors of < 10 mm, 10-30 mm, and > 30 mm, respectively. Urinary NMP22 values decreased postoperatively in 82.9% of the patients. The median NMP22 values for prostate cancer and renal cancer were 4.4 U/ml (95% CI: 2.2-6.7) and 6.2 U/ml (95% CI: 3.6-12.5). The positive rates were 24.2% and 31.3%, respectively, both of which were significantly lower than for bladder cancer. Our multicenter study indicates that urinary NMP22 test is more sensitive than voided urine cytology test for the surveillance of bladder cancer.

Adult↗