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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 55 records · Page 3Linked to original sources

Evidence for the AT1 subtype of the angiotensin II receptor in the rat submandibular gland.

We have characterized angiotensin II (Ang II) receptor subtypes on rat submandibular gland membranes using a radioligand binding assay. [3H]Ang II binding to the membrane fractions exhibited both high (Kd =0.08 nm, Bmax =2.19 fmol/mg protein) and low (Kd =4.19 nm, Bmax = 13.7 fmol/mg protein) affinity. Ang 11, Ang III and saralasin completely displaced the [3H]Ang II binding, whereas CV-11974, an AT1 receptor antagonist and PD123319, an AT2 receptor antagonist maximally displaced up to approximately 87 and 13% of the total binding, respectively. [3H]DuP753 binding to the membrane fractions exhibited a single population of binding site with a Kd of 4.22 nM and Bmax of 3.77 pmol/mg protein. Ang II, Ang III and CV-11974 completely displaced the [3H]DuP753 binding with slope factors near unity, but PD123319 did not. These findings suggest that rat submandibular gland membranes contain predominantly the AT1 receptor subtype.

Angiotensin Receptor Antagonists↗

Formation of spherical micelles by the novel platelet activating factor receptor antagonist, E5880.

E5880, a novel platelet activating factor receptor antagonist, was dispersed in water for the preparation of injectable formulation and the physicochemical properties of the micelles were characterized. The critical concentration for formation of micelles was 0.12 mM. Using the area per molecule results, the critical packing parameter was calculated and showed that the structure was composed of spherical micelles and the number of the molecules per micelle was 88. The diameter of a micelle was 8.1 nm. The fluidity and micropolarity around the hydrocarbon region of the micelles were evaluated and compared to the surfactants, stearyltrimethylammmonium chloride and cetyltrimethylammonium chloride.

Lipids↗

Asymmetric reduction of ethyl 2-methyl e-oxobutanoate by fungi.

Seven fungi, which are found to reduce ethyl 3-oxobutanoate in high yields, were tested for their reducing ability for ethyl 2-methyl 3-oxobutanoate. We obtained some interesting findings. In particular, Penicillium purpurogenum reduced ethyl 2-methyl 3-oxobutanoate to the corresponding alcohols with the diastereomer (anti/syn) ratio of 93/7 with the enantiomeric excess of anti-(2S,3S)- and syn-(2S,3R)- hydroxy esters of 90 and >99 ee%, respectively.

Aspergillus↗

Lymph-node staining with activated carbon CH40: a new method for axillary lymph-node dissection in breast cancer.

OBJECTIVE: To demonstrate the usefulness of activated carbon particles (CH40) as a vital staining dye for visualizing lymphatic vessels and lymph nodes in breast cancer. DESIGN: A retrospective evaluation. SETTING: Department of Surgery in Sendai National Hospital, Japan, a 716-bed teaching hospital. METHODS: To identify as many lymph nodes as possible in the axillary fat, by which we might decrease the possibility of the presence of undetected metastatic nodes, an emulsion of activated carbon particles (CH40) was injected into the centre of the mammary gland, close to the tumour site, 3 days before radical surgery. MAIN OUTCOME MEASURE: The number of lymph nodes found by the traditional method and by the CH40-injection method were recorded. RESULTS: After injection, the CH40 was readily adsorbed into regional lymphatics and streamed along with the lymph flow to blacken regional lymph nodes. The CH40-guided method increased the mean number of nodes per case found in the axilla from 8.4, by the traditional method, to 14.0 nodes per case. CONCLUSIONS: The use of the CH40 technique has two technical advantages; one is that it allows surgeons to locate the blackened lymph nodes at the time of surgery and the other is that it allows pathologists to look for the nodes in fatty tissue. Lymph-node dissection with the aid of activated carbon particles is inexpensive, easy to perform and enables the smallest lymph nodes to be easily recognized. CH40 is the technique of choice for the detection of axillary lymph nodes in cases where the number of lymph nodes detected by the traditional method is too small for accurate surgery. In conclusion, the present study demonstrates that CH40 could be an appropriate tool for more accurate staging of breast cancer axillary specimens.

Adult↗

Clinicopathologic prognostic factors in patients with Borrmann type 4 gastric cancer: univariate and multivariate analyses.

BACKGROUND: Advanced gastric cancer is classified into four Borrmann types, types 1 to 4. Type 4 is a relatively undifferentiated carcinoma with little or no gland-forming capability. Despite recent advances in the diagnosis and surgical management of gastric cancer, most tumors of Borrmann type 4 are not detected at an early stage and the prognosis remains poor; the five-year survival rate after gastric resection ranges from 10 to 20 percent. We evaluated the affects of several clinicopathologic variables on the 5-year survival rate after resection of Borrmann type 4 gastric cancer. METHODS: Data on clinical characteristics were obtained from the records of patients who underwent gastric resection between 1985 and 1995 at the Department of Surgery, Sendai National Hospital, and follow-up data were obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. The relationship between clinicopathologic variables and 5-year survival rate was estimated by the Kaplan-Meier survival curve and the logrank test. Multivariate Cox's proportional hazards regression analysis was then performed to determine which variables were independent prognostic factors. RESULTS: Eighty-seven patients with Borrmann type 4 gastric cancer underwent a resection during the study period at our hospital. The overall 5-year survival rate was 14.8%. The relationship between clinicopathologic variables and 5-year survival rate was determined by constructing a Kaplan-Meier survival curve. Tumor location (upper, middle and distal vs whole stomach, p=0.0214), lymph node metastasis, capillary microinvasion, and peritonitis carcinomatosa (absent vs present, p<0.05) significantly influenced survival. When multivariate analysis using Cox's proportional hazards regression of 5-year survival was performed, capillary microinvasion, peritonitis carcinomatosa (absent vs present) and tumor location (distal vs whole stomach) emerged as the statistically significant independent prognostic factors associated with long-term survival. CONCLUSION: Capillary microinvasion and the presence or absence of peritonitis carcinomatosa are more powerful predictors of 5-year survival than is lymph node metastasis. Patients with gastric cancer of the whole stomach have a poorer prognosis than do those with carcinoma in the antrum of the stomach.

Adult↗

Technetium-99m complex of N-(2-pyridylmethyl)iminodiacetic acid as a new renal radiopharmaceutical.

A tetradentate chelating agent constituting of an iminodiacetic acid group and a nitrogen atom of pyridine, N-(2-pyridylmethyl)iminodiacetic acid (PMIDA), was coordinated with 99mTc and evaluated as a renal functional agent. The complex of PMIDA with 99mTc was prepared by using a stannous chloride solution as a reducing agent. The chelating efficiency was analyzed by thin layer chromatography and electrophoresis. Chelation with 99mTc resulted in a single radiochemical product. Biological studies were performed in mice and rats. 99mTc-PMIDA was removed from the circulation solely by the kidneys. Clearance of 99mTc-PMIDA from the blood and the kidneys was as rapid as that of 99mTc-diethylenetriaminepentaacetic acid. The rate of blood clearance was unaffected by the administration of probenecid (a test for tubular secretion by the weak-acid mechanism), so that the glomerular filtration rate could be estimated by measuring its clearance from the blood. The results in animals with myohemoglobinuric acute renal failure suggested that 99mTc-PMIDA might be a useful renal function radiopharmaceutical.

Acute Kidney Injury↗

Different cell cycle mechanisms between UV-induced and X-ray-induced apoptosis in WiDr colorectal carcinoma cells.

Although DNA-damaging agents such as ultraviolet (UV) and X-ray can induce apoptosis, the difference in the apoptotic mechanism is not clearly understood. In the present study, we investigated the effects of these two genotoxic agents on the induction of DNA damage and subsequent apoptotic cell death from the viewpoint of cell cycle regulation by using WiDr cells. Transient G1 arrest was observed after UV exposure, whereas G2 but not G1 arrest was induced after X-ray irradiation. UV-exposure could induce G1 arrest in both mutant-type (mt-p53) and wild-type p53 (wt-p53) cells, but obvious G1 arrest was not observed in the cells lacking in p53 expression. An increase in the DNA fragmentation was observed at S phase in UV-irradiated cells and at G2 phase in X-irradiated cells, respectively. UV-irradiated cells showed an increase production of p53 protein and accumulation of p21 protein. On the contrary, both p53 and p21 proteins remained at a low level in X-irradiated cells. Treatment with aphidicolin, an S phase blocking agent, prolonged cell cycle arrest and reduced the rate of apoptotic cell death in both UV-irradiated and X-irradiated cells. From these results, it is suggested that UV-induced apoptosis occurs mainly at S phase and is regulated by increased production of p53 and p21 proteins, while X-ray-induced apoptosis occurs after G2 blockade and may be independent of p53.

Journal Article↗

Electrophysiological properties of the left atrium evaluated by coronary sinus pacing in patients with atrial fibrillation.

Repetitive atrial firing (RAF), marked fragmentation of atrial activity (FAA), and interatrial conduction delay (CD) have been shown to be electrophysiological features of the atrium in patients with atrial fibrillation (AF). Moreover, it has been observed that atrial extrastimuli are more likely to induce AF when delivered from the right atrial appendage (RAA) than from the distal coronary sinus (CSd). We examined the electrophysiological properties of the atrial muscle by CS and RAA stimulation in patients with paroxysmal AF. Patients were divided into two groups: group I, consisting of 18 patients with clinical paroxysmal AF; and group II, consisting of 22 patients with various cardiac arrhythmias in which the substrate does not exist in the atrium. In group I, the following values of electrophysiological parameters of the atrium indicated that AF was more likely to be induced during RAA pacing than CSd pacing: atrial effective refractory period (RAA vs CSd: 201 +/- 28 ms vs 240 +/- 35 ms, P < 0.001), RAF zone (16 +/- 25 ms vs 0 +/- 0 ms, P < 0.03), FAA zone (38 +/- 37 ms vs 5 +/- 19 ms, P < 0.01), maximum interatrial conduction time (144 +/- 19 ms vs 93 +/- 19 ms, P < 0.0001) and CD zone (53 +/- 21 ms vs 9 +/- 18 ms, P < 0.0001). The values of the electrophysiological parameters of the atrium evaluated by CSd pacing in group I patients were not significantly different from those in group II patients. In conclusion, when coronary sinus stimulation is performed, electrophysiological properties of the atrium in patients with AF show a significant decrease in atrial vulnerability compared to stimulation from RAA and also show similar values to those in patients without AF. It might be suggested that the left posterior or posterolateral atrium is electrophysiologically stable even in patients with paroxysmal AF.

Adult↗

Clinical application of magnetoencephalography in a patient with corticobasal degeneration.

Previous neuroimaging studies in corticobasal degeneration (CBD), such as MRI and positron emission tomography, showed lateralized cortical atrophy and a decrease in cortical oxygen metabolism, respectively. The advantage of magnetoencephalography in the research of the auditory system is that activity of both hemispheres can be detected separately. Auditory-evoked magnetic fields (AEFs) were then applied to a patient with corticobasal degeneration. The strength of N100m equivalent current dipoles (ECD) in left hemisphere was extremely smaller (20 nAm) than that in right hemisphere (48 nAm). This results implies that CBD patient might have a decrease in the number of neurons in the primary auditory cortex. This study suggests that AEF measurement is one of the most powerful tools for detecting latent impairment of auditory function in patients with corticobasal degeneration.

Aged↗

A Chinese traditional medicine, sho-saiko-to (xiao-chaihu-tang), reduces the bioavailability of tolbutamide after oral administration in rats.

The effects of Sho-saiko-to on the pharmacokinetics of tolbutamide were investigated in rats. After intravenous administration of tolbutamide (5 mg/kg), no significant change in the pharmacokinetics of tolbutamide was observed in both groups of single and multiple (7 days) pre-administration of Sho-saiko-to (500 mg/kg). In the study of single oral administration of tolbutamide (50 mg/kg), co-administration of Sho-saiko-to tended to accelerate the initial absorption rate of tolbutamide. The area under the plasma concentration-time curve of tolbutamide after oral administration was significantly reduced by Sho-saiko-to. Subsequently, a significant decrease was observed in the oral bioavailability of this drug when Sho-saiko-to was given concomitantly. These findings suggest that Sho-saiko-to reduces the bioavailability of tolbutamide after oral administration in rats, and that this change is not related to hepatic metabolism.

Algorithms↗

Control of the dispersing process and pharmacokinetics in rats for lipid A analogue, E5531.

E5531 is a synthetic disaccharide analogue of lipid A which has a low toxicity but retains the ability to reduce production of tumour necrosis factor. This analogue has potential for use in the treatment of septic shock. An injectable formulation of E5531 would be useful, but dispersion in aqueous solution is a problem. In the present study the dispersing process for E5531 was evaluated using the pH-jump method (pH 11.0-->7.3). The size of the aggregates was decreased (reaching 20 nm) with increasing dispersing time in 0.003 M NaOH (pH 11.0). The membrane fluidity of the aggregates increased with increasing dispersing time. When prepared by the normal dilution method (pH 7.3-->7.3), the size of the aggregates remained constant at 140 nm and the membrane fluidity was smaller than that of samples prepared by the pH-jump method. This indicates that during dispersing at basic pH, the hydration proceeded in a normal manner, but then stopped, just after adjustment of the pH to 7.3. This suggests that the degree of hydration of the membrane is dependent on the dispersing time at pH 11.0. Using samples with different degrees of hydration and different membrane fluidity prepared by the pH-jump method, the pharmacokinetics and stability of the aggregates were evaluated after intravenous injection into rats. The data thus obtained confirmed that the membrane fluidity was correlated with the pharmacokinetics and stability in rat plasma. It was concluded that the pharmacokinetics of E5531 in rats can be controlled by changing the degree of hydration and membrane fluidity by means of using different dispersing times in alkaline solution (pH 11.0).

Animals↗

Distribution of ciprofloxacin into the central nervous system in rats with acute renal or hepatic failure.

Pharmacokinetic changes of various drugs have been reported in renal or hepatic failure. The present study employed ciprofloxacin, a quinolone antibiotic having neurotoxic side effects, to assess the influence of these diseases on distribution of ciprofloxacin into the central nervous system (CNS). After intravenous dosing of ciprofloxacin (10-30 mg kg(-1)), ciprofloxacin levels in plasma and brain were measured in normal rats (Wistar, male, 10-week-old) and those with acute renal and hepatic injuries which were induced by uranyl nitrate and carbon tetrachloride (CCl4), respectively. In the uranyl nitrate-treated rats, the plasma elimination half-life of ciprofloxacin was prolonged and the total body clearance was reduced when compared with those in the normal rats. Similar but smaller changes were observed in the CCl4-treated group. Brain levels of ciprofloxacin were significantly increased by both uranyl nitrate and CCl4 treatments. A proportional correlation between serum unbound levels and brain levels of ciprofloxacin was observed in the normal group. However, brain-to-serum unbound concentration ratios of ciprofloxacin were reduced in the rats with renal or hepatic failure. These results suggest that renal failure as well as hepatic failure retards elimination of ciprofloxacin from the blood, leading to elevation of the CNS level, and also that ciprofloxacin distribution in the brain is reduced in these disease states.

Animals↗

The effect of the lipid A analog, E5531 on fever induced by endotoxin from Escherichia coli.

E5531 is a specific lipid A antagonist and is expected to be a drug for the treatment of septic shock. The LAL (limulus amebocyte lysate) activity and pyrogenicity of E5531 were determined. The LAL activity of E5531 is large and confirmed that E5531 had a high affinity to the lipopolysaccharide receptor. The pyrogenic activity of E5531 is weak and the pyrogenic profile of E5531 is different from that of USP (United States Pharmacopoeia) reference standard endotoxin (ETX). E5531 suppressed the pyrogenicity of ETX in rabbits, indicating that E5531 is expected to be useful for the treatment of fever induced by ETX.

Analgesics, Non-Narcotic↗

Asymmetric reduction of ethyl 2-methyl 3-oxobutanoate by Chlorella.

Chlorella pyrenoidosa Chick reduced ethyl 2-methyl 3-oxobutanoate to the corresponding alcohols with the diastereomer (anti/syn) ratio of 53/47. The enantiomer excesses of anti-(2S, 3S)- and syn-(2S, 3R)-hydroxy esters were 89 and > 99ee% respectively. C. vulgaris and C. regularis afforded predominantly the syn-isomer, contrary to C. pyrenoidosa. The differences in the activity of reducing ethyl 2-methyl 3-oxobutanoate were observed among three strains of Chlorella. Addition of 2% metal salts slightly increased the chemical yield of the hydroxy ester.

Butyrates↗

Disulfide formation in bovine zona pellucida glycoproteins during fertilization: evidence for the involvement of cystine cross-linkages in hardening of the zona pellucida.

The time for solubilization of the bovine zona pellucida in a hypotonic buffer containing 5% (v/v) beta-mercaptoethanol and 7 mol urea l-1 increased by 10% after fertilization. Coupling with a specific fluorescent thiol probe, monobromobimane (mBBr), was markedly greater in the zona pellucida of ovarian eggs compared with fertilized eggs, indicating that the cysteine residues in the zona pellucida of unfertilized eggs are oxidized to cystines during fertilization. After endo-beta-galactosidase digestion to remove N-acetyllactosamine repeats of the carbohydrate chains, three zona pellucida glycoproteins (ZPA, ZPB and ZPC) coupled with the fluorescent bimane groups were fractionated efficiently by reverse-phase HPLC. Estimation of bimane groups in the three components and SDS-PAGE revealed that intramolecular disulfide bonds in ZPA and intra- and intermolecular disulfide bonds in ZPB were formed during fertilization, but oxidation of cysteine residues in ZPC was low. Specific proteolysis of ZPA during fertilization was also observed. These results indicate that the formation of disulfide linkages together with specific proteolysis result in the construction of a rigid zona pellucida structure, which is responsible for hardening of the zona pellucida.

Animals↗

Malignant fibrous histiocytoma: a method to control intraoperative hemorrhage by clamping the feeding arteries.

Malignant fibrous histiocytoma (MFH), also referred to in the past as malignant fibrous xanthoma and fibroxanthosarcoma, is a tumor of mesenchymal tissue origin. A case of retroperitoneal MFH was reported. In this paper, we describe a method of hemostasis and intraoperative control of hemorrhage during resection of retroperitoneal MFH by snaring the feeding arteries. The patient was successfully operated on using this technique.

Arteries↗

[A case of simultaneous medullary hemorrhage and hematomyelia].

We reported a case of simultaneous medullary hemorrhage and hematomyelia. A 93-year-old woman, who had hypertension, was admitted to our hospital because of headache, numbness and weakness of the left extremities, and somnolence. On admission, weakness and disturbance of tactile sensations were observed in the left extremities. Magnetic resonance imaging showed medullary hemorrhage and hematomyelia and these two lesions were separated. Medullary hemorrhage was at the left dorsal paramedian area within mid-lower medulla oblongata, and hematomyelia was at the left side of the gray matter from medullo-cervical junction to upper cervical cord. Five days later from admission, weakness occurred in the right lower extremity and also in the upper extremity. This process suggested that the main lesion of tetraparesis was medullo-cervical junction. Review of 16 cases of medullary hemorrhage demonstrated that frequent neurological signs were palatal weakness, nystagmus, and disturbance of pain and temperature sense. But our case showed only disturbance of tactile sensations. Review of 19 cases of hematomyelia demonstrated that frequent neurological signs were sensory disturbance, paralysis and localized pain. Our case showed only paralysis. The cause of simultaneous hemorrhage was considered arteriovenous malformation or simultaneous multiple hypertensive hemorrhages.

Aged↗

The effect of the lipid A analog E5531 on phospholipid membrane properties.

In order to determine the effect of the lipid A analog, E5531, on phospholipid membranes, we used dipalmitoylphosphatidylcholine (DPPC) and investigated the physicochemical interaction between E5531 and DPPC membranes. E5531 and DPPC are miscible in the bulk phase at 25 degrees C. Within the E5531 mole fraction range (X(E5531)) of 0-0.5, E5531 decreased the zeta potentials of DPPC membranes but did not change the size of the DPPC liposomes. E5531/DPPC mixtures formed liposome-like structures. E5531 increased the fluidity of the DPPC membrane and decreased pyrene diffusion in the membrane. E5531 decreased the phase transition temperature and the cooperative interactions between DPPC molecules. These effects of E5531 on phospholipid membranes were different from those of lipid A from Escherichia coli and Salmonella minnesota.

1,2-Dipalmitoylphosphatidylcholine↗