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Biomedical subjects

T Imai

Publications and source records attributed to T Imai.

At least 469 records · Page 26Linked to original sources
PubMed1995

Stereoselective hydrolysis and penetration of propranolol prodrugs: in vitro evaluation using hairless mouse skin.

Stereoselective hydrolysis of two ester prodrugs of propranolol, isovaleryl propranolol (IV-PL) and cyclopropanoyl propranolol (CP-PL), was studied in Tris-HCl buffer (pH 7.4) containing 0.15 M KCl, skin and liver homogenates, 5% plasma in Tris-HCl buffer, skin cytosol and microsomes, and liver cytosol and microsomes. The hydrolysis rate constants of (R)-isomers of the prodrugs were 1.1-30.3 times greater than those of the respective (S)-isomers in tissue preparations. Skin showed considerable metabolic activity and very high stereoselectivity (R/S ratio: 7.3-30.3). The hydrolyzing capacities of buffer and different tissue preparations per milligram of protein content were in the following increasing order: buffer < skin homogenate < plasma < liver homogenate. The studies with microsomes and cytosol indicated that the esterases, which are responsible for the hydrolysis of prodrugs, were mainly present in the cytosolic and microsomal fractions of skin and liver, respectively. There was a good correlation between the octanol-buffer partition coefficients of propranolol and its prodrugs and the skin partition coefficient. In vitro stereoselective penetration of propranolol and the prodrugs through full-thickness hairless mouse skin was evaluated with flow-through diffusion cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Estimation of the degree of acclimatization to high altitude by a rapid and simple physiological examination.

The recent expansion in the geographical areas open to human activity has made it desirable to have an objective method to evaluate the degree of high-altitude acclimatization. In this study, we measured the arterial oxygen saturation value at rest and just after exercise in healthy high-altitude trekkers using a transportable pulse oximeter. During a 100-day stay at high altitude (around 4000 m), the degree of arterial hemoglobin saturation measured at rest was relatively stable. However, shortly after arrival at high altitude, even light exercise induced an acute reduction in the degree of arterial hemoglobin saturation; this reduction was ameliorated as the trekkers became acclimatized to the high altitude. Preliminary short trekking to high altitudes does not appear sufficient to induce this response. It is suggested that this rapid and simple physiological examination, the measurement of arterial oxygen saturation value after light exercise, could be a convenient means of estimating the level of high-altitude acclimatization among healthy subjects.

Acclimatization↗
PubMed1995

Topographic involvement of the striatal efferents in basal ganglia of patients with adult-onset motor neuron disease with basophilic inclusions.

This report concerns the topographic immunohistochemical analysis of the putamen, globus pallidus (GP) and substantia nigra (SN) of two patients with adult-onset motor neuron disease with basophilic inclusions (MND/BIs), seven patients with sporadic classic amyotrophic lateral sclerosis (sporadic ALS) and five neurologically normal individuals. The striatal efferent terminals of the GP and SN were visualized immunohistochemically using antibodies to met-enkephalin (MEnk) and substance P (SP). In specimens from patients with sporadic ALS and normal subjects there was intense immunostaining for MEnk and SP throughout the external and internal segments of the GP, respectively. By contrast, a marked reduction of MEnk- and SP-positive striatal efferents was seen in the ventrocaudal portions of both GP segments from the MND/BIs patients. Moreover, while MEnk-positive striosomes was readily detected in the putamen of normals and sporadic ALS patients, there was significant reduction in MEnk immunoreactivity, and no evidence of striosomal organization in the putamen of MND/BIs patients. In addition, whereas the SN of patients with sporadic ALS expressed SP, the ventrolateral SN portion of the MND/BIs patient tested had reduced immunoreactivity. The present findings on patients with MND/BIs may represent a reflection of the topographic striatum degeneration in this disease and appear to provide additional evidence for the heterogeneity of MND.

Adult↗
PubMed1995

Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low alpha-tocopherol diet.

Three series of experiments demonstrated that sesame seed and its lignans cause significant elevation of alpha-tocopherol content in rats. In Experiment 1, 20% sesame seed (with a negligible amount of alpha-tocopherol) supplementing 10 (low), 50 (normal), or 250 (high) mg/kg alpha-tocopherol diets (protein and fat concentrations in diets were adjusted to 200 and 110 g/kg, respectively) all caused a significant increase of alpha-tocopherol in the blood and tissue of rats. In Experiment 2, groups of rats were fed five different diets: a vitamin E-free control diet, a low alpha-tocopherol diet, and three low alpha-tocopherol diets supplemented with 5, 10, and 15% sesame seed. Changes in lipid peroxides in liver, red blood cell hemolysis, and pyruvate kinase activity, as indices of vitamin E deficiency, were examined. These indices were high in the low alpha-tocopherol diet, whereas supplementation with even 5% sesame seed suppressed these indices completely and caused a significant increase of alpha-tocopherol content in the plasma and liver. In Experiment 3, two diets containing sesame lignan (sesaminol or sesamin) and low alpha-tocopherol were tested. Results in both of the sesame lignan-fed groups were comparable to those observed in the sesame seed-fed groups as shown in Experiment 2. These experiments indicate that sesame seed lignans enhance vitamin E activity in rats fed a low alpha-tocopherol diet and cause a marked increase in alpha-tocopherol concentration in the blood and tissue of rats fed an alpha-tocopherol-containing diet with sesame seed or its lignans.

Animals↗
PubMed1995

Characterization of immunoreactive adrenomedullin in human plasma and urine.

Adrenomedullin(AM) is a novel vasodilator peptide recently isolated from pheochromocytoma. Using a specific and sensitive radioimmunoassay for human AM, we have characterized immunoreactive AM in human plasma and urine. Patients with chronic renal failure had about five-fold higher plasma immunoreactive AM levels than normal subjects, which did not change before and after hemodialysis. Immunoreactive AM was present in normal human urine, whose concentrations were about six-fold greater than those in human plasma. Reverse-phase HPLC of human plasma and urine revealed that immunoreactive AM emerged as a single peak at a position identical to that of authentic human AM(1-52). These data suggest that circulating AM is cleared by the kidney and urinary excretion of AM may be derived from glomerular filtration and/or its renal production.

Adrenomedullin↗
PubMed1995

Significance of epidermal growth factor receptor and c-erbB-2 protein expression in transitional cell cancer of the upper urinary tract for tumour recurrence at the urinary bladder.

An immunohistochemical study of the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 protein was performed in fresh-frozen sections from 30 patients with transitional cell cancers (TCCs) of the upper urinary tract (15 renal pelvic cancers, 15 ureteral cancers) who underwent total nephroureterectomy. We followed them and examined whether TCC appeared in the urinary bladder. The follow-up period ranged from 116 to 2348 days (mean 666 days). The mean period until a secondary urinary bladder cancer appeared was 306 days (116-829 days). Thirteen of those 30 TCCs (43.3%) showed increased expression of EGFR, and 11 TCCs (36.7%) showed increased expression of c-erbB-2. In 12 of 30 patients (40.0%), a secondary urinary bladder cancer appeared after surgery. In only one of the ten patients (10.0%) whose tumours did not exhibit increased expression of either of these receptors the tumour recurred in bladder. On the other hand, in 11 of 20 (55.0%) patients whose tumours had increased EGFR and/or c-erbB-2 expression, secondary urinary bladder cancers recurred after surgery (P < 0.05). Thus, the recurrence rate of TCCs with increased EGFR and/or c-erbB-2 expression was significantly higher than that of tumours showing no increased expression of these receptors (P < 0.01). These results suggest that the immunohistochemical detection of the expression of EGFR and c-erbB-2 in urothelial cancers of the upper urinary tract might be a useful method for determining the likelihood of secondary bladder cancer recurrences.

Aged↗
PubMed1995

Immortalisation of human oesophageal epithelial cells by a recombinant SV40 adenovirus vector.

We introduced the origin-defective SV40 early gene into cultured human oesophageal epithelial cells by infection of a recombinant SV40 adenovirus vector. The virus-infected cells formed colonies 3-4 weeks after infection in medium containing fetal calf serum. When the cells derived from 'serum-resistant' colonies were then maintained in the serum-free medium with a low calcium ion concentration, some of them passed the cell crisis and kept growing for over 12 months. These cells, regarded as immortalised cells, resembled the primarily cultured oesophageal epithelial cells in morphology and had some of their original characteristics. Treatment of the cells with a high calcium concentration induced phenotypic changes. These cells still responded to transforming growth factor beta. When the immortalised cells were injected into severe combined immunodeficient mice, they transiently formed epithelial cysts, although the typical differentiation pattern of the oesophageal epithelium was not observed. These cysts regressed within 2 months without development into tumours. The results indicated that human oesophageal epithelial cells were reproducibly immortalised by infection with a recombinant SV40 adenovirus vector at relatively high efficiency. The immortalised cells should be useful in studies on oesophageal carcinogenesis and in assessing the cooperative effects with other oncogene products or carcinogens.

Animals↗
PubMed1995

Endothelin synthesis and receptors in human endometrium throughout the normal menstrual cycle.

This study was undertaken to investigate the presence of messenger RNA (mRNA) for prepro-endothelin-I (ET-1) and the known receptor subtypes (ETA and ETB) in human endometrium at different stages of the menstrual cycle obtained at hysterectomy. Northern blot analysis revealed expression of ET-1 mRNA in human endometrium during the normal menstrual cycle. The concentration of ET-1 mRNA in endometrial tissue was greater during the menstrual and proliferative phases than during the ovulatory and secretory phases. Immunoreactive ET-1 was secreted into the medium of isolated endometrial stromal cells. Oestradiol and progesterone significantly attenuated ET-1 release in endometrial stromal cells cultured for 6 days. ETA and ETB mRNA were also present in endometrial tissue of the normal cycle. The concentration of ETA receptor mRNA was greater in the proliferative phase than in the secretory phase, whereas expression of ETB mRNA increased in menstrual phase. ET-1 significantly increased extracellular accumulation of cyclic AMP (cAMP), intracellular generation of inositol phosphates and significantly enhanced DNA synthesis in cultured endometrial stromal cells from the proliferative phase. Our results showed that human endometrial cells synthesized and released ET-1, and contained ETA and ETB receptors which were functionally coupled to phosphoinositide breakdown and to adenylate cyclase with the increase of cAMP by ET-1 stimulation. Our findings suggest that ET-1 may have a potential autocrine and/or paracrine function in human endometrial stromal cells.

Cells, Cultured↗
PubMed1995

Isolation and identification of adenosine triphosphoribosyl nicotinamide adenine dinucleotidephosphate from Azotobacter vinelandii.

A novel type of pyridine nucleotide, containing two adenosine triphosphate ribose residues rather than one, was isolated from Azotobacter vinelandii strain O. The nucleotide was shown to be 2"- or 3"-(2'-phosphoadenosine-5'-diphosphoribosyl)nicotinamide adenine dinucleotide phosphate, in which 2'-phospho-5'-diphosphoadenosylribose was glycosidically linked to the NADP at position 2' or 3' of the nicotinamide mononucleotide moiety. The ATPribosylNADP did not show coenzyme activity for yeast glucose 6-phosphate dehydrogenase, nor was it cleaved by Neurospora crassa NAD(P) glycohydrolase, indicating that the biological properties conferred on the beta-NADP molecule were largely modified by the attachment of the ATP-ribose group.

Adenosine Triphosphate↗
PubMed1995

Structures of cDNAs encoding the muscle-type and non-muscle-type isozymes of lamprey fructose bisphosphate aldolases and the evolution of aldolase genes.

Nearly full-length cDNA clones for muscle-type and non-muscle-type aldolase mRNAs were cloned from lambda gt10 cDNA libraries constructed from skeletal muscle and liver mRNAs of lamprey (Entosphenus japonicus). The cDNA-M8 has 2,240 bp carrying an open reading frame of 1,089 bp which encodes 362 amino acids without the amino terminal methionine, while the cDNA-L3 is 1,761 bp in length and has an open reading frame of 1,092 bp, which encodes 363 amino acids without the methionine. We designated the cDNA clones M8 and L3 as the muscle-type and non-muscle-type aldolase cDNAs, respectively. The entire amino acid sequences deduced from cDNA-M8 and -L3 show a high degree of identity to one another (76%) and also to vertebrate aldolases A (74-76%), B (68-70%), and C (71-76%) and Drosophila melanogaster aldolases alpha, beta, and gamma (66-67%). Northern blot analyses using the 3'-noncoding sequences of cDNA-M8 and -L3 as hybridization probes indicated that the muscle-type mRNA is expressed mainly in the skeletal muscle, heart muscle, brain, and some other tissues, but probably not in liver, while the non-muscle-type mRNA is expressed mainly in the liver and also in brain and other tissues, except for the heart muscle. Phylogenetic analyses showed that both muscle-type and non-muscle-type aldolases of lamprey resemble one another and might share a common ancestor with vertebrate aldolases A and C, but they are not direct ancestors of vertebrate aldolases.

Amino Acid Sequence↗
PubMed1995

Synthesis of pyridine nucleotide analogs using rabbit spleen pyridine nucleotide glycohydrolase and stereospecificity of the transglycosidation reaction.

Seven pyridine nucleotide analogs were synthesized, including nicotinic acid mononucleotide, nicotinic acid-adenine dinucleotide, and nicotinic acid-adenine dinucleotidephosphate, by means of the transglycosidase activity of rabbit spleen pyridine nucleotide glycohydrolase. The velocity ratio of the transglycosidation to the hydrolysis in the presence of 16 mM nicotinamide mononucleotide and 0.3 M nicotinic acid at pH 5.2 was greater than 10 and the transglycosidation/hydrolysis partition ratio was estimated to be (12 +/- 2) x 10(3). The partition ratio values obtained with 3-acetylpyridine and nicotinylglycine were smaller than that with nicotinic acid. Configurational analysis of pyridinium C-N glycosidic linkages of the transglycosidation products by means of 1H-NMR, UV, CD, and paper chromatography indicated that the configuration was completely retained and absolutely beta. Retention of the configuration, together with the substrate specificity of the enzyme for the beta-pyridinium linkage and formation of the intermediary enzyme-phosphoribosyl (or ADP-ribosyl) complex during the enzyme catalysis, indicated that the transglycosidation reaction catalyzed by the enzyme proceeds through the double replacement mechanism.

Animals↗
PubMed1995

Changes in epidermal growth factor receptor and the levels of its ligands during menstrual cycle in human endometrium.

We examined menstrual cycle-dependent changes in the expression of human endometrial epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and epidermal growth factor receptor (EGFR) and their mRNA using immunoblot analysis, 125I-EGF binding, and competitive reverse transcription and polymerase chain reaction (RT-PCR). We also studied their localization in the endometrial tissue by immunohistochemistry. Endometrial samples were obtained at three stages of menstruation: the early follicular stage, which exhibits low serum estradiol (E2) and progesterone (P) levels; the late follicular stage, which exhibits high E2 and low P levels; and the luteal stage, which exhibits high E2 and P levels. Immunohistochemical examination showed that EGF, TGF alpha, and EGFR were localized to the endometrial epithelium. Immunoblot analysis revealed that endometrial EGF, TGF alpha, and EGFR levels were significantly (p < 0.01) increased at the late follicular and luteal stages compared to the early follicular stage. 125I-EGF-specific binding levels at the late follicular and luteal stages were significantly (p < 0.01) higher than at the early follicular stage, consistent with the results of immunoblot analysis. Competitive RT-PCR revealed that EGF, TGF alpha, and EGFR mRNA levels were significantly (p < 0.01) higher at the late follicular and luteal stages than at the early follicular stage. Changes in EGF, TGF alpha, and EGFR mRNA levels were consistent with changes in protein levels. These findings suggest that synthesis and expression of human endometrial EGF, TGF alpha, and EGFR vary with the stage of the menstrual cycle and that their expression in the human endometrium is associated with the increase in the serum E2 but not with the increase in P levels.

Binding, Competitive↗
PubMed1995

Effect of calcium antagonist, nicardipine, on cerebral blood flow in postasphyxial newborn piglets.

An experiment was carried out in nine piglets within 24 h after birth (control group: four, nicardipine group: five) for the purpose of evaluating the effects of a calcium antagonist, nicardipine, on cerebral blood flow changes induced by asphyxia neonatorum. Under respiratory control with a mechanical ventilator, the animals were exposed to hypoxia. The inspiratory oxygen level was lowered at 15 min intervals from 0.08 to 0.06 and then to 0.05. When bradycardia (heart rate; 60/min or less) was observed, 100% oxygen, adrenaline, and sodium bicarbonate were administered for resuscitation. Nicardipine was administered at a dosage of 10 micrograms/kg via bolus injection 30 min after the resuscitation. It was administered thereafter at a rate of 10 micrograms/kg per h. The cerebral blood flow was measured using a laser Doppler velocimeter. The cerebral blood flow, electroencephalograph (EEG), blood pressure, and heart rate were continuously measured for 120 min after the resuscitation. In the control group, the mean arterial pressure 35 min after the resuscitation was 60 mmHg or more. However, the cerebral blood flow was lower than the prehypoxia value in the animals with a mean arterial pressure of 75 mmHg or less. In the nicardipine group, the mean arterial pressure was lower, but the cerebral blood flow was higher than the prehypoxia value and cerebral ischemia was not induced. The mean arterial pressure 120 min after the resuscitation was 72.0 +/- 8.2 mmHg in the control group, while it was 56.7 +/- 7.5 mmHg in the nicardipine group. It was significantly lower in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Partial clinical improvement in Upshaw-Schulman syndrome following prostacyclin infusion.

We report on a Japanese girl with Upshaw-Schulman syndrome, a congenital disorder characterized by recurrent thrombocytopenia, microangiopathic hemolytic anemia, proteinuria and hematuria that can be transiently improved by the transfusion of plasma or various plasma components. Unusually Large von Willebrand Factor (ULvWF) multimers were found during both relapse and remission phases. Serial plasma levels of 6-keto-prostaglandin F1 alpha (PGF1 alpha), the stable metabolite of prostacyclin (PGI2), were low at relapse. When the patient was treated with continuous PGI2 infusion, the microangiopathic hemolytic process gradually subsided within 10 days. These results suggest that PGI2 may be partly involved in the pathogenesis of this congenital disorder.

Anemia, Hemolytic, Congenital↗
PubMed1995

The relationship between viability and intracellular pH in the yeast Saccharomyces cerevisiae.

The relationship between viability (cell proliferation activity) and intracellular pH in the yeast Saccharomyces cerevisiae was investigated by using cells that had been deactivated by low-temperature storage, ethanol treatment, or heat treatment. The intracellular pH was measured with a microscopic image processor or a spectrofluorophotometer. At first, the intracellular pH measurements of individual cells were compared with slide culture results by microscopic image processing. A clear correlation existed between the proliferation activity and intracellular pH. Moreover, by spectrofluorophotometry analysis, it was found that there was a relationship between the viability and intracellular pH of brewing yeast under conditions of low external pH (n = 15, r = 0.960, P = 0.001). This relationship was also observed in baker's yeast (n = 13, r = 0.950, P = 0.001). On the other hand, when the fluorescein staining method was used in these experiments, the relationship between viability and staining percentage was not observed. From these results, intracellular pH was found to be a sensitive factor for estimating yeast physiology. The possible role of cell deterioration is also discussed.

Cell Division↗
PubMed1995

Intranasal instillation of diesel exhaust particulates and antigen in mice modulated cytokine productions in cervical lymph node cells.

To investigate cytokine production stimulated by diesel exhaust particulates (DEP) and antigen through the intranasal route, mice were administered with DEP mixed with ovalbumin (OA) 3 times at an interval of 3 weeks. After the last instillation, cervical lymph node cells (LNC) were cultured in vitro with OA and antigen-presenting cells. The proliferative response to OA in cervical LNC from mice instilled with DEP and OA was noted to have increased significantly compared to mice instilled with OA alone. Interleukin 4 (IL-4) and interferon (IFN)-gamma in culture supernatants were measured with ELISA. OA-stimulated IL-4 production in cervical LNC from mice instilled with DEP and OA markedly increased beyond that in the control mice. In contrast, OA-stimulated IFN-gamma production in cervical LNC from mice instilled with OA was 3 times that for DEP and OA-instilled mice. OA-specific IgE antibody in sera showed a trend to be increased in mice intranasally instilled with DEP and OA. These results suggest that intranasal instillation of DEP and antigen in mice may modulate in vitro antigen-stimulated cytokine production from cervical LNC with a consequent increase in IgE antibody production.

Administration, Intranasal↗
PubMed1995

Chemical compositions of 300 lower urinary tract calculi and associated disorders in the urinary tract.

The stones removed from 273 patients (220 males, 53 females) with bladder stones and 27 patients with urethral stones (males) were analyzed by infrared spectroscopy. Of these stones 50.0% contained magnesium ammonium phosphate (MAP), 39.9% calcium (oxalate and/or phosphate), 9.4% uric acid (urate), and 0.7% cystine. The disorders associated with bladder stones were prostatic hyperplasia and cancer (47.8%), neurogenic bladder (11.8%), urethral stricture (3.6%) and so on in males, and neurogenic bladder (48.1%), after operation of uterus (29.0%), bladder cancer (5.7%) and so on in females. Urinary infections were complications in 59.3% of patients with MAP stones, 41.2% with urate stones and 20.0% with calcium stones. The most often isolated bacteria from the infected urine were of the Proteus species.

Adolescent↗