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Biomedical subjects

Y Higashimoto

Publications and source records attributed to Y Higashimoto.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Diffuse aspiration bronchiolitis (DAB) produced in animals by repeated HCl microaspiration].

We recently reported that diffuse aspiration bronchiolitis (DAB) was detected in 1% of autopsied lungs of aged cases of pneumonia. We hypothesized whether repeated HCl micro-aspiration (RHMA) is involved in DAB and established an animal model by administering HCl intratracheally to rats every two days for 2 weeks. Saline was given to control animals in the same fashion. Then, we performed bronchio-alveolar lavage (BAL) or excised lungs for histologic examination. There was no difference in BAL cell counts, TNF alpha-production, elastase-like activity or albumin levels between the HCl and control groups. Histologically, DAB-like findings were observed in the HCl-treated animals. These data suggest that RHMA might be involved in DAB, while neither TNF alpha-production nor elastase-like activity may play a significant role in inducing DAB.

Animals↗
PubMed1994

[Influence of age on mouse pulmonary alveolar macrophage clonal growth].

Although monocyte influx has been suggested as the primary source of pulmonary alveolar macrophages (AM), increasing evidence from recent studies has indicated that AM may be sustained through a self-renewal mechanism. We evaluated the age-related changes of the clonal growth (colony formation) of AM in mice (C57BL/6N mice and senescence accelerated mice). The colony forming unit (CFU) of AM of 24 month old C57BL/6N mice was lower than that of AM of 4-month-old mice (p < 0.05). In SAMP6 (senescence accelerated mice), CFU of AM was decreased with aging (p < 0.05). In SAMR1 (controls for SAMP6), CFU of AM was decreased with aging (p < 0.001). In SAMR1, CFU of bone marrow (BM) adherent cells of 12-month-old mice was similar to that of 4-month-old mice. In SAMP6, CFU of BM adherent cells of 12-month-old mice was larger than that of 4-month-old mice (P < 0.005). It was concluded that the CFU of AM declined with aging, but the CFU of the BM adherent cells did not. The decline of the AM CFU may be partly responsible for the defect of the immune response of the alveolar space in the elderly.

Aging↗
PubMed1993

Effect of antrectomy and drug-induced achlorhydria on urinary excretion of N-terminal big gastrin immunoreactivity in rats.

Immunoreactivities of urinary N-terminal big gastrin and serum C-terminal gastrin were determined in intact and antrectomized rats by radioimmunoassay using two antisera specific for N- and C-termini of big gastrin, respectively. Gel filtration of urine extract from intact rat showed a single giant peak of N-terminal big gastrin immunoreactivity eluted in a later position than 1-17 gastrin-34, indicating that N-terminal peptides smaller than 1-17 gastrin-34 are excreted in urine. Serum C-terminal gastrin concentration in antrectomized rats was about one sixth that in intact rats. Urinary excretion of N-terminal big gastrin in antrectomized rats was about one sixth that in intact rats. 2 week treatment with E3810, a proton pump inhibitor, (40 mg/kg/day, s.c.) induced urinary excretion of N-terminal big gastrin in parallel with a marked increase in serum C-terminal gastrin concentration in intact rats. Antrectomy completely prevented both the increase in urinary excretion of N-terminal big gastrin and the elevation of serum C-terminal gastrin induced by administration of E3810. There was an excellent correlation between serum concentration of C-terminal gastrin and urinary excretion of N-terminal big gastrin. These results suggest that urinary N-terminal big gastrin, which mostly originates from the gastric antrum, is a useful indicator of gastrin secretion in the rat.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Isolation and characterization of the gene encoding rat glucose-dependent insulinotropic peptide.

The rat glucose-dependent insulinotropic peptide (GIP) gene has been isolated and characterized. The gene spans approximately 8.2 kilobase pairs (kb) and the GIP mRNA (0.8 kb) is encoded by six exons. The 42 amino acid hormone is encoded by exons 3 and 4. The exon-intron organization of the rat GIP gene revealed that the splice acceptor site for intron 2 is 24 nucleotides downstream compared to the comparable splice acceptor site in the human gene. This intron sliding results in an 8 amino acid deletion in the amino terminal extension of the prepropeptide. Primer extension analysis and RNase protection assay demonstrated the existence of multiple closely spaced sites for transcriptional initiation. Both the 5'-flanking region and intron 1 contain TATA and CCAAT boxes consistent with initiation of gene transcription, although a TATA box in intron 1 is functionally inactive in adult rats in spite of its reasonable location.

Amino Acid Sequence↗
PubMed1993

The effects of aging on the function of alveolar macrophages in mice.

In order to determine whether the function of alveolar macrophages (AM) is modulated by aging, we measured the TNF-alpha production, phagocytic function, and surface antigen expression of AM from young and old mice. When AM were primed by IFN-gamma (500 units/ml) and triggered by LPS (100 micrograms/ml), TNF-alpha production by AM was significantly smaller in old mice as compared with young mice (young mice: 161.7 +/- 28.2 units/ml; old mice: 89.3 +/- 13.6 units/ml, P < 0.05). The percentage of AM which phagocytosed latex particles (more than one particle) in old mice was significantly lower than in young mice (young: 78.1 +/- 2.5%; old: 62.8 +/- 3.4%, P < 0.05). Ia antigen expression of the AM was significantly higher and asialo-GM1 antigen expression was significantly lower in old mice than in young mice (Ia: young, 0.030 +/- 0.005; old, 0.092 +/- 0.024, P < 0.05; asialo-GM1: young, 0.-9 +/- 0.01; old, 0.75 +/- 0.07, P < 0.01). These results suggest that alveolar macrophage function is at least decreased in part with aging in mice.

Aging↗
PubMed1993

[An aspiration pneumonia in acute airway damage model induced by HCl and/or LPS].

The purpose of this study is to evaluate chemical and pathological changes of the lung and to elucidate the role of TNF alpha and elastase in acute lung injury induced by HCl or lipopolysaccharide (LPS). Anesthetized rats were injected with pH 1.4 0.7 ml/kg body weight of HCl and 0.5 mg/kg body weight (BW) of LPS (E. coli) into the lung. Acute tracheal injury model (Mendelson Syndrome) were made. Control animals received only saline. Animals were sacrificed 1, 6, or 12 hours after the HCl or LPS or HCl and LPS injection, bronchoalveolar-lavage (BAL) was performed in the same way in control and experimental groups. The other animals which were treated as well were excised by histology. There was neither increase in TNF alpha-production nor increase in neutrophils resulting from HCl injection only. Elastase-like activity was not detected in animals treated only with HCl. However, 1 hour after LPS injection, the production of TNF alpha (37.0 +/- 8.0 Units/ml) was significantly greater than that of the control group (12.1 +/- 4.2 Units/ml) in BALF. Six hours after HCl and LPS injection, the concentration of elastase-like activity (0.023 +/- 0.002 nM) was significantly greater than that of the LPS group (0.011 +/- 0.001 nM). Only patches of intraalveolar hemorrhage and elevation of fibrin was observed in the HCl injected rats at 1 hour after injection. Six hours after LPS injection, the alveolar spaces were filled with large amounts of neutrophils. These findings suggest that TNF alpha and elastase play a significant role in HCl and LPS-induced acute lung injury.

Acute Disease↗
PubMed1993

[Effects of aerosol oxitropium bromide and fenoterol on maximal exercise capacity in chronic obstructive pulmonary disease and their correlation with air flow during exercise and with parameters of maximal exercise].

To examine the effects of bronchodilators on maximal exercise capacity and their correlation with airflow during exercise in patients with chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized comparison between inhaled fenoterol (beta 2-agonist) and oxitropium bromide (anticholinergic agent) in 8 patients with stable COPD (mean age 73 years, mean FEV1 1.1 L, mean FEV1% 50%). Only oxitropium bromide resulted in statistically significant improvement in FEV1 40 min after inhalation. On maximal exercise, fenoterol did not affect oxygen uptake (VO2 max), minute ventilation (VEmax), respiratory frequency (Rfmax), ventilatory efficacy (VEmax/VO2 max), peak expiratory flow during exercise (PEFmax), heart rate (HRmax) and dyspnea (Borg Scale Slope). After oxitropium bromide, dyspnea during exercise and HRmax decreased significantly, but PEFmax and other parameters did not change significantly compared with control. There was no correlation between changes in dyspnea during exercise and changes in FEV1 and PEFmax after oxitropium bromide inhalation. We conclude that inhaled oxitropium bromide, an anticholinergic agent, reduces dyspnea during exercise in patients with COPD. This favorable effect was not due to change of airflow limitation during exercise, and other factors can thus influence reduction of dyspnea during exercise in these patients.

Administration, Inhalation↗
PubMed1992

Molecular cloning of rat glucose-dependent insulinotropic peptide (GIP).

A cDNA clone encoding glucose-dependent insulinotropic peptide (GIP) was identified that consisted of 34 bp of 5' untranslated sequence, an open reading frame of 432 bp and 115 bp in the 3' untranslated region. The deduced amino acid sequence revealed a 144 amino acid preprohormone consisting of a 43 amino acid N-terminal extension including a signal peptide, a 42 amino acid hormone, and a 59 amino acid C-terminal extension. Rat GIP differs from the human hormone by two amino acid substitutions: arginine for histidine at position 18 and leucine for isoleucine at position 40. A single mRNA from small intestine of approximately 800 bases was identified on Northern blot analysis in equivalent amounts in proximal and distal small intestine.

Amino Acid Sequence↗
PubMed1992

Inhibition of mouse alveolar macrophage production of tumor necrosis factor alpha by acute in vivo and in vitro exposure to tobacco smoke.

We investigated the effects of tobacco smoke exposure on the production of tumor necrosis factor alpha (TNF alpha) by alveolar macrophages (AM) in mice (C57BL/6). The results obtained are as follows: (1) In vivo tobacco smoke exposure caused a significant decrease in the production of TNF alpha by AM with the stimulation of lipopolysaccharide (LPS; control group: 19.32 +/- 5.52 U/ml, smoked group: 4.28 +/- 0.98 U/ml; p less than 0.05). (2) In vitro exposure of AM to tobacco smoke extracts (water-soluble extracts) also caused a decrease in the production of TNF alpha up to 93% of control with stimulation of LPS (p less than 0.05) without any decrease in cellular viability. We concluded that the production of TNF alpha by AM was impaired by smoking via direct action of the factors present in tobacco smoke.

Animals↗
PubMed1992

[Efficacy of magnetic resonance imaging in treatment of neuroblastoma].

Magnetic resonance imaging (MRI) was performed in 36 children with neuroblastoma at Chiba University from 1984 through 1989, and 29 patients of them were discussed about efficacy of MRI in treatment of neuroblastoma in this paper and the results were as follows. 1) MRI was difficult to differentiate tumor from normal kidney in the image intensity and was more efficient in determining the relationship of tumor to liver and to vascular structures. 2) MRI was better than CT in detecting the size and extent of tumor mass and in identifying lymph node spread using multiple planes. 3) MRI was more efficient than CT in defining displacement and encasement of renal vessels by tumor. It was useful to predict to reserve kidney before surgery. 4) MRI was useful to monitor tumor response to combined modalities of therapy. A favorable response was seen as a change in the image intensity in bone marrow metastases of neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed1991

[A case of primary intrapulmonary benign schwannoma].

A case of primary intrapulmonary schwannoma was described. A 72-year-old man was admitted to our hospital because of dry cough. A chest radiograph showed partial atelectasis of the middle lobe, but computed tomogram of the chest revealed no tumor shadow. Bronchoscopy disclosed a pale-yellow uneven endobronchial wall of the right middle lobe bronchus. Transbronchial biopsy revealed benign schwannoma. Primary intrapulmonary schwannoma has been rarely reported.

Aged↗
PubMed1990

Purification of N-terminal hexapeptide of big gastrin from human urine.

We previously demonstrated that extremely high amounts of N-terminal big gastrin (G-34) fragments are excreted in human urine and three of them are N-terminal octa-, nona-, and decapeptide of G-34. Our subsequent examination revealed that there exists a considerable amount of another N-terminal G-34 fragment in urine, less hydrophobic than the three peptides. We purified this fragment from urine of an achlorhydric patient and determined the structure: less than Glu-Leu-Gly-Pro-Gln-Gly. The purification was carried out by Sep-Pak C18 cartridges, Sephadex G-25, and reverse phase HPLC. The structure was determined by a combination of amino acid analysis, amino acid sequence analysis, and mass spectral analysis. N-terminal hexapeptide of G-34 is the second richest component of urinary N-terminal G-34 fragments next to N-terminal octapeptide of G-34 in normal subjects.

Achlorhydria↗
PubMed1990

NH2-terminal big gastrin immunoreactivity in human urine.

The concentrations and molecular forms of urinary and plasma gastrin from normal subjects were studied by radioimmunoassays using two region-specific antisera. Urinary concentration of NH2-terminal big gastrin (G-34) immunoreactivity was several hundred times as great as that of COOH-terminal gastrin immunoreactivity. Fractionation of urine extract showed a broad giant peak of NH2-terminal G-34 immunoreactivity (gastrin fragments "U") eluting in a later position than G-34(1-17) by Sephadex G-50 column chromatography. HPLC revealed that urinary NH2-terminal G-34 immunoreactivity was composed of four fragments including G-34(1-8), G-34(1-9), and G-34(1-10). Sephadex G-50 column chromatography of plasma extract revealed two or three peaks of NH2-terminal G-34 immunoreactivity, and a major peak eluted in the same position as urinary gastrin fragments "U". These results and data on renal clearances suggest that most of all gastrin fragments "U" in plasma are excreted in urine without renal reabsorption, whereas almost all of plasma COOH-terminal gastrin peptides including G-34 and little gastrin (G-17) are removed and metabolized in the kidney.

Adult↗
PubMed1990

Temporal profiles of urinary excretion of NH2-terminal big gastrin immunoreactivity in humans.

We studied the temporal profile of urinary NH2-terminal big gastrin immunoreactivity (NT G-34-IR) excretion in order to evaluate the dynamics of gastrin secretion. The temporal profile of urinary NT G-34-IR excretion in normal subjects represented three peaks corresponding to each meal. In contrast, the profile in antrectomized patients and patients under total parenteral nutrition (TPN) represented a flat pattern. Urinary NT G-34-IR excretions during fasting 2-h periods in antrectomized patients and TPN patients were about one-sixth and one-third, respectively, of basal NT G-34-IR excretion in normal subjects (53.1 +/- 13.9 pmol/h). Total urinary NT G-34-IR excretion during 24 h both in antrectomized patients (220 +/- 35 pmol/24 h) and TPN patients (390 +/- 68 pmol/24 h) was also significantly lower than in normal subjects (1985 +/- 403 pmol/24 h). The present study showed that the main source of urinary NT G-34-IR is the gastric antrum, that the main factor fluctuating its excretion is food intake, and that long-term TPN reduces basal gastrin secretion. Urinary NT G-34-IR would be a useful indicator for total gastrin secretion.

Adult↗
PubMed1990

[Usefulness of demand oxygen delivery system for patients with chronic respiratory failure due to mainly tuberculosis sequelae].

To evaluate the usefulness of a new oxymatic conserver, Demand Oxygen Delivery System (DODS), we compared DODS breathing with Standard steady flow (SF) breathing in thirteen subjects with chronic respiratory failure due to mainly tuberculosis sequelae. The value of the DODS (Oxymatic) is that it delivers oxygen only during early inspiration, so as to minimize loss from delivery during expiratory phase. Improvement of SaO2, measured by BIOX 3740, and PaO2 were observed at rest and on exercise. The oxygen consumption ratio of the DODS to the SF method was between 0.5 and 0.3, favoring the DODS over the SF method. In some patients DODS hardly ran at rest. But no problems are observed during exercise. The results indicate the effectiveness of DODS in advancement of quality of life patients with chronic respiratory failure.

Aged↗
PubMed1990

A possible indicator of urinary NH2-terminal big gastrin immunoreactivity for gastrin secretion.

Urinary and plasma gastrin immunoreactivities in normal subjects were studied by radioimmunoassays using three region-specific antisera. Urinary excretion of NH2-terminal big gastrin immunoreactivity (NT G-34-IR) in the fasting state (0.79 +/- 0.17 pmol/kg/h, mean +/- SE) was several hundred times as much as that of either COOH-terminal gastrin or gastrin/cholecystokinin immunoreactivity. Urinary NT G-34-IR increased significantly after feeding, and correlated closely with integrated plasma NT G-34-IR. Renal clearance of NT G-34-IR was 62.4 +/- 7.9 ml/min and about one hundred times greater than that of any other gastrin immunoreactivities, indicating that there exist different catabolic pathways of gastrin peptides in the kidney. Gel filtration of urine extract revealed that a single giant peak of NT G-34-IR eluted in a later position than NH2-terminal heptadecapeptide of big gastrin. These results suggest that most of plasma NT G-34-IR is excreted in urine, and urinary excretion of NT G-34-IR reflects well-integrated plasma NT G-34-IR. Therefore, urinary NT G-34-IR may serve as a feasible indicator for gastrin secretion.

Adult↗
PubMed1989

Purification and structural determination of urinary NH2-terminal big gastrin fragments.

We previously demonstrated that there existed extremely abundant NH2-terminal big gastrin immunoreactivity (NT G-34-IR) in human urine. This report describes the purification and sequence of NT G-34-IR from the urine of an achlorhydric patient. The purification was carried out by a combination of Sep-Pak C18 cartridges, Sephadex G-25, and HPLC steps using a radioimmunoassay specific for NH2-terminus of G-34 and ultraviolet absorption at 214 nm as monitors. Three peptides were isolated. The amino acid analysis, mass spectrometry, and sequence analysis confirmed the structures of urinary NT G-34 fragments being less than Glu-Leu-Gly-Pro-Gln-Gly-Pro-Pro, less than Glu-Leu-Gly-Pro-Gln-Gly- Pro-Pro-His, and less than Glu- Leu-Gly-Pro-Gln-Gly-Pro-Pro-His-Leu. NH2-terminal octapeptide of G-34 was the main component of urinary NT G-34-IR.

Achlorhydria↗