Biomedical subjects
K Iijima
Publications and source records attributed to K Iijima.
Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men.
Endothelial dysfunction has been reported to be the initial step in atherosclerosis. A noninvasive technique that uses ultrasound to measure the intima-media thickness of the carotid artery has been applied to evaluate localized atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the brachial artery is related to the intima-media thickness of the carotid artery. Thirty-four men with atherosclerosis (mean+/-SE age 61+/-2 years) and 33 age-matched men without clinical atherosclerosis were examined. The intima-media thickness and plaque formation of the common carotid artery were assessed by B-mode ultrasonography. We also noninvasively measured brachial artery diameter by the same ultrasound machine when the subjects were at rest, during reactive hyperemia, which causes endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The atherosclerosis group had a significantly greater intima-media thickness of the common carotid artery than did the control group (1. 02+/-0.04 versus 0.91+/-0.03 mm, P<0.05). The flow-mediated diameter (FMD) increase (percent FMD=DeltaD/D x 100) in the atherosclerosis group was significantly smaller than that in the control group (2. 8+/-0.4% versus 5.1+/-0.6%, P<0.01). A significant negative correlation between the intima-media thickness of the carotid artery and percent FMD was found in all of the subjects. On multiple regression analysis, percent FMD showed a significant negative correlation with the intima-media thickness of the common carotid artery. These findings support the concept that endothelial dysfunction is significantly related to atherogenesis.
[Changes of activities of daily living and quality of life in a special nursing home during a one-year period].
The aim of this study was to examine the changes of activities of daily living and with quality of life of patients in a special nursing home founded in 1997 in Tsuwano Town, Shimane. We studied 19 special nursing home patients (age 69 to 96 years, mean age 83.3 years) for one year. To evaluate activities of daily living, mental decline, and quality of life, the Tokyo Metropolitan Institute of Gerontology Competence Index. Hasegawa's dementia rating scale, self-rating depression scale (Zung), apathy scale (Starkstein et al) and PGC morale scale (Lawton, subjective well-being scale) were used. The total score of the index of activities of daily living, self-rating depression scale, and the apathy score did not significantly change during one year. Although the total score of Hasegawa's dementia rating scale decreased significantly, PGC morale scale significantly improved during one year. These findings demonstrate that daily active rehabilitation had a beneficial effect on PGC morale scale in a special nursing home.
Effects of acupuncture on peripheral T lymphocyte subpopulation and amounts of cerebral catecholamines in mice.
The aim of this study was to investigate the effects of acupuncture on peripheral lymphocyte subpopulations and cerebral catecholamines. In order to examine the effects of acupuncture, two experiments were performed. Experiment 1: Eighteen female mice (strain; C57BL/6) at the age of 7 weeks were divided three groups, (a) sham operated (control; n=6), (b) ovariectomized (OVX; n=6), and (c) ovariectomized and stimulated by subcutaneous needles on acupuncture point, Shenshu (BL23) at the both sides of the back for 20 days (OVX+Acu; n=6). These animals were sacrificed at 20 days after needle insertion, and the splenic lymphoid cells were examined by two-color flow cytometry, using monoclonal antibodies (mAb) to the cell surface antigens, CD3, CD4, CD8a and NK1.1 (CD56). In the ovariectomized (OVX) group, the peripheral CD4/CD8 ratio was significantly increased and the ratio of natural killer (NK) cells (CD3-NK1.1+; CD3 negative, NK1.1 positive) to T lymphocytes was decreased compared to the sham control group. In the ovariectomized with needle insertion (OVX+Acu) group, the CD4/CD8 ratio was reduced, but the NK cells ratio was not changed compared to the OVX group. Experiment 2: To investigate the acute effects of subcutaneous needle insertion, male C57BL/6 mice (7 weeks old) were used (n=6, each group). The acupuncture points Shen-shu (BL23) on the backs of the male mice were also stimulated by subcutaneous needles for 3 and 7 days. As a result, the CD4/CD8 ratio was significantly decreased at day 3 and day 7, compared to the control group. On the other hand the NK cells ratio and activated T-cells were increased at day 7. The mitogenic activities in the splenic lymphocytes were also increased by acupuncture stimulation at day 3. Catecholamine contents in the hippocampus were measured by high performance liquid chromatography with the electro-chemical detector (ECD-HPLC) method. No significant change was observed in either dopamine contents or norepinephrine; however, dopamine metabolite, homovanillic acid (HVA) and DOPAC (3,4-dihydroxyphenylacetic acid) were increased at day 3. The study suggests that acupuncture has effects on peripheral lymphocyte subpopulations and may modulate mitogenic activity. In addition, acupuncture may stimulate dopamine turnover.
Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice.
The effects of acupuncture on the disorders elicited by abnormalities of endocrine system were investigated in ovariectomized mice. Female mice (strain; C57BL/6) were ovariectomized (OVX) and acupuncture points, Shenshu ([Japanese pictograph see text] : BL23) on both side of the back were continuously stimulated by subcutaneous needles for 20 days. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for catecholamine contents by high performance liquid chromatography with electro chemical detector (ECD-HPLC). The mitogenic activities of splenic lymphocytes were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTS) assay and alkaline phosphatase (ALP) assay. Furthermore, the effects of needle stimulation on learning and memory ability were studied by the step-through type passive avoidance test. Norepinephrine and dopamine contents in the frontoparietal cerebral cortex, ventral hippocampus and olfactory bulb were decreased in the OVX group, and both MTS activity and ALP activity were decreased 20 days after ovariectomy. The mean latent period was also shortened in the passive avoidance test in the OVX group. However, applying needle stimulation increased norepinephrine and dopamine contents in the brain regions, and enhanced mitogenic activities of splenic lymphocytes. The stimulation also improved memory-related behavior. It was concluded from this study that after mice were stimulated by subcutaneous needle insertion, overall changes were observed in central nervous system (including retention of memory) and immune functions. The study suggests that acupuncture improves the memory loss and decrease of immune responses accompanying aging and/or menopause, and the that it may have an important role in medical care for the elderly.
[Postoperative respiratory failure resulting from perioperative withdrawal of antiparkinsonian medications].
A patient with Parkinson's disease developed postoperative respiratory arrest due to perioperative withdrawal of antiparkinsonian medications and later presented a rapid recovery after parenteral administration of levodopa. In perioperative management of parkinsonian patients, it is important to continue antiparkinsonian medications until the operation is started and to administer levodopa parenteraly after the operation until oral administration of antiparkinsonian drugs becomes possible. In addition, we must pay attention to the choice of drugs so that parkinsonism may not be induced or aggravated.
[Recurrence rate of H. pylori after successful eradication and second eradication therapy after initial failure of treatment].
Three hundred thirty-three patient (116 gastric ulcer, 119 duodenal ulcer, 98 gastritis) who were successfully eradicated were enrolled in the study of H. pylori recurrence rate. H. pylori status was determined by histology, rapid urease test, 13C-urea breath test. The mean of the follow-up period was 13.3 months (2-56 months), and 15 patients showed negative to positive conversion of H. pylori. The recurrence rate was 4.4% for one year and 8.3% for two years using Kaplan-Meier analysis. Second eradication therapy after initial failure is another concern. Nineteen patients were assigned to receive an 1-week new triple therapy (clarithromycin, metronidazole and PPI), in whom a 2-week course of dual therapy (amoxicillin plus PPI) failed (group1). Another 15 patients in whom the 1-week new triple therapy failed were switched to the 2-week course of dual therapy plus ecabet sodium (group2). H. pylori was eradicated in 84.2% (16/19) of patients in group1 and 86.7% (13/15) in group2.
[Increased acid secretion after Helicobacter pylori eradication is the important risk factor of acute duodenitis and reflux esophagitis].
The aims of this study were to investigate whether the changes in gastric acid secretion after H. pylori eradication might influence the development of acute duodenitis (AD) and reflux esophagitis (RE). Stimulated acid output was assessed by EGT (mEq/10 min), which is the new endoscopic method of gastric secretory testing described previously. Changes in the EGT values before and after eradication were divided into 4 groups; decreased group, no change group, increased group, markedly increased group. Results estimated by EGT demonstrated that AD and RE development after eradication significantly correlated with the increase of acid secretion. In conclusion, the increase of acid secretion was thought to be one of the most important risk factors of both AD and RE developed after H. pylori eradication.
Molecular characterization of total kininogen deficiency in Japanese patients.
Kininogens are multifunctional plasma glycoproteins. There are two forms of human kininogen: low molecular weight kininogen (LK) and high molecular weight kininogen (HK). Both are derived from the same gene by alternative splicing. Some patients with kininogen deficiency have been reported to be deficient only in HK while others are deficient in both HK and LK (total kininogen deficiency). We analyzed three Japanese patients with total kininogen deficiency by the Csp45I digestion study of exon 5 as previously reported in Williams trait and found that two had the same point mutation of C to T at base 22 of exon 5, resulting in a transition of CGA (Arg) codon to TGA (Stop) codon. This is the first report of molecular characterization of total kininogen deficiency in the Japanese population.
Apico-aortic shunt: an alternate to the aorto-aortic shunt.
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[Effects on health status in students from attending a "juku"].
Between November and December 1993 a questionnaire survey concerning the lifestyle and health status was performed on 1.314 elementary school children living in Tokyo and its suburbs. In this study the following items were included: 1) sleeping habits, 2) physical activity, 3) playing habits, 4) eating habits, 5) attending a "juku", private cram school to prepare children for entrance examinations, 6) commuting hours, 7) 20 subjective symptoms regarding health, and so on. The results were as follows: 1. 61.9% of students were attending a "juku". 2. The number of hours of sleep, playing after school and watching TV decreased with the frequency of attending a "juku". The students who were attending "juku" more than 3 times a week had the shortest number of those hours, and the students who did not attend any "juku" had the longest of those hours. 3. To determine health status, 20 subjective symptoms were scored. The average number of subjective symptoms was 5.0. That of the students who were attending "juku" more than 3 times a week was 5.5. 4. Of the 20 subjective symptoms, 7 items were correlated to the frequency of attending "juku". To remove the effect of other factors, multiple logistic regression analysis was applied to determine correlation of 7 subjective items and other factors including attending "juku". As a result attending "juku" more than three times a week were associated with the two symptoms of "sleepy" and "eye fatigue".
[The production and coexistence of neurotransmitters in the neurons of the rat's locus coeruleus].
The production and coexistence of neurotransmitters in the locus coeruleus is reviewed. Immunocytochemical and in situ hybridization evidence demonstrated that the LC consists mainly of a single cell population that is producing GABA and 5-HT in addition to noradrenaline (NA) simultaneously in single neurons. The coexistence of GABA, 5-HT and NA in single LC neurons was proved by identifying the same neurons in adjacent sections alternately immunostained by different antisera. In situ hybridization detected the signals of glutamic acid decarboxylase mRNA and tryptophan hydroxylase mRNA indicating the presence of GABA/GAD system and the ability to produce 5-HT in many LC neurons. Neuroanatomical studies strongly suggest that a single NA cell population produces multiple transmitters so that the LC can play a role in mechanism controlling the human's adaptation to environmental changes. The present author introduces three different recent works concerning the LC. Caffé concluded that the concept of a NA-ergic cell population in all mammals is questionable. In similar cases to the domestic pig's LC, acetylcholinesterase activity, muscarinic and nicotinic receptor proteins should be checked. Tohyama et al. examined various receptor proteins in the LC and found localization of GAGAA, glutamate and glycine receptors. Maeda et al. reported that doaminergic neurons in the hypothalamus play a powerful role in mechanisms controlling the activity of NA-ergic neurons in the LC. Senile dementia of Alzheimer type causes marked atrophy and cell loss in the LC as well as the frontal lobe of the cerebrum. Molecular biology of the cell has been devoted to clarify the pathology of this fatal disease.
Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in rat aortic smooth muscle cells.
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of nuclear receptors, is expressed at a high level in adipose tissue and plays an important role in adipocyte differentiation. In the present study, we identified the expression of PPARgamma in rat aortic smooth muscle cells (RASMC) using reverse transcription-polymerase chain reaction and gel mobility shift assay. In addition, to investigate whether PPARgamma in RASMC is functional or not, we examined the effect of two specific ligands for PPARgamma, a thiazolidinedione anti-diabetic agent, troglitazone, and 15-deoxy-Delta12,14-prostaglandin J2, on the transcriptional activity of PPAR responsive element (PPRE). A significant increase in the activity of PPRE by addition of these ligands was found. These results suggest that in RASMC, target genes for PPARgamma may be activated by specific ligands for PPARgamma through PPRE in their promoters. In conclusion, PPARgamma is expressed and functional in vascular smooth muscle cells.
GPIIb/IIIa integrin antagonists with the new conformational restriction unit, trisubstituted beta-amino acid derivatives, and a substituted benzamidine structure.
Ethyl N-[3-(2-fluoro-4-(thiazolidin-3-yl(imino)methyl)benzoyl)amino-2, 2-dimethylpentanoyl]piperidine-4-acetate 40 (NSL-96184) is a highly potent and orally active fibrinogen receptor antagonist, which is characterized by the presence of the trisubstituted beta-amino acid residue, 3-ethyl-2,2-dimethyl-beta-alanine. This compound was developed on the basis of the SAR study of N-[3-(N-4-amidinobenzoyl)amino-2, 2-dimethyl-3-phenylpropionyl]piperidine-4-acetic acid 1(NSL-95301) with the derivatization focused on the central trisubstituted beta-amino acid unit as well as the basic amidinobenzoyl unit, and the esterification of the carboxyl group for prodrug composition. Compound 1, which was reported in our previous study, was discovered by the application of combinatorial chemistry. The molecular modeling study suggests that the trisubstituted beta-amino acid unit is responsible for fixing the molecule to its active conformation. Compound 40 showed an excellent profile in the in vitro and in vivo studies for its human platelet aggregation inhibitory activity and oral availability in guinea pigs. This oral availability largely depends on the modification of the amidino group with a cyclic secondary amine, i.e., thiazolidine in 40. In in vivo studies, the onset of the antiplatelet action of 40 is very fast after oral administration, whereas its duration of action is relatively short. These results suggest that 40 has an excellent therapeutic potential, especially for antithrombotic treatment in the acute phase. 3-Substituted-2,2-dimethyl-beta-amino acid residues would serve as new and useful linear templates to restrict the conformational flexibility of peptidomimetics.
cDNA isolation of Alzheimer's amyloid precursor protein from cholinergic nerve terminals of the electric organ of the electric ray.
Alzheimer's amyloid precursor protein (APP) is a transmembrane protein containing three phosphorylation sites in its cytoplasmic domain. In the present study, we isolated cDNA of APP from electric ray electric lobe (elAPP). This APP (elAPP699) consists of 699 amino acids, contains the beta-amyloid domain and has 80.7% similarity with the human APP695 isoform. The cytoplasmic domain, including three phosphorylation sites, was completely conserved. In the nerve terminals of the cholinergic neuron from the electric ray electric organ, we found elAPP699 existed exclusively in the mature form. We found the phosphorylated form of mature elAPP699 in the nerve terminal as well as in cell body. Immature elAPP699 was not subject to phosphorylation. Our findings indicate that, in neurons, the phosphorylation of APP occurs after maturation.
Halofuginone inhibits neointimal formation of cultured rat aorta in a concentration-dependent fashion in vitro.
Halofuginone, an anticoccidial quinoazolinone, can specifically inhibit collagen type alpha1 (I) synthesis and gene expression, and also inhibits cultured smooth muscle cell proliferation. The aim of this study was to investigate the effect of halofuginone on neointimal formation of rat aorta after culture in a concentration-dependent manner in vitro. Thoracic aorta of Wistar rats was removed and manipulated to damage the endothelium under sterile conditions, and culture for 15 days in halofuginone-free or halofuginone-added culture medium (n = 20). Segments of cultured aorta were studied by histologic and immunohistochemical methods. Proliferation of neointimal layers consisting of loose multilayer cellular structure was observed in the halofuginone-free control group after 15 days of rat aorta culture, and neointimal formation was significantly decreased as an increasing concentration of halofuginone was added. As with precultured fresh aorta, no intimal proliferation was observed in the cultured segments of aorta with 500 ng/ml halofuginone added to culture medium. The proliferation of cell nuclear antigen index was significantly higher in the halofuginone-free control group than that in the halofuginone-added groups. The present results suggest that halofuginone can inhibit neointimal formation of rat aorta after culture in a concentration-dependent fashion in vitro.
Multiple combined therapy for severe Henoch-Schönlein nephritis in children.
From 1980 through 1992, 14 children with Henoch-Schönlein nephritis (HSN) showing severe glomerular changes (grade IV or V) were given a multiple combined therapy with prednisolone, cyclophosphamide, heparin/warfarin, and dipyridamole, and were followed for 7.5+/-0.9 years. The period between the onset of nephritis and the start of therapy was 0.8+/-0.4 years. Ten patients underwent follow-up biopsy after therapy. The percentage of glomeruli having crescents/segmental lesions was significantly reduced after therapy (70%+/-5% vs. 42%+/-7%, P <0.01), due mainly to the resolution of crescents (51%+/-8% vs. 13%+/-5%, P <0.01). Thus, histological grade was significantly improved (5 grade IV and 5 grade V vs. 7 grade III and 3 grade IV, P <0.01). After an average follow-up period of 7.5 years, 9 patients showed normal urine and renal function, 4 showed minor urinary abnormalities, and 1 heavy proteinuria. No patient developed chronic renal insufficiency. These findings suggest that the multiple combined therapy could be effective. for histologically severe HSN, although a prospective controlled study should be performed.
Expression of type IV collagen in the developing human kidney.
The distribution of alpha1-6 chains of type IV collagen (alpha1-6(IV)) in human fetal kidneys was examined by indirect immunofluorescence. By 11 weeks of gestation, alpha1, 2, 3, 4, and 6(IV) were already present, but alpha5(IV) appeared relatively late, at 21 weeks. Alpha1(IV) and alpha2(IV) were present in all basement membranes, alpha3(IV) and alpha4(IV) were restricted to the glomerular basement membrane and parts of the tubular basement membrane. Alpha5(IV) was distributed in the glomerular basement membrane, Bowman's capsule, and parts of the tubular basement membrane. Alpha6(IV) was present in the Bowman's capsule, parts of the tubular basement membrane, and occurred in parts of the glomerular basement membrane at the early capillary loop stage, but disappeared during the later capillary loop stage.