Contribution of GTP-binding protein to the actions of endothelin-1 on rabbit parasympathetic neurons.
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Afferent Pathways↗
Biomedical subjects
T Nishimura
Publications and source records attributed to T Nishimura.
[Affected siblings with Alzheimer's disease had missense mutation of codon 717 in amyloid precursor protein gene].
Using reverse genetic techniques, the gene responsible for familial Alzheimer's disease (FAD) is one of the clues to identify the pathogenesis of Alzheimer's disease (AD). Recently a missense mutation in the APP (amyloid precursor protein) gene (generally this mutation was called APP717) was detected in 2 Caucasian AD families and the same mutation was found in 3 Japanese AD families. We experienced brother's cases who were diagnosed as AD. Both of them and one normal person of the next generation had APP717. The first symptom of the elder brother (case 1) was forgetfulness at 52 years old, then dementia was advanced. In his clinical course there were characteristic findings such as the mirror sign, pseudodialog and jargon which has been rarely described in the Japanese literature. Finally he died of pneumonia at 57 years old. He was diagnosed as AD pathologically and physical findings of brain CT, SPECT (single photon emission computed tomography) and EEG supported this diagnosis clinically. The first symptom of the younger brother (case 2) was also forgetfulness at 45 years old, then severe dementia was advanced, at last he died of pneumonia at age 53 old. On the other hand the mother of the brothers died of severe dementia, so it was suspected that brothers died of severe dementia, so it was suspected that she had had AD. The clinical courses and pathological findings were thought to be typical of AD, namely there were no significant differences in comparison with other cases of FAD and sporadic AD.(ABSTRACT TRUNCATED AT 250 WORDS)
Alzheimer Disease↗
[Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation and the mutated genes for the prion protein].
Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Immunohistochemical study of the human olfactory system].
Taurine (2-aminoethane sulfonic acid) and carnosine (beta-alanyl-L-histidine) are found in large quantities in the olfactory epithelium and bulb. Taurine is a structurally simple amino acid, and has been reported to have several putative roles, such as neurotransmitter, neuromodulator, neurogrowth factor and to function in membrane stabilization. Carnosine, on the other hand, has been suggested as a putative neurotransmitter in the olfactory system. We have succeeded in visualizing taurine- and carnosine-like immunoreactivities (LI) in the human olfactory mucosa, and also carnosine-LI in the human olfactory bulb. For this investigation, we collected specimens of the human olfactory bulb by autopsy and from the olfactory mucosa by biopsy, and compared localization of taurine- and carnosine-LI in several cases. By means of biopsy using Nakano's forceps, samples of olfactory mucosa were obtained from 5 cases: a 17 year old female, 23 year old male, 46 year old male, 47 year old male, and a 57 year old male. The olfactory bulb of a 1 month old male was collected at autopsy. These specimens were processed for immunohistochemical study according to the peroxidase-antiperoxidase (PAP) method. In the olfactory epithelium, taurine-LI was demonstrated in some primary olfactory neurons, and in basal cells. Carnosine-LI was observed only in primary olfactory neurons, i.e., dendrites, vesicles and axonal bundles of olfactory receptor cells, but not in basal cells. In the olfactory bulb, the olfactory nerve layer and the glomerular layer showed carnosine-LI positive reactions. Therefore, taurine and carnosine may possibly coexist in some olfactory neurons. Olfactory receptor cells are classified as sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Studies on condensed-heterocyclic azolium cephalosporins. III. Synthesis and antibacterial activity of 7 beta-[2-(2-amino-5-substituted-thiazol-4-yl)-2 (Z)-alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl-3-cephem-4- carboxylates.
As a part of our research on the synthesis of cephalosporins bearing condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus, we describe herein the synthesis of 7 beta-[2-(2-amino-5-halogeno-, methylthio-, methylsulfinyl-, methylsulfonyl- and sulfothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporins and their antibacterial activity. Among the compounds prepared, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido]-3-(imidazo[1,5-a]-pyridinium-1-yl)methyl-3-cephem -4-carboxylate (14) showed good antibacterial activity against both Staphylococcus aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, whereas the antibacterial activity against other Gram-negative bacteria was a slightly lower than that of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(im ida zo [1,2-a]pyridinium (I-1) and imidazo[1,5-a]pyridinium (I-4)-1-yl)methyl-3-cephem-4-carboxylates.
Anti-Bacterial Agents↗
Studies on condensed-heterocyclic azolium cephalosporins. IV. Synthesis and antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins including SCE-2787.
The synthesis and in vitro antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetami do] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3- (condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-b]-pyridazinium-1-yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7 beta-[2-(5- amino-1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3-(imidaz o[1,2- b]pyridazinium-1-yl)methyl-3- cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation.
Cephalosporins↗
Studies on condensed-heterocyclic azolium cephalosporins. V. Synthesis and antibacterial activity of 3-(condensed-triazolo-pyridinium, -pyrimidinium, and -pyridazinium)-methyl cephalosporins.
As a part of our studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)2(Z)-methoxyiminoacetamido] cephalosporins (1-16, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido] cephalosporins (17,18) and 7 beta-[2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus. These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(5- methyl[1,2,3]triazolo-[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(6- methoxy[1,2,4]triazolo[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity.
Cephalosporins↗
[Laser photocoagulation of experimentally produced choroidal neovascularization. 2. Comparison of effects by dye and argon blue-green lasers].
Choroidal neovascularization was produced in 18 eyes of 12 rhesus monkeys by application of intense krypton laser photocoagulation. Eight weeks or later, a total of 34 choroidal neovascularizations were treated either by dye laser at wavelengths of 577 or 630 nm or by argon blue-green laser. The treated lesions were evaluated clinically and histopathologically from 24 hours to 3 months after treatment. All the treated lesions were apparently healed by each of the 3 laser modalities. Histopathologically, all the treated choroidal neovascularizations were occluded 24 hours after treatment. At 2 weeks to 3 months after treatment, newly-formed choroidal vessels were present in 3 of 9 lesions (33%) after 577 nm dye laser treatment, in 8 of 9 lesions (89%) after 630 nm dye laser treatment, and in 5 of 8 lesions (62%) after argon blue-green laser. These results seemed to show the clinical superiority of 577 nm dye laser in treating choroidal neovascularization.
Animals↗
Intraarterial lymphocyte-injection therapy for lymphedema of the leg: an examination using indium-111 oxine labeled autologous lymphocytes.
A 58-year-old female patient with lymphedema of the left leg was treated by repeated intraarterial lymphocyte-injection therapy. To elucidate whether the injected lymphocytes act at the affected site of the leg, we examined the distribution of the In-111 oxine labeled lymphocytes injected into the proximal artery to the affected leg in comparison with the distribution in the other, healthy, leg. The radioactivity of the affected leg was almost two times higher than that of the healthy leg during the first 30 min after injection, and it remained higher even after 24 hours. The circumference of the affected leg of the patient decreased steadily during her hospital stay. These results, together with the clinical findings, suggest that some of the intraarterially-injected lymphocytes remained in the affected leg at least 24 hours and might play some role in reducing the volume of lymphedematous fluid.
Blood Component Transfusion↗
[A case of hepatoma patient who showed an abnormally high level of serum IRI with the beads method].
A fifty four years old hepatoma patient admitted to the hospital for a surgical operation. Preoperative laboratory examination demonstrated that his serum IRI level was very high (423 microU/ml) when measured with a beads method, however RIA or a microplate method demonstrated normal values. We studied the mechanism of the discrepancy of IRI values. 1) Both the beads and microplate methods demonstrated the same IRI values when the patient's serum insulin was roughly purified with Sep-Pak. The beads method showed high IRI values in serum which passed through Sep-Pak, therefore contained no insulin. 2) The similar results were observed when the patient's serum fractionated by a gel-chromatography (Biogel P-30). The beads method demonstrated high IRI values in both insulin fractions and the fractions containing serum proteins bigger than 40,000 molecular weight. The microplate method demonstrated only one large peak of insulin. 3) When non-specific IgG of guinea pig was used as a fixed antibody instead of human insulin antibody of guinea pig that was used in the beads method, the patient's serum showed the similar values as that obtained with the beads method. We thereby concluded that the abnormal level of IRI by the beads method was derived from the unknown substance reacting with IgG of guinea pig in the patient's serum. After the surgical resection of hepatoma, the levels of IRI measured by the beads method decreased significantly, suggesting that the substance is related to hepatoma cells.
Animals↗
[Pulmonary uptake of thallium-201 in patients with congenital heart disease: comparison between total anomalous pulmonary venous connection and tetralogy of Fallot].
To evaluate the pulmonary extravascular space in patients with congenital heart disease, lung uptake of thallium-201 (T1-201) was quantitatively studied. A total of 50 T1-201 imagings were performed in 33 patients with total anomalous pulmonary venous connection (TAPVC); 4 preoperatively, 22 postoperatively in the early stage (within 6 months), and 24 in the late stage (7 months or later). The images consisted of 17 supracardiac TAPVC (type-I), 13 paracardiac (type-II) and 3 infracardiac (type-III). In patients with tetralogy of Fallot (T/F), T1-201 imaging was performed 15 times preoperatively, 12 in the early stage and 15 in the late stage, postoperatively. Furthermore, 29 patients with ventricular septal defect (VSD) or patent ductus arteriosus (PDA) were also studied preoperatively, and 21 in the late postoperative stage. Twenty-five patients with arrhythmias or a history of Kawasaki disease without perfusion defects were studied on T1-201 myocardial imaging. Lung uptake of T1-201 was analyzed with a computer using the anterior image of the chest, and the average count ratio of the right lung (P) to the left ventricular wall (LV) was calculated. P/LV values were compared between the patients before and after surgery, and differences in anatomical types in TAPVC were also evaluated. In TAPVC, P/LV values decreased gradually in the postoperative state, but were significantly higher than those of controls even in the late stage. In the late postoperative stage, type-I TAPVC had significantly higher P/LV values than those of type-II.(ABSTRACT TRUNCATED AT 250 WORDS)
Heart Defects, Congenital↗
[Epidemiological study of Alzheimer's disease, Pick's disease and subcortical dementia in Japan].
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Aged↗
[Slow virus infection: the Japanese clinical statistical data].
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Adolescent↗
[Laser photocoagulation for experimental choroidal neovascularization. 1. Mild dye laser photocoagulation].
The author treated experimentally produced choroidal neovascularization (ChNV) with mild dye laser photocoagulation (PHC). We treated these ChNVs with 590 nm wavelength, 200 microns spot size, 0.2 second duration and 50 mW of power. Eleven eyes of nine rhesus monkeys were used. Then these ChNVs were examined clinically and histopathologically at 24 hours, 2 weeks and a month after therapeutic PHC. Small ChNVs, less than 1/3 disc diameter healed successfully and histopathologically most of them were coagulated and disappeared. A few poorly developed ChNVs remained, but were well enveloped by the proliferating retinal pigment epithelial (RPE) cells. On the other hand, ChNVs of more than 1/3 disc diameter did not respond to weak PHC, grew actively over a month, and were not completely surrounded by proliferating RPE cells. These results suggest that by mild PHC, small ChNVs may be treatable, however, in large ChNVs, mild PHC may rather accelerate their activity.
Animals↗
[Dipyridamole-thallium myocardial imaging in patients unable to exercise adequately: comparison with arm and bicycle ergometer].
We assessed the usefulness of dipyridamole-thallium myocardial imaging in patients unable to exercise adequately, compared with arm-ergometer and standard (bicycle) ergometer. Fifty-six patients with arteriosclerosis obliterans, aortic aneurysm, aortic dissection and so on, who were revealed normal imaging, were studied. Only one of 13 cases with arm-ergometer and two of 14 with bicycle ergometer reached target heart rate. Lung thallium uptake in the cases with arm-ergometer (37 +/- 9%) is higher than that with dipyridamole (29 +/- 5%). This elevation may be confused with pectoralis muscle uptake. Washout rate is 45 +/- 9% with dipyridamole and 46 +/- 12% with bicycle ergometer, respectively, though there was no significant differences. Myocardial/background counts ratio with dipyridamole (4.6 +/- 0.8%) is significantly higher than that with arm and bicycle ergometer (arm-ergometer; 3.5 +/- 0.7, bicycle ergometer; 4.2 +/- 0.9). Then, myocardial image with dipyridamole have superior quality. We concluded that dipyridamole-thallium myocardial imaging is very useful in the patients who have suboptimal exercise efforts.
Aged↗
[Influence of hypertensive left ventricular hypertrophy on detection of ischemic area with exercise thallium-201 myocardial scintigraphy].
Sixty-four patients with single left anterior descending artery disease having effort angina (group A: 40 patients without hypertension, group B: 10 patients with hypertrophic hypertension, group C: 14 patients with non-hypertrophic hypertension) were assessed the influence of hypertensive left ventricular (LV) hypertrophy on detection of ischemic area. The criterion of hypertrophy by two-dimensional echocardiography was > 12 mm in the wall thickness of interventricular septal or posterior wall. Population in Group B might show low detectability in ischemic area by 201Tl myocardial scintigraphy (positive thallium rate 60%, defect score 2.7 +/- 3.6), and high lung thallium uptake and high frequence of ECG positive among three groups. In semiquantitative analysis, the washout rate of the posterolateral wall and %RD (delayed %uptake-initial %uptake) of the septal wall in patients with Group B were lowest among three groups. However, the washout rate in the septal wall against the posterior wall, and the initial %uptake and the delayed %uptake of the septal wall were not significantly different among three groups. We could conclude that the decreased washout rate in nonischemic area with hypertensive LV hypertrophy might make the ischemic area masked.
Aged↗
[Metabolite of 15-p-iodophenyl-3(R,S)-pentadecanoic acid (123I) in blood and urine].
We analyzed metabolites of 123I-BMIPP in blood and urine using rats, rabbits and human, while human samples were obtained from normal volunteers of Phase I clinical study. We estimated metabolic pathway of 123I-BMIPP as a myocardial metabolic imaging agent. Radioactivity accumulated in heart after administration gradually decreased and was mainly excreted to bladder via kidneys. The main radioactive component in blood was 123I-PIPA for any species and the urinary components were metabolic conjugates of 123I-PIPA. As results of these studies, we considered that 123I-BMIPP was metabolized to 123I-PIPA by alpha-oxidation process for the first step, follow by beta-oxidation process, then 123I-PIPA was released to blood from tissues. Moreover, 123I-PIPA in blood was conjugated with other compounds and excreted to the bladder.
Animals↗
[Laboratory and clinical studies of cefprozil in pediatric field].
Laboratory and clinical studies were done on cefprozil (CFPZ, BMY-28100). The results are summarized as follows. CFPZ was administered through the oral route to 2 children at a single dose of 7.5 mg/kg. After administration, peak serum levels of CFPZ obtained in the 2 cases were 6.71 micrograms/ml at 1 hour and 6.45 micrograms/ml at 2 hours, respectively and half-lives were 1.28 hours and 0.92 hour, respectively. The urinary excretion rates of CFPZ were 58.9% and 59.4%, respectively. Treatment with CFPZ was made in 37 cases of pediatric bacterial infections: 1 case of pharyngitis, 16 cases of tonsillitis, 16 cases of scarlet fever, 3 cases of impetigo, 1 case of UTI. Results obtained were excellent in 24 cases, good in 13 cases. No significant side effects due to the drug were observed, except 1 case of loose stool, 3 cases of eosinophilia, and 1 case each of elevated GOT and GPT.
Bacteria↗