Cimetidine and immunoreactivity.
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Cimetidine↗
Biomedical subjects
K Tsuchiya
Publications and source records attributed to K Tsuchiya.
Effect of the selective CCKB receptor antagonist LY288513 on conditioned fear stress in rats.
In order to investigate the involvement of cholecystokinin (CCK) in the regulation of anxiety, the effect of the selective non-peptide CCKB receptor antagonist LY288513 ((4S, 5R)-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-1-pyrazolidinecarboxamide+ ++) on freezing behavior induced by conditioned fear stress was examined using a time-sampling procedure. Rats were individually subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty-four hours after the footshock, the rats were again placed in the shock chamber and observed for 5 min without shocks: this procedure is termed conditioned fear stress. Subcutaneous administration of LY288513 30 min before footshock (0.3 mg/kg) and 30 min before conditioned fear stress (0.03 mg/kg) reduced conditioned freezing. This indicates that LY288513 blocked both the acquisition and expression of conditioned fear. The relatively selective non-peptide CCKA receptor antagonist, lorglumide (D, L-4-(3,4-dichlorobenzoylamino)-5-(diphentylamino)-5-oxo-pent anoic acid), blocked the expression of conditioned fear, though only at a high dose (1.0 mg/kg). The peripheral non-peptide CCKA/B receptor antagonist, loxiglumide (D, L-4-(3,4-dichlorobenzoylamino)-5- (N-3-methoxypropyl-pentylamino)-5-oxo-pentanoic acid), failed to do so. These results suggest that brain CCKB receptors are involved in the regulation of anxiety.
Animals↗
A new approach to analysis of human sweating.
In human skin transplanted to the back of 3 strains of immuno-deficient mice the function of the eccrine sweat glands of the human transplant was tested by topical intradermal application of pilocarpine, adrenaline and atropine + pilocarpine. Sweat responses were observed in pre-selected fields of observation by means of video macroscope. The iodine starch reaction served as an indicator for the appearance of sweat sport and permitted the evaluation of areas wetted by sweat in the field of observation. Among 9 animals tested, the hybrids between the CB-17-scid mouse and the BALB/cA-nu mouse (BALB/cA-nu,scid) seemed to exhibit the most consistent sweating response to local pharmacological stimulation. According to histological examination, eccrine sweat glands were preserved in human skin transplanted into the back skin of the BALB/cA-nu,scid mouse strain. The heterologous, human skin graft provides a novel model permitting, independent of the normal sweat gland innervation, the analysis of molecular receptors of sweat gland cells by which the actions of natural transmitters and pharmacological agents are transduced.
Animals↗
In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure.
This study tested the effects of hydrostatic pressure (10 MPa) on adult articular chondrocyte mRNA and extracellular matrix synthesis in vitro. High density primary cultures of bovine chondrocytes were exposed to hydrostatic pressure applied intermittently at 1 Hz or constantly for 4 hours in serum-free medium or in medium containing 1% fetal bovine serum. mRNAs for aggrecan, types I and II collagen, and beta-actin were analyzed by Northern blots and quantified by slot blots. Proteoglycan synthesis was quantified by 35SO4 uptake into cetylpyridinium chloride-precipitable glycosaminoglycans, and cell-associated aggrecan and type-II collagen were detected by immunohistochemical techniques. In serum-free medium, intermittent pressure increased aggrecan mRNA signal by 14% and constant pressure decreased type-II collagen mRNA signal by 16% (p < 0.05). In the presence of 1% fetal bovine serum, intermittent pressure increased aggrecan and type-II collagen mRNA signals by 31% (p < 0.01) and 36% (p < 0.001), respectively, whereas constant pressure had no effect on either mRNA. Intermittent and constant pressure stimulated glycosaminoglycan synthesis 65% (p < 0.001) and 32% (p < 0.05), respectively. Immunohistochemical detection of cell-associated aggrecan and type-II collagen was increased in response to both intermittent and constant pressure. These data support the hypothesis that physiologic hydrostatic pressure directly influences the extracellular matrix metabolism of articular chondrocytes.
Aggrecans↗
Endothelium-dependent relaxation of rat thoracic aorta by amrinone-induced nitric oxide release.
To determine whether amrinone and its induced increase of cyclic AMP releases nitric oxide and enhances endothelium-dependent vascular relaxation, we studied nitric oxide production and vascular relaxation of rat thoracic aorta on treatment with amrinone and forskolin, an activator of adenylate cyclase. When 20 microM amrinone was applied to ring segments of aorta previously contracted with phenylephrine, relaxation was greater in segments with endothelium than in those without (% relaxation 94 +/- 4 vs 37 +/- 7%, P < 0.01). However, a higher concentration of amrinone (> 50 microM) induced the same degree of relaxation in ring segments with or without endothelium, probably due to its direct effect on vascular smooth muscle. The maximal relaxant concentration (100 microM) of amrinone induced an increase (2.5 fold) in cyclic GMP in ring segments. Forskolin also induced concentration-dependent relaxation, but removal of the endothelium attenuated the relaxation induced by forskolin about seven-fold. NG-nitro L-arginine reversed the relaxation induced by amrinone or forskolin in ring segments with, but not without, endothelium. Nitric oxide production in ring segments of aorta, following application of amrinone or forskolin, was detected by nitric oxide-selective electrode and electron paramagnetic resonance spin trapping methods. Pre-treatment with NG-nitro L-arginine or removal of the endothelium suppressed nitric oxide production by amrinone or forskolin. These data showed that amrinone enhances the release of nitric oxide from rat aortic endothelial cells, and induces endothelium-derived relaxing factor/nitric oxide-mediated vasodilation.
Amrinone↗
Endotoxin-induced L-arginine pathway produces nitric oxide and modulates the Ca2+-activated K+ channel in cultured human dermal papilla cells.
Endotoxin includes an enzyme that synthesizes nitric oxide (NO) from l-arginine (NO synthase) in vascular smooth muscles cells, macrophages, and fibroblasts, leading to the release of NO. We evaluated the release of NO and its intracellular action on the Ca2+-activated K+ channel (KCa channel) in cultured human dermal papilla cells by use of the electron paramagnetic response (EPR) spin trapping method and the patch clamp technique. In dermal papilla cells pretreated for 24 h with endotoxin (1 microgram/microliter), application of 1 microM L-arginine generated NO, although no measurable release of NO was observed in cells without endotoxin pretreatment, as determined by the EPR spin trapping method. With the patch clamp technique, we found that the KCa channel of dermal papilla cells had high conductance and was voltage dependent. In addition, after endotoxin pretreatment, the extracellular application of 100 microM l-arginine modulated the KCa channel in the cell-attached patch configurations. In inside-out patch configuration, however, NO produced by L-arginine itself did not modulate the Kca channel. The modulation of the KCa channel was suppressed by pretreatment with 100 microM N omega-nitro-L arginine methyl ester, and inhibitor of inducible and constitutive NO synthases. Methylene blue, a blocker of guanylate cyclase, inhibited the L-arginine-induced activation of the Kca channel. Theses results indicate that the endotoxin-induced L-arginine pathway cell generates No, which consequently modulated the KCa channel in cultured human dermal papilla cells by increasing of cyclic GMP-dependent phosphorylation.
Arginine↗
Seroepidemiological survey of lymphocytic choriomeningitis virus in wild house mice in China with particular reference to their subspecies.
Serum samples from 337 wild house mice (Mus musculus) from 35 sites in China, collected in 1992 and 1993, were examined for antibodies against lymphocytic choriomeningitis virus (LCMV). Ten samples from eight sites were found to contain such antibodies. Six of the eight positive sites were located in the territory of M. m. gansuensis. One of the other two sites was located in the territory of M. m. castaneus in southern China and the other site was in a habitat of M. m. castaneus which had invaded into the western end of the territory of M. m. homourus. It seems likely that LCMV is distributed in the territories of M. m. gansuensis and M. m. castaneus in China. This is the first report of detection of these antibodies in wild house mice in China and specifically in the territories of M. m. gansuensis and M. m. castaneus.
Animals↗
Aldosterone-dependent regulation of Na-K-ATPase subunit mRNA in the rat CCD: competitive PCR analysis.
In the cortical collecting duct (CCD), aldosterone increases the number of functionally active Na-K-adenosin-etriphosphatase (Na-K-ATPase) molecules by a mechanism involving an isoform-specific increase in the abundance of the Na-K-ATPase alpha 1- and beta 1-subunit protein. However, the molecular basis for the response, particularly in the mammalian CCD in vivo, has remained unclear. To resolve this issue, reverse transcription (RT) and a competitive polymerase chain reaction (PCR) were employed to study mineralocorticoid-dependent regulation of alpha 1- and beta 1-subunit mRNA in the rat CCD. Na-K-ATPase subunit-specific oligonucleotides primers were used in the PCR to amplify reverse-transcribed subunit mRNA (RT-mRNA) from single microdissected CCD. Control templates were constructed (84-bp deletion mutation of the rat Na-K-ATPase alpha 1-subunit cDNA and 70-bp deletion of the beta 1-subunit cDNA), serially diluted, and coamplified with the wild-type Na-K-ATPase subunit RT-mRNA from single CCD. PCR products of predicted size were observed by ethidium bromide staining. Southern blots with an internal subunit-specific oligonucleotide confirmed Na-K-ATPase alpha 1- and beta 1-subunit identity. The ratio of the amplified wild-type to mutant PCR products was found to be linear over the range of input control cDNA tested so that the amount of subunit mRNA could be determined. A chronic reduction in corticosteroid levels by bilateral adrenalectomy (7 days) reduced the apparent level of alpha 1-subunit transcript by 54.0 +/- 6.3% but not the beta 1-subunit. Administering aldosterone to physiological levels is sufficient to restore CCD alpha 1-subunit mRNA abundance toward control levels within 6 h. We conclude the following: 1) regulation of Na-K-ATPase of CCD in vivo can be attributed, at least in part, to mineralocorticoid-dependent control of Na-K-ATPase alpha 1-subunit mRNA abundance; and 2) competitive PCR may provide a sensitive and quantitative tool for determining hormone-dependent regulation of mRNA abundance in nephron segments.
Adrenalectomy↗
Short communication: MR imaging of fetal brain abnormalities using a HASTE sequence.
HASTE (half-Fourier acquisition single-shot turbo spin echo) is a sequence that enables T2 weighted magnetic resonance (MR) images to be obtained in a few seconds. The purpose of this study was to evaluate the usefulness of this sequence in the diagnosis of fetal cerebral abnormalities. Five fetuses suspected of having cerebral abnormalities on ultrasound examination were studied by MR imaging using the HASTE sequence in utero. We compared the images with post-natal MR images or computed tomography (CT) scans. In four fetuses, the abnormality was diagnosed correctly, and the diagnosis was almost correct in the remaining fetus. This sequence is useful because it provides images of diagnostic quality in a very short scanning time.
Brain↗
Sound stimulation-induced vasomotor reflex in the central artery of the rabbit ear.
Effects of sound stimulation on the central artery of the rabbit ear were studied as a somato-autonomic reflex. Vasoconstriction and dilatation, caused by metronome sound stimulation, were estimated from the temperature fluctuations in the central artery of the ear, measured by a thermistor. To enhance the detection of temperature rises, moderately high background levels of arterial tone were established by exposing the tips of the ears to water at a temperature of 10 degrees C or 5 degrees C, prior to sound stimulation. A fall in arterial temperature due to vasoconstriction was observed immediately after the start of the 1-min sound stimulation, with a subsequent temperature rise which overshot the original basal level due to vasodilatation. A positive correlation between the ear temperature before sound stimulation and the temperature fall (p < 0.01), and a negative correlation between the ear temperature and the temperature rise (p < 0.05) were obtained. The temperature fall was blocked by phenoxybenzamine (9 mg/kg, i.p., p < 0.01). The subsequent rise was not influenced by atropine (3 mg/kg, i.p.) or phenoxybenzamine, however, it was attenuated by hexamethonium (6 mg/kg, i.p., p < 0.05). The temperature fall at the beginning of sound stimulation was related to alpha-adrenergic mechanism. The subsequent temperature rise was thought to be related to parasympathetic mechanism, excluding cholinergic mechanism.
Acoustic Stimulation↗
[One stage operation for ischemic heart disease and abdominal aortic aneurysm with ascending aortic calcification].
A 69-year-old man was referred to us with the diagnosis of abdominal aortic aneurysm (7 cm in diameter). Additionally his coronary arteriogram showed severe stenosis (LMT 75% and #6 99% delay). Because his ascending aorta was calcified severely, double CABG (LITA to LAD and RGEA to PL) was carried out in hypothermic ventricular fibrillation. Abdominal aortic aneurysm was replaced thereafter while the patient was still on cardiopulmonary bypass. His postoperative courses was satisfactory. In cases requiring early operation for both myocardial ischemia and abdominal aortic aneurysm, one stage operation was recommended. When atherosclerotic changes in the ascending aorta were severe, in situ arterial bypass grafting for ischemic heart disease under hypothermic ventricular fibrillation was useful.
Aged↗
[An unusual autopsy case of corticobasal degeneration--with special reference to clinicopathological differentiation from progressive supranuclear palsy and slowly progressive aphasia].
We report an unusual autopsy case of corticobasal degeneration. The patient was male who was 67 years old at the time of his death. He developed clumsiness of his right hand at age 65. Neurological examination at age 66 revealed supranuclear ophthalmoplegia of upward gaze and parkinsonism. Progressive supranuclear palsy was suspected. The patient's clinical course was rapidly progressive. Dementia developed nine months after the onset of the disease, and the patient manifested apallic syndrome at 21 months and died of pneumonia at about 25 months. At autopsy the brain weighed 1370g. Macroscopic examination revealed prominent atrophy of the anterior and parietal lobes, particularly of the pars opercularis in the left inferior frontal gyrus, and there was marked depigmentation of the substantia nigra. Histological examination showed neuronal loss, glial proliferation, spongy state, and ballooned neurons in the frontal and parietal lobes. Neuronal loss with glial proliferation was conspicuous in the striatum, pallidum, thalamus, and substantia nigra. There was slight neuronal loss in the dentate nucleus and locus ceruleus. Staining by Gallyas-Braak method revealed massive appearance of argyrophilic threads. This case is important in terms of the clinical differentiation from progressive supranuclear palsy, and is also interesting in regard to the pathological correlation with slowly progressive aphasia.
Aged↗
Three-dimensional helical CT angiography of skull base meningiomas.
PURPOSE: To describe the findings of skull base meningiomas on three-dimensional CT angiograms obtained with helical scanning and to evaluate the usefulness of this method. METHODS: Fifteen patients who had a meningioma near the skull base were examined with helical CT after receiving an intravenous bolus injection of contrast material. RESULTS: All meningiomas had either a honeycomb (12 patients) or solid (3 patients) pattern of enhancement. Bony structures of the skull base and adjacent major arteries that were displaced or surrounded by tumor were also evident. CONCLUSION: Three-dimensional CT angiography depicts the relationship between skull base meningiomas and neighboring bony and vascular structures clearly, quickly, and with minimal risk to the patient.
Adult↗
[Effects of topical application of isopropyl unoprostone on refraction and accommodation].
The effect of topical application of prostaglandin-related compound isopropyl unoprostone on refraction and accommodation were examined. Topical application of isopropyl unoprostone obviously reduced the intraocular pressure, but no significant change in refraction was observed. Amplitude of accommodation, i.e., near point and far point of accommodation, were kept unchanged, although isopropyl unoprostone produced a slight hyperopic shift in dark focus of accommodation. These findings suggest that the reduction of intraocular pressure needs to be explained by a mechanism other than the relaxation of ciliary muscles.
Accommodation, Ocular↗
Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid.
mac25, the subject of this report, was selected by the differential display of mRNA method in a search for genes overexpressed in senescent human mammary epithelial cells. mac25 had previously been cloned as a discrete gene, preferentially expressed in normal, leptomeningial cells compared with meningioma tumors. mac25 is another member of the insulin growth factor-binding protein (IGFBP) family. Insulin-like growth factors are potent mitogens for mammary epithelial cells, and the IGFBPs have been shown to modulate this mitogenic activity. We report here that mac25, unlike most IGFBPs, is down-regulated at the transcription level in mammary carcinoma cell lines, suggesting a tumor-suppressor role. The gene was mapped to chromosome 4q12. We found that mac25 accumulates in senescent cells and is up-regulated in normal, growing mammary epithelial cells by all-trans-retinoic acid or the synthetic retinoid fenretinide. These findings suggest that mac25 may be a downstream effector of retinoid chemoprevention in breast epithelial cells and that its tumor-suppressive role may involve a senescence pathway.
Amino Acid Sequence↗
Estimation of variation among individuals of biological half-time of cadmium calculated from accumulation data.
For heavy metals, many experimental studies using animals have revealed short biological half-times (BHTs) to be 1 year or less by administration of heavy metals. Tsuchiya and Sugita, however, devised an original method and first reported the possibility of a long BHT for cadmium (Cd) calculated from Cd accumulation in postmortem human organs and tissues by age using a nonlinear regression analysis employing a differential equation. According to their reports, the estimated values of Cd BHT were 12.1-22.7 years in the kidney. The estimated Cd BHTs are point estimators. The point estimator of Cd BHT has been used indiscriminately to derive safety levels for Cd in the air of work environments or foodstuffs in the general population without taking into consideration individual variation of Cd BHT. In the present study, the estimated variation among individuals of Cd BHT ranges from a few years to at least 100 years in the kidney. It is concluded that the estimated average BHT according to mathematical calculation should not be used indiscriminately to derive the safety level of cadmium exposure.
Adolescent↗
Goblet cell hyperplasia induced by Strongyloides venezuelensis-infection in Syrian golden hamster, Mesocricetus auratus.
The goblet cell response was examined in the jejunum of the Syrian golden hamster, Mesocricetus auratus, following infection with an intestinal helminth, Strongyloides venezuelensis. After subcutaneous inoculation with 3000 infective larvae (L3), the number of adult worms in the small intestine remained stable up to day 20 and then decreased. Before infection, the number of goblet cells in the jejunum was about 70/10 villi. The number of goblet cells slowly increased, though not significantly, until day 20 post-infection, and then rapidly increased with an inverse relationship to the worm burden. By day 43, when adult worms were almost completely expelled, the number of goblet cells was about 3-fold higher than that of control animals. Similar vigorous goblet cell hyperplasia has not been reported in Strongyloides spp. infection in other experimental animals. Histochemical study revealed that goblet cells in the jejunum of Syrian golden hamsters, unlike those of other experimental animals, produced and released highly sulfated mucins.
Animals↗
Hyperventilation alternating with apnea in neuroleptic malignant syndrome associated with metoclopramide and cisapride.
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Aged↗