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Biomedical subjects

M Ichikawa

Publications and source records attributed to M Ichikawa.

At least 181 records · Page 10Linked to original sources

Application of long-term cultured neurons in aging and neurological research: aluminum neurotoxicity, synaptic degeneration and Alzheimer's disease.

Dissociated hippocampal and cerebral cortical neurons from rat embryonic brain form many synapses in culture. The neuronal networks in culture fire spontaneously in synchronous oscillation and can be maintained for long periods of up to 6 months. To establish the relevance of this long-term culture to aging and neurodegenerative diseases, effects of long-term exposure to aluminum, a risk factor for Alzheimer's disease, on the cultured cortical neurons were investigated. It appeared that aluminium promoted the aggregation of amyloid beta-protein and enhanced its neurotoxicity.

Aluminum↗

Differential modulation of baroreceptor sensitivity by long-term antihypertensive treatment.

We investigated the effects of long-term oral treatment with four different classes of antihypertensive drugs (a thiazide diuretic [trichlormethiazide, 10 mg/kg per day]; a beta-blocker [atenolol, 90 mg/kg per day]; a calcium channel antagonist [nicardipine, 150 mg/kg per day]; and an angiotensin-converting enzyme inhibitor [enalapril maleate, 10 mg/kg per day]) on aortic baroreceptor activity in spontaneously hypertensive rats with chronic hypertension (36 weeks of age). Treatment with each of the four drugs, given from 10 to 36 weeks of age, similarly decreased arterial pressure (171 +/- 2 to 144 +/- 1 mm Hg, P < .01) and similarly decreased the threshold pressure for baroreceptors (116 +/- 3 to 103 +/- 1 mm Hg, P < .05). The four antihypertensive drugs also potentiated the maximal gain of the pressure-activity relation in these rats (untreated, 1.08 +/- 0.05% maximum/mm Hg); however, nicardipine and enalapril (1.77 +/- 0.04% and 1.70 +/- 0.06% maximum/mm Hg, respectively) augmented the maximal gain to a greater extent (P < .05 to .01) than did trichlormethiazide or atenolol (1.49 +/- 0.05% and 1.42 +/- 0.02% maximum/mm Hg, respectively). When the initiation of treatment was delayed to 28 weeks of age, no differences were found in the effects on either threshold pressure (104 +/- 1 mm Hg) or maximal gain (1.36 +/- 0.03% maximum/mm Hg) for all four drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Mass screening and age-specific incidence of neuroblastoma in Saitama Prefecture, Japan.

PURPOSE: To provide the population-based incidence rate of neuroblastoma and to determine the effect of mass screening on the annual age-specific incidence of the tumor in Saitama Prefecture, Japan, from 1981 to 1992. METHODS: Data on screened infants and patients detected by the screening were obtained from the records of the Prefectural Screening Center. Data on neuroblastomas in this area were obtained from the Children's Cancer Registry of the Saitama Prefectural Government (Prefectural Registry) and from the Japan Children's Cancer Registry (National Registry). Population data were obtained from the Prefectural Census. Mass screening for 6-month-old infants was performed by qualitative assessment of urinary vanillylmandelic acid (VMA) from June 1981 to September 1989 and by quantitative measurement of VMA/creatinine (Cre) and homovanillic acid (HVA)/Cre from October 1989 to December 1992. RESULTS: Between 1981 and 1992, 199 cases of neuroblastoma, which include 74 cases detected by mass screening, were identified in Saitama Prefecture. The incidence rate for children under 15 years of age increased from 6.4/10(6) to 20.1/10(6), that for children 0 to 4 years of age increased from 17.0/10(6) to 64.1/10(6), and that for infants under 1 year of age increased from 27.9/10(6) to 260.4/10(6) during these 12 years. No significant reduction in the incidence rate was observed for children over 1 year of age. CONCLUSION: The incidence rate for children under 15 years of age increased with mass screening. The rate for infants was sharply increased, with no corresponding decrease in the rate for children at older ages. These data suggest that there is a subset of neuroblastoma that can be detected by mass screening at 6 months of age but would not be diagnosed later clinically.

Adolescent↗

Histological evidence for neuroprotective action of nebracetam on ischemic neuronal injury in the hippocampus of stroke-prone spontaneously hypertensive rats.

The protective effect of nebracetam on ischemic neuronal damage was histologically examined in the pyramidal cell layer of the hippocampal CA1 subfield 7 days after operation using stroke-prone spontaneously hypertensive rats (SHRSP) subjected to 10-min bilateral carotid occlusion. Nebracetam (50 and 100 mg/kg), given orally 10 min after reperfusion, dose-dependently protected against ischemic delayed neuronal damage in the SHRSP with occlusion; however, the blood pressure remained unchanged following nebracetam administration. These findings further support the notion that nebracetam protects against ischemic delayed neuronal cell death in the hippocampus.

Animals↗

Effects of a fixed point on postural readjustments caused by a moving visual scene.

This study examined how postural readjustments caused by a moving scene can be affected by placing a fixed point (FP) onto the moving scene. Thirty-two healthy subjects participated in this study. Each subject maintained Romberg's position on a platform while vertical optokinetic stimulation (VOKS) was presented. A random dot pattern moving in a downward direction was projected on a large hemispherical screen placed in front of the subject. The magnitude of vection and forward displacement from the center of foot pressure (CFP) caused by VOKS were compared under two conditions: with and without FP. With FP, the magnitude of vection increased towards slow VOKS velocity, while forward displacement of CFP decreased significantly. These results indicate that an FP placed in a moving pattern may contribute to stabilizing postural orientations.

Adolescent↗

Report of a case of benign cystic mesothelioma.

A 32-yr-old man was admitted to Anjo Kosei Hospital for the examination of a cystic peritoneal lesion. This patient had a past medical history significant for an appendectomy. Ultrasonography and computed tomography revealed multiple cysts in the abdominal and pelvic cavities. An exploratory laparotomy was performed on July 1, 1993, revealing numerous thin-walled and translucent cysts in the serosal tissues of the parietal and visceral abdominal peritoneum. These cysts were excised surgically because of clinical suspicion of pseudo-myxoma peritonei. Microscopic examination revealed cysts within the thin cyst wall that were composed of fibrous connective tissue and lined by a single layer of cuboidal or flattened epithelium. Immunohistochemical and ultrastructural studies demonstrated that the lining cells were of mesothelial origin, and the diagnosis was benign cystic mesothelioma. In this paper, we present appropriate diagnostic and treatment procedures for benign cystic mesothelioma and discuss the particular usefulness of using immunohistochemical methods to achieve a histological diagnosis.

Adult↗

Vicia villosa agglutinin inhibits the fasciculation of vomeronasal axons in fetal rat vomeronasal organ culture.

The vomeronasal organ of rat was cultured from embryonic 15-day littermates. During 4-8 days in vitro, vomeronasal axons originating from the explants of vomeronasal organ formed 2-3 large fascicles. When Vicia villosa agglutinin (VVA) was added to the culture medium, fasciculation of the vomeronasal axons was inhibited. The timing of addition and the duration of the presence of VVA were related to the inhibition of fasciculation of vomeronasal axons. Glycocojugates that bind with the VVA may therefore play an important role in the fasciculation of developing vomeronasal axons.

Animals↗

Signal transmission in the parallel fiber-Purkinje cell system visualized by high-resolution imaging.

We investigated the synaptic transmission in the parallel fiber-Purkinje cell system at high spatio-temporal resolution by using voltage-sensitive dyes and an imaging system. In rat cerebellar slices, cut in the frontal plane or in a plane of the cerebellar surface, local electrical stimulation induced volleys of action potentials in the parallel fibers; subsequent postsynaptic responses from Purkinje cells were observed along the volleys' entire trajectories. Furthermore, the formation of an ordered spatial gradient in parallel fiber conduction velocity across the depth of the molecular layer during postnatal development was observed. In preparations of adult, but not of immature rats, the conduction velocity of parallel fibers in the deep molecular layer was faster than in its more superficial regions. Our observations demonstrate that parallel fibers can mediate Purkinje cell excitation effectively and over considerable distances in a well-organized spatio-temporal manner, thus supporting the classical view of the physiological role assigned to the parallel fibers.

Action Potentials↗

Role of nitric oxide in regulation of baroreceptor reflex.

The possible role of nitric oxide (NO) on modulating sympathetic nerve activity through its action on baroreceptor reflex arc was investigated. L-Arginine, a precursor of NO, and NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, were separately infused intravenously in increasing doses in 126 pentobarbital-anesthetized rabbits. Mean arterial pressure (MAP), heart rate (HR), aortic nerve activity (ANA), cervical (CSNA) and renal sympathetic nerve activities (RSNA) were recorded. L-Arginine infusion decreased MAP (P < 0.05), ANA (P < 0.05), CSNA (P < 0.05) and RSNA (P < 0.05) without changes in HR. Infusion of D-arginine, an enantiomer of L-arginine, and simultaneous infusion of L-arginine and L-NMMA, did not elicit such changes. L-NMMA infusion increased MAP (P < 0.05) and ANA (P < 0.05) and decreased HR (P < 0.05), while it tended to increase CSNA and RSNA without significance. Infusion of L-arginine or L-NMMA did not alter the slope of ANA, CSNA, RSNA, or HR in relation to MAP. These results suggest that NO modulates efferent sympathetic nerve activity, not by altering the afferent or efferent limbs of the baroreceptor reflex arc, but by interacting with the sympathetic pathway in the central nervous system.

Afferent Pathways↗

A multiple assay for vitamin D metabolites without high-performance liquid chromatography.

We describe a multiple assay of the three main vitamin D metabolites, 25OHD, 24,25(OH)2D, and 1,25(OH)2D, in 0.5 ml of serum, which does not require high-performance liquid chromatography. The assay involves extracting the serum with acetonitrile, separation and purification on a C-18/OH cartridge and a Sep-Pak silica cartridge, and quantitation using 1,25(OH)2D receptors from calf mammary gland for 1,25(OH)2D, and vitamin D binding protein for 25OHD and 24,25(OH)2D. For 25OHD, 24,25(OH)2D, and 1,25(OH)2D, the method is sensitive to 0.125 ng/tube, 0.025 ng/tube, and 0.5 pg/tube, with the B50 occurring at 1 ng/tube, 0.2 ng/tube, and 8 pg/tube, respectively. The coefficients of variation (SD/mean x 100%) intraassay (n = 8) were 5.4, 12.8, and 6.6% and interassay (n = 6) 12.3, 10.8, and 8.6%. The overall recovery was 80.4 +/- 5.5, 58.0 +/- 6.3, and 77.4 +/- 5.6% (mean +/- SD, n = 40). The validity of the assay was confirmed by dilution test, analytical recovery of added vitamin D metabolites, and comparison with a standard assay using HPLC. This assay offers a simple, rapid, and precise method with which to determine the three main vitamin D metabolites in small serum samples, so it should be particularly useful in studies of pediatrics or small animals.

Acetonitriles↗

Monoclonal antibody (VOM2) specific for the luminal surface of the rat vomeronasal sensory epithelium.

Monoclonal antibodies were raised and selected for reactivity with the luminal surface of the rat vomeronasal organ. Among the monoclonal antibodies generated, the one named VOM2 showed specific immunoreactivity within the luminal surface of the rat vomeronasal sensory epithelium. The VOM2 antigen appeared weakly on the luminal surface at postnatal day 14 (P14). After P21, VOM2 immunoreactivity as strong as that in the adult vomeronasal organ was observed. Immunofluorescence staining using VOM2 antibody showed no reactivity on the luminal surface of the adult mouse or hamster vomeronasal organ. An immunoblotting analysis showed that the VOM2 antigen was a protein with a molecular weight of 24,500.

Animals↗

Differential development of binding sites of two lectins in the vomeronasal axons of the rat accessory olfactory bulb.

Binding of fluorochrome-conjugated lectins, Bandeiraea simplicifolia lectin-I (BSL-I) and Vicia villosa agglutinin (VVA), to the vomeronasal axons was investigated in the accessory olfactory bulb (AOB) of developing rats at embryonic day (E) 16, 18, and 20, and postnatal day (P) 0, 3, 7, 14, and 28. Intense fluorescence for VVA was first observed at E18, and the position-specific binding pattern observed in adults was established at P0; intense fluorescence for VVA was observed in the posterior 2/3 of the vomeronasal nerve layer (VNL) and glomerular layer (GL) and weak fluorescence was present in the anterior 1/3 of these layers. Fluorescence for BSL-I was observed in the posterior half of VNL and GL at P0; the area bound with BSL-I was expanded to the anterior area and intensity of the fluorescence increased as the development proceeded. At P28, binding of BSL-I was observed in the entire VNL and GL as identical to adults. These results indicate that the binding sites of BSL-I and VVA in the vomeronasal axons at the level of rat AOB develop differentially during ontogeny, suggesting that rat VN axons consist of two subpopulations expressing different glycoconjugates.

Animals↗

Social environment affects synaptic structure in the glomerulus of the accessory olfactory bulb of the hamster.

The accessory olfactory bulb (AOB) is the primary center of the vomeronasal chemosensory system. The effects of differential rearing on the numerical density and size of synapse as well as neuronal size were examined in the AOB of adult hamster. At 30 days from birth, male littermates were assigned to one of three experimental conditions. (1) the IC (isolated condition), where a male animal was housed alone, (2) the NC (neighbor condition), where one male was separated from two females by wire shields, and (3) the SC (social condition), where two males and two females were housed together. After 2 months of differential rearing, the AOBs of male littermates from each experimental set were prepared for morphological examination. The lengths of synaptic contact zones and the density of synapses in the glomeruli of the AOB as well as the area of somata of mitral/tufted cells were measured with an image analyzer. The synaptic contact zone was longer in the SC compared with both the IC and the NC while there was no difference in the synaptic density among the three groups. The somal area of mitral/tufted cells was larger in both the SC and the NC compared with the IC. These results indicate that the exposure to different rearing conditions induces differential morphological changes in both synapses and somata in the AOB of adult hamster.

Animals↗

Effect of perfusate pH on the influx of 5-5'-dimethyl-oxazolidine-2,4-dione and dissociation of epidermal growth factor from the cell-surface receptor: the existence of the proton diffusion barrier in the Disse space.

The influx clearance (PSinf.MID) of the weak acid 5,5'-dimethyl-oxazolidine-2,4-dione (DMO) was determined by the multiple indicator dilution method with the isolated perfused rat liver under various perfusate pH conditions, ranging from 6.4 to 7.6. Although the pH partition theory predicted an increase in influx clearance of ten times in proportion to the change in the unionized fraction of DMO, there was no measurable change in this value. The effect of medium pH on the steady-state cell/medium concentration ratio (C/M) ratio of DMO was also investigated using isolated hepatocytes. The C/M ratio increased while medium pH decreased, but this change was less marked than predicted by the pH partition theory. Finally the pH dependency of the dissociation rate constant (koff) of epidermal growth factor from its receptor was also investigated using both isolated rat hepatocytes and the perfused rat liver. When the extracellular pH was changed from 6.4 to 5.6, the koff value of isolated hepatocytes increased 44 times, while that of the perfused rat liver increased only 9 times. Therefore, the effect of changing the extracellular pH on pH-dependent dissociation of epidermal growth factor from its cell-surface receptor was less in the perfused liver than in isolated hepatocytes. These findings, in addition to the well-known existence of the Na(+)-H+ exchanger on the sinusoidal membrane and the possible existence of the unstirred water layer in the Disse space, seem to suggest the existence of the proton diffusion barrier in the rat liver, which remains stronger in the perfused liver than in isolated hepatocytes.

Animals↗

Application of in vivo microdialysis to transdermal absorption of methotrexate in rats.

Microdialysis was applied to determine the in vivo transdermal absorption of methotrexate (MTX) in rats with or without a new penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). A solution composed of 2.5 mM MTX and 3% (w/v) HPE-101 was applied to the shaved abdomen, in which a semipermeable membrane cannula of 10-mm length was inserted intracutaneously with the use of an L-shaped needle. Intradermal microdialysis was performed at a flow rate of 1.0 microL/min for 12 hr. The concentration of MTX in the dialysate was measured by fluorescence polarization immunoassay (FPIA). HPE-101 (3%, w/v) significantly increased the dermal MTX concentration from 0.06 +/- 0.04 microM in the control to 56 +/- 26 microM in the dialysate from 8 to 12 hr. HPE-101 at concentrations of 0.75, 1.5, 2.25, and 3% (w/v) enhanced the total recovery of MTX in dermal dialysate from 0 to 10 hr by approximately 5, 18, 42, and 500 times compared with the control, respectively. The microdialysis system is useful for assessing in vivo transdermal drug absorption.

Administration, Cutaneous↗

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from industrial rubber products.

3 cases of allergic contact dermatitis from industrial rubber products were investigated using a combination of patch testing in patients and chemical analysis of causative rubber products by gas chromatography (GC), GC-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Our studies revealed N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), a typical rubber allergen, as a causative chemical in a case from a brand of heavy-duty rubber gloves and a case from a black rubber ring for car manufacture, and zinc ethylphenyldithiocarbamate (ZEPC), a dithiocarbamate (DTC)-type accelerator, as a causative chemical in a case from a brand of rubber work gloves: both IPPD and ZEPC, which showed positive patch test reactions, were confirmed in the extracts of the causative rubber products by GC, GC-MS and/or HPLC.

Adult↗