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Biomedical subjects

N Maeda

Publications and source records attributed to N Maeda.

At least 361 records · Page 20Linked to original sources
PubMed1994

Focal spasms in clusters, focal delayed myelination, and hypsarrhythmia: unusual variant of West syndrome.

We report a patient who began to have clusters of seizures characterized by brief elevation of the right arm at 6 months of age. An interictal electroencephalogram (EEG) at 7 months revealed hypsarrhythmia without definite asymmetry. Simultaneous EEG and video recording disclosed that these focal spasms were associated with fast wave bursts superimposed on slow waves most markedly in the left centro-midtemporal region. The patient became seizure-free after synthetic ACTH therapy. The patient is developmentally normal at 3 years 5 months, but magnetic resonance imaging studies revealed findings suggestive of delayed myelination in the left frontal region. This patient is considered to have had an unusual variant of West syndrome associated with focal delayed myelination.

Adolescent↗
PubMed1994

Photosensitive epilepsy in children.

We performed a retrospective analysis of 17 children with photosensitive seizures (PSS) who had been followed for more than 3 years (mean: 9 years). PSS were verified in all patients by simultaneous video-EEG monitoring. The seizures were precipitated by flickering stroboscopes (14 patients) or were induced by patients themselves (3) with head-nodding in front of illumination, blinking at television or close viewing of striped patterns. PSS consisted of myoclonic seizures (eight patients), generalized tonic-clonic convulsions (5), partial seizures (3) or atypical absence (1). According to the International Classification of Epileptic Syndrome, three patients were classified as having severe myoclonic epilepsy in infancy and five as having juvenile myoclonic epilepsy. The remaining nine could not be categorized as any specific epileptic syndrome. Children with age of the onset of epilepsy at 7 years or younger tended to suffer intellectual deficit in addition to intractable seizures.

Adolescent↗
PubMed1994

Deletion and replacement of the mouse adult beta-globin genes by a "plug and socket" repeated targeting strategy.

We describe a two-step strategy to alter any mouse locus repeatedly and efficiently by direct positive selection. Using conventional targeting for the first step, a functional neo gene and a nonfunctional HPRT minigene (the "socket") are introduced into the genome of HPRT- embryonic stem (ES) cells close to the chosen locus, in this case the beta-globin locus. For the second step, a targeting construct (the "plug") that recombines homologously with the integrated socket and supplies the remaining portion of the HPRT minigene is used; this homologous recombination generates a functional HPRT gene and makes the ES cells hypoxanthine-aminopterin-thymidine resistant. At the same time, the plug provides DNA sequences that recombine homologously with sequences in the target locus and modifies them in the desired manner; the plug is designed so that correctly targeted cells also lose the neo gene and become G418 sensitive. We have used two different plugs to make alterations in the mouse beta-globin locus starting with the same socket-containing ES cell line. One plug deleted 20 kb of DNA containing the two adult beta-globin genes. The other replaced the same region with the human beta-globin gene containing the mutation responsible for sickle cell anemia.

Animals↗
PubMed1994

Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression.

Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.

Aging↗
PubMed1994

Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice.

Apolipoprotein E (apo E)-deficient mice are severely hypercholesterolemic and develop advanced atheromas independent of diet. The C57BL/6 strain differs from most inbred strains by having lower HDL concentrations and a high risk of developing early atherosclerotic lesions when fed an atherogenic diet. The relative HDL deficiency and atherosclerosis susceptibility of the C57BL/6 strain are corrected with the expression of a human apolipoprotein AI (apo AI) transgene in this genetic background. To examine if increases in apo AI and HDL are also effective in minimizing apo E deficiency--induced atherosclerosis, we introduced the human apo AI transgene into the hypercholesterolemic apo E knockout background. Similar elevations of total plasma cholesterol occurred in both the apo E knockout and apo E knockout mice also expressing the human apo AI transgene. The latter animals, however, also showed a two- to threefold increase in HDL and a sixfold decrease in susceptibility to atherosclerosis. This study demonstrates that elevating the concentration of apo AI reduces atherosclerosis in apo E deficient-mice and suggests that elevation of apo AI and HDL may prove to be a useful approach for treating unrelated causes of heightened atherosclerosis susceptibility.

Animals↗
PubMed1994

Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption.

With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet. The other six normals had no lesions. Our study demonstrates that heterozygous mice with only one functional apo E gene are more susceptible to diet-induced atherosclerosis than are normal, two-copy mice. Genetically determined quantitative limitations of apo E could, therefore, have similar effects in humans when they are stressed by an atherogenic diet.

Animals↗
PubMed1994

A screening concept based on a hypothesis led to the development of a putative cognitive enhancer that stimulates penile erection.

Starting from the hypothesis that drugs which specifically activate the hippocampal cholinergic nerve activity may ameliorate memory impairments, we carried out a series of evaluations for a novel cognitive enhancer using enhancement of penile erection as a sign of cholinergic activation, and found FR64822. The compound facilitated penile erection in naive rats, and it ameliorated scopolamine-induced amnesia of rats in passive avoidance tasks with bell-shaped dose-response curves, while it dose-dependently reduced body weight gain in Zucker fatty rats. Pretreatment with sulpiride (32 mg/kg, p.o.) hardly affected the former two activities, but significantly reduced the anorectic activity in Zucker rats. Further evaluation of FR64822 derivatives characterized a second compound, FR121196, which induces penile erection and memory enhancement, but not body weight reduction. Memory enhancing and erection stimulating activities of FR121196 were abolished in rats treated with either cysteamine (200 mg/kg, s.c.), a somatostatin depletor, or lesioning of the serotonergic raphe nuclei. Thus, classic whole animal studies based on a hypothesis proved to be efficient for reaching our objective, the discovery of a new drug. They also gave us insight into the common somatostatinergic and serotonergic mechanisms underlying penile erection and memory improvement.

Animals↗
PubMed1994

Role of the dopaminergic, serotonergic and cholinergic link in the expression of penile erection in rats.

The neural mechanisms underlying the penile erection induced by serotonergic, cholinergic and dopaminergic stimulants were comparatively investigated. Fenfluramine (0.1-10 mg/kg, i.p.), pilocarpine (0.032-3.2 mg/kg) and apomorphine (0.01-1 mg/kg) induced penile erection in rats with bell-shaped dose-response curves. The penile erection induced by fenfluramine (1 mg/kg) was dose-dependently antagonized by pindolol (0.1-3.2 mg/kg), a 5-HT1 antagonist, or scopolamine (0.032-1 mg/kg), a muscarinic antagonist, but not by sulpiride (1-32 mg/kg), a dopaminergic antagonist. The penile erection induced by pilocarpine (0.32 mg/kg) was countered by pindolol or scopolamine but not by sulpiride, while that induced by apomorphine (0.032 mg/kg) was countered by all three antagonists. Septo-hippocampal cholinergic deafferentations by medial septum lesioning or fimbria-fornix transection also significantly attenuated the penile erection induced by fenfluramine or apomorphine, but scarcely affected that induced by pilocarpine. Raphe lesion by injections of 5,7-dihydroxytryptamine, a serotonergic neurotoxin, into the median- and dorsal-raphe nuclei significantly attenuated the penile erections induced by fenfluramine and apomorphine but not that by pilocarpine. These results suggest that a neuronal link between the dopaminergic, serotonergic and cholinergic systems plays a crucial role in the expression of penile erection; dopaminergic stimulation causes an activation of the raphe serotonergic neurons which in turn enhances the septo-hippocampal cholinergic pathway and results in expression of penile erection.

Animals↗
PubMed1994

Detection of immunoglobulin binding factor by enzyme-linked immunosorbent assay using two monoclonal antibodies.

Immunoglobulin binding factor (IgBF) found in human seminal plasma may be involved in suppressing antibody production against sperm in the female and male genital tracts. In the present study an enzyme-linked immunosorbent assay (ELISA) for IgBF was developed using monoclonal anti-IgBF antibodies. The sensitivity of the method was 20 pg/ml. The method was used to quantify IgBF in sera from women. In addition high levels of IgBF was found in cervical mucus of the uterus and in bronchial washings. The present results suggest that IgBF is found in tissues that are exposed to the external environment and may be a component of the local immunity system.

Adult↗
PubMed1994

[Studies on auditory brainstem responses showing absence or significantly poor formation of waves II-V in children].

We performed a retrospective study on 7 children in whom the auditory brainstem responses (ABR) showed absence or significantly poor formation of waves II-V. Two patients had degenerative diseases that affected the brains diffusely. In the remaining 5 patients, the symptoms consisted of action tremor (3 patients) or pyramidal signs (2 patients). There were neither clinical signs nor neuroimaging findings suggesting brainstem involvements. The evolutional changes of the ABRs had a good correlation with the clinical course. Absence or significantly poor formation of waves II-V of ABR occurs in various diseases and may not necessarily reflect severe organic brain lesions.

Brain Diseases↗
PubMed1994

Occipital roof development in the Japanese musk shrew, Suncus murinus.

The occipital squama of the Japanese musk shrew, Suncus murinus, consists only of membrane bone which arises from the periosteal bony band of the supraoccipital cartilage. No cartilaginous tectum posterius, generally forming the dorsal border to the foramen magnum, was found in the developing chondrocranium. Also additional intramembranous ossification centres were occasionally observed, and could be interpreted as being the primordium of the interparietal bone. These observations indicate that the membrane bone is homologous not with the interparietal bone but with the tectum posterius, i.e. the membranous supraoccipital bone. This is an instance of interchangeability between cartilage and membrane bone in a mammal.

Animals↗
PubMed1994

A mechanism of 5-HT3 receptor mediation is involved etiologically in the psychological stress lesion the stomach of the mouse.

The role of brain amines, possibly involved in psychological stress, was evaluated and we postulate that the 5-hydroxytryptamine 5-HT3 receptors in the central nervous system are involved in the gastric lesion formation by psychological stress. The stress was in a communication box paradigm, in which each nonshocked mouse (responder) was placed in a Plexiglas compartment adjacent to mice receiving electrical shocks (sender). The responder mice revealed rather depressed gastric secretion, but developed gastric lesions which are significantly attenuated by pretreatment of dl-p-chlorophenylalanine methyl ester:HCl (PCPA; 200-400 mg/kg p.o.), but not 6-hydroxydopamine (6-OH-DA; 60 micrograms/body i.c.v. or 80 mg/kg i.p. 1 hr after a 20-mg/kg i.p. dose of desipramine). Oral treatment with GR38032F (0.01-1 mg/kg), ICS205-930 (0.01-20 mg/kg), MDL72222 (0.01-1 mg/kg), metoclopramide (0.1-100 mg/kg), ketanserin (0.01-10 mg/kg) and sulpiride (32-320 mg/kg) dose-dependently attenuated the psychological stress lesion formation, and the activity was arranged in the order of their in vitro binding affinities for the 5-HT3, but not 5-HT1A or 5-HT2 receptors. In contrast, a peripherally acting 5-HT3 antagonist, M-840 ([[3-(1-methyl-1H-indol-3-yl)-1,2,4-oxadiazol-5- yl]-methyl]trimethyl-ammonium iodide), dopamine acting compounds, haloperidol and FR64822 [N-(4-pyridylcarbamoyl)amino-1,2,3,6- tetrahydropyridine), and antisecretory drugs, atropine and famotidine, minimally affected the lesion formation.

Animals↗
PubMed1994

Keratoconus and contact lens-induced corneal warpage analysis using the keratomorphic diagram.

PURPOSE: Videokeratography of early keratoconus may be difficult to distinguish from contact lens-induced corneal warpage, even by experienced examiners. Furthermore, topographic irregularity may be judged inconsistently if quantitative standards are not applied. Quantitative measures based on videokeratographic data were developed and evaluated to determine if improved corneal topographic classification can be achieved. METHODS: The Corneal Irregularity Coefficient (CIC) and Corneal Power Coefficient (CPC) were derived from multiple measures of mean corneal power and its variance for 207 videokeratographs of normal, warped, keratoconus, and keratoconus-suspect corneas. CIC was plotted against CPC, creating a distribution of points representing all maps that tended to be grouped according to surface conditions (the Keratomorphic Diagram). Normal, steep, abnormal, and warped zones were defined by CIC and CPC cutoff values chosen to distinguish normal from keratoconus corneas graphically. RESULTS: Seventy of 76 normal corneas were grouped in the normal zone and 6 in the steep zone; 84 of 84 keratoconus corneas were grouped in the abnormal zone; 35 of 35 contact lens-induced warpage cases were grouped in the warped zone; and 10 of 12 keratoconus-suspect corneas were grouped in the warped zone, with 2 in the abnormal zone. Serially plotted data of keratoconus progression and warpage regression demonstrated that the vector displacement of CIC and CPC values may provide a potentially useful means of distinguishing contact lens-induced warpage from keratoconus-suspect corneas. CONCLUSION: The Keratomorphic Diagram aids in classifying and comparing corneal shape by plotting indices along axes with easily recalled scales. The diagram may become a useful tool to assess presurgical corneal surface instability and postoperative progression of corneal shape change due to healing.

Contact Lenses↗
PubMed1994

Non-isotopic restriction mapping of cosmid DNA.

A protocol for the non-isotopic restriction mapping of cosmid DNA was developed. After digestion with lambda terminase and partial digestion with restriction enzymes, DNA fragments containing right or left cohesive cos termini were selectively captured by hybridization with biotinylated oligonucleotides, bound to magnetic beads coated with streptavidin and recovered by heating. Recovered DNA fragments containing cos ends were resolved by agarose gel electrophoresis, and fluorescence from the DNA fragments in the ethidium bromide-stained gel was detected with the fluorescent image analyzer, FMBIO. Restriction maps were directly determined from the ladder of the partial digestion products. Two micrograms of cosmid DNA for each partial digestion were sufficient for mapping the restriction enzyme sites. This procedure provides a prototype for other cos sequence-mediated or other specific sequence-mediated DNA isolation technologies and a convenient method for non-isotopic DNA analysis. The rapid physical analysis of cosmid DNA that we present here will contribute to large DNA structural analyses like the human genome project.

Base Sequence↗
PubMed1994

Alteration of corneal asphericity in rigid gas permeable contact lens induced warpage.

We developed the corneal asphericity index (CAI), which indicates the asphericity of the central cornea using the TMS-1 videokeratoscope, and used the CAI to evaluate both normal corneas and corneas with rigid gas permeable (RGP) lens induced warpage. The CAI (mean +/- standard deviation) for the 22 control corneas was 0.33 +/- 0.26, which indicates that the normal central cornea has a prolate shape. The average CAI for the 24 corneas with RGP lens induced warpage was significantly lower (-0.15 +/- 0.36, P = 0.0001). These data suggest that some corneas have abnormal asphericity in the central cornea when warpage occurs with RGP lenses. CAI is useful for the quantitative assessment of asphericity and topographic abnormalities in the central cornea caused by contact lens induced warpage.

Adult↗
PubMed1994

Automated keratoconus screening with corneal topography analysis.

PURPOSE: Although visual inspection of corneal topography maps by trained experts can be powerful, this method is inherently subjective. Quantitative classification methods that can detect and classify abnormal topographic patterns would be useful. An automated system was developed to differentiate keratoconus patterns from other conditions using computer-assisted videokeratoscopy. METHODS: This system combined a classification tree with a linear discriminant function derived from discriminant analysis of eight indices obtained from TMS-1 videokeratoscope data. One hundred corneas with a variety of diagnoses (keratoconus, normal, keratoplasty, epikeratophakia, excimer laser photorefractive keratectomy, radical keratotomy, contact lens-induced warpage, and others) were used for training, and a validation set of 100 additional corneas was used to evaluate the results. RESULTS: In the training set, all 22 cases of clinically diagnosed keratoconus were detected with three-false-positive cases (sensitivity 100%, specificity 96%, and accuracy 97%). With the validation set, 25 out of 28 keratoconus cases were detected with one false-positive case, which was a transplanted cornea (sensitivity 89%, specificity 99%, and accuracy 96%). CONCLUSIONS: This system can be used as a screening procedure to distinguish clinical keratoconus from other corneal topographies. This quantitative classification method may also aid in refining the clinical interpretation of topographic maps.

Cornea↗