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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 361 records · Page 20Linked to original sources

Multicenter study of paroxysmal dyskinesias in Japan--clinical and pedigree analysis.

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal-dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion-induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

Adolescent↗

A role of migratory Schwann cells in a conditioning effect of peripheral nerve regeneration.

The common peroneal nerve in mice was conditioned by axotomy around the head of the fibula. At various intervals from 1 day to 2, 3, 5, 15, and 25 days, a test lesion was made by axotomy 15 mm proximal to the conditioning lesion site. The proximal stump of the transected nerve was sandwiched between two sheets of thin plastic film and remained in vivo for various intervals from 3 h to 6, 9, 12, 24, 48, 72 and 96 h. The regenerating axons were visualized on the film with silver nitrate impregnation. Schwann cells were visualized migrating onto the film using immunohistochemistry with anti-S-100. To determine the effects of migratory Schwann cells on axonal outgrowth, a film model was established on one limb. After the nerve stump was removed from the film, the treated film was transferred to a new lesion on the contralateral limb and 2 days later the film was harvested for histological examination. Conditioned by a prior axotomy more than 3 days earlier, regenerating axons sprouted within less than 1 h after the test lesion was established and grew naked at five times higher rate: The growth rate was similar to that observed during regeneration in the presence of migratory Schwann cells (ordinary type). After a short interval, the axons, which had been ensheathed by migratory Schwann cells (reactive type), continued growing at a significantly (P < 0.01) higher rate. The reactive type of cells had fewer numbers of branches and higher activity in promoting axonal outgrowth than the ordinary type. Thus, both ordinary and reactive types of cells played key roles in initiating and maintaining a conditioning effect, respectively.

Animals↗

Negative chronotropic and inotropic effects of class I antiarrhythmic drugs assessed in isolated canine blood-perfused sinoatrial node and papillary muscle preparations.

The present study was designed to assess the negative chronotropic and inotropic effects of 10 class I antiarrhythmic drugs, using isolated canine blood-perfused sinoatrial node and papillary muscle preparations. Each drug showed negative chronotropic and inotropic effects in a dose-related manner. The potency of the suppressive effect on the sinoatrial automaticity was in the order of aprindine, quinidine, flecainide, lidocaine, mexiletine, cibenzoline, disopyramide, procainamide, tocainide, and phenytoin, while the effect on the ventricular contraction was in the order of aprindine, flecainide, cibenzoline, lidocaine, mexiletine, disopyramide, tocainide, phenytoin, quinidine, and procainamide. The differences in the suppressive effects could not necessarily be explained by their subclassification, based either on action potential duration or kinetic properties of dissociation or association with sodium channels. On the other hand, we found a good correlation between the negative inotropic effects of class I drugs in this study and the canine antiarrhythmic plasma concentrations for the digitalis- and coronary ligation-induced ventricular arrhythmia models in our previous studies. However, the negative chronotropic effects of the drugs showed a poor correlation with the antiarrhythmic plasma drug concentrations. The data shown in this paper may provide a convenient guideline for predicting acute cardiosuppressive effects of antiarrhythmic drugs, especially in patients with reduced cardiac function.

Animals↗

Solid cystic tumor of the pancreas in elderly men: report of a case.

Solid cystic tumor of the pancreas is a primary pancreatic neoplasm of unknown etiology that most commonly occurs in young women and ordinarily contains hemorrhagic tissue. We report herein the unusual case of a 75-year-old man found to have a solid cystic tumor in the body and tail of the pancreas, who is the oldest such male patient to be documented in Japan. The results of laboratory data and imaging studies indicated that the patient had a nonfunctioning islet tumor or solid cystic tumor of the pancreas, and distal pancreatectomy with splenectomy was performed. The diagnosis of solid cystic tumor was confirmed based on macroscopic and histological findings of the resected pancreatic tumor. The patient is currently in good health, without any signs of tumor recurrence 1 year and 4 months after his operation. A total of 181 cases of solid cystic tumors of the pancreas reported in the Japanese literature, including our case, were reviewed to evaluate the clinical differences between patients aged 50 years or over and those younger than 50 years.

Aged↗

A rat model of human T lymphocyte virus type I (HTLV-I) infection: in situ detection of HTLV-I provirus DNA in microglia/macrophages in affected spinal cords of rats with HTLV-I-induced chronic progressive myeloneuropathy.

To investigate the pathogenetic role of human T lymphocyte virus type I (HTLV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been established. Wistar-King-Aptekman-Hokudai strain rats with induced HTLV-I infection develop a chronic progressive myeloneuropathy with paraparesis of hind limbs after an incubation period of 15 months. In the affected spinal cord in these rats, white matter degeneration, demyelination and vacuolar change with microglia/macrophage infiltration are present as are the provirus DNA and the virus mRNA. To identify infected cells in the affected lesions, we carried out in situ hybridization of amplified fragments of the provirus DNA by polymerase chain reaction on thin sections, plus immunohistochemistry on the same sections. The provirus DNA was localized in some microglia/macrophages in the spinal cord lesion. In addition, the HTLV-I provirus was clearly evident not only in ED-1-negative lymphoid cells but also in ED-1-positive macrophages from lymph nodes. These observations suggest that cells of microglia/macrophage lineage may be one of dominant viral reservoirs in the spinal cords and lymph nodes in HAM rat disease. These infected microglia/macrophages may relate to cause the myeloneuropathy through neurotoxic cytokine synthesis.

Animals↗

Adult onset limb-girdle type mitochondrial myopathy with a mitochondrial DNA np8291 A-to-G substitution.

We analyzed mitochondrial DNA (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.

Adult↗

Antineutrophil cytoplasmic antibody in patients with primary Sjögren's syndrome.

The incidence, specificity and clinical significance of positivity for serum antineutrophil cytoplasmic antibody (ANCA) was investigated in 60 patients with primary Sjögren's syndrome (SjS). The indirect immunofluorescence (IIF) technique and an enzyme-linked immunosorbent assay (ELISA) were used to measure ANCA. Purified myeloperoxidase (MPO), lactoferrin (LF), cathepsin-G (CTG) and elastase (HLE) served as ANCA antigens for the ELISA. Ten (16.7%) of the 60 SjS patients showed positivity by IIF for perinuclear, but not cytoplasmic, ANCA. Four of the 60 sera were shown to be positive for LF, four for MPO, 0 for CTG and 0 for HLE by ELISA. There was no correlation between ANCA positivity and clinical features. ANCA in patients with SjS might be an epiphenomenon of polyclonal B-cell activation.

Adult↗

Silicone prosthesis prevents vertigo due to the defect at the mastoid process after mastoidectomy: a clinical report.

This clinical report describes a 64-year-old woman with a bony defect in the mastoid process after mastoidectomy and who experienced vertigo on cold and windy days during winter. The patient noticed that packing a piece of paper or cotton into the defect prevented the vertigo. The patient refused surgical repair, so a silicone prosthesis was fabricated to fill the defect completely. Electronystagmography confirmed the effectiveness of the prosthesis to prevent nystagmus. Although surgical repair is ideal, prosthesis repair of the defect may prove to be effective in some patients.

Electronystagmography↗

Exposure with the environmental estrogen bisphenol A disrupts the male reproductive tract in young mice.

Environmental estrogens (endocrine disruptive chemicals) have been shown to affect reproduction in wild life and it has been reported that maternal exposure with those chemicals have adverse effects on the male reproductive tract. However, little is known about the potential effects of prepubertal or pubertal exposure with environmental estrogens on the male reproductive tract. Here we examine plasma hormone levels and histology in the testis of mice following either 4- or 8-week oral administration of bisphenol A. Plasma free testosterone levels were dramatically decreased following 8 weeks of bisphenol A treatment compared with control group and morphologically multinucleated giant cells having greater than three nuclei were found in seminiferous tubules in the testis following the 8-week bisphenol A treatment. No differences in plasma corticosterone and luteinizing hormone levels were seen between bisphenol A and control groups. Thus, exposure with bisphenol A around pubertal period may directly disrupt the male reproductive tract. These facts suggest that more detailed studies will warrant the assessment of the risk to the developing human testis from exposure to bisphenol A and other environmental estrogens in prepubertal and pubertal period.

Administration, Oral↗

Screening for variants of the uncoupling protein 2 gene in Japanese patients with non-insulin-dependent diabetes mellitus.

We examined genetic mutations in the coding regions of the uncoupling protein 2 (UCP2) gene in 100 patients with non-insulin-dependent diabetes mellitus (NIDDM). The sequences of each exon-intron boundary were detected by polymerase chain reaction (PCR) using specific primer pairs designed in the cDNA sequence of UCP2 and a cycle-sequence method. Using the specific primer pairs in the intron 5'- or 3'-untranslated region, each exon with its exon-intron boundaries was amplified with the PCR method, and the PCR products were analyzed using a single-strand conformation polymorphism (SSCP) method. One nucleotide substitution in exon 4 was found, which exchanged Ala (gcc) at position 55 of the amino acid sequence for Val (gtc), previously reported in Denmark by Urhammer et al in 1997. The polymorphism was reanalyzed in all patients and 120 normal subjects using a PCR-restriction fragment length polymorphism method. There was no difference in the genotype distribution between patients and normal subjects, and our genotype distribution was similar to the Danish study. Furthermore, there were no clinical differences between genotype groups among the patients. No other mutation including the exon-intron boundary was found in these patients. Genetic mutations of UCP2 may not be commonly associated with obesity or diabetes in Japanese subjects.

Adult↗

Characteristics of accommodation toward apparent depth.

This paper deals with characteristics of accommodation evoked by perceived depth sensation and the dynamic relationship between accommodation and vergence, applying newly developed optical measurement apparatuses. A total of five subjects looked at three different two-dimensional stimuli and two different three-dimensional stimuli; namely a real image and a stereoscopic image. With regard to the two-dimensional stimuli, a manifest accommodation without any accompanying vergence was found because of an apparent depth sensation even though the target distance was kept constant. With regard to the three-dimensional stimuli, larger accommodation and clear vergence were evoked because of binocular parallax and a stronger depth sensation. As for the stereoscopic image, a manifest overshoot (the accommodation peaked first and receded considerably) was found while the vergence remained constant. On the other hand, the overshoot of accommodation was smaller when subjects were watching the real image. These results reveal that brain depth perception has a higher effect on accommodation than expected. The relationship of accommodation and vergence toward the stereoscopic image suggests a reason why severe visual fatigue is commonly experienced by many viewers using stereoscopic displays. It has also paved the way for the numerical analysis of the oculomotor triad system.

Accommodation, Ocular↗

Proteolysis of neuronal cell adhesion molecule by the tissue plasminogen activator-plasmin system after kainate injection in the mouse hippocampus.

Tissue plasminogen activator (tPA) is a serine protease that converts inactive plasminogen to the active protease plasmin and mediates extracellular metabolism. tPA is transcriptionally induced in the mouse hippocampus by pharmacological or electrical stimulation of neuronal activity and mediates excitotoxin-induced neuronal degeneration. Therefore, we hypothesized that tPA would be induced in the hippocampus after kainic acid (KA) injection into the lateral cerebral ventricle (LCV) and that the activated tPA-plasmin system would degrade the neuronal cell adhesion molecule (NCAM), which is a component of the extracellular matrix. In order to investigate this possibility, we first examined whether NCAM is a substrate for the tPA plasmin system by incubating mouse brain homogenates with tPA and plasminogen at 37 degrees C. Next, we examined the degradation of NCAM and the changes of tPA activity in the mouse hippocampus with immunohistochemical procedures and histological zymography after KA injection into both LCVs. As a result, we observed neuronal atrophy and a decrease of NCAM immunoreactivity along with an increase of tPA activity in the CA3 area of the hippocampus. These results suggest that activation of the tPA plasmin system after KA injection into the LCVs results in the degradation of NCAM in the CA3 area.

Animals↗

Utilization of a model lung system to assess the effects of an inspiratory impedance threshold valve on the relationship between active decompression and intra-thoracic pressure.

Use of an inspiratory impedance valve has recently been shown to increase the efficacy of standard and active compression-decompression cardiopulmonary resuscitation. We evaluated the effects of a prototypic impedance valve on the relationship between the active decompression and intra-thoracic pressure using a mechanical model lung system. Intermittent impedance to inspiratory flow of respiratory gases during the decompression phase of active compression-decompression cardiopulmonary resuscitation significantly decreased the intra-thoracic pressure, while the pressure was almost zero cm H2O during the cardiopulmonary resuscitation cycle when the impedance threshold valve was not functioning. Thus, this mechanical model will help in evaluating the valve as well as in optimizing its function by simulating various forms of lung disease.

Cardiopulmonary Resuscitation↗

Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants.

The amounts of aristolochic acid I and II in four groups of medicinal plants from the Aristolochiaceae and some related plants were determined by high-pressure liquid chromatography, for Aristolochia was reported to produce interstitial nephritis caused by aristolochic acids during chronic use for the treatment of rheumatism, diuretic and analgesic. They were detected in all the plants that originated from the genus Aristolochia (Aristolochiaceae) and in some of the plants from the genus Asarum (Aristolochiaceae). The present results suggest that these medicinal plants should be prohibited to use for remedy due to the harmful effects attributed to aristolochic acids.

Aristolochic Acids↗

Clinical and immunological significance of neopterin measurement in cerebrospinal fluid in patients with febrile convulsions.

Neopterin is synthesized mainly by monocytes/macrophages and is considered to be a marker for activation of the cellular immune system. It has been reported that cerebrospinal fluid (CSF) neopterin levels are significantly higher in patients with bacterial meningitis than in those with aseptic meningitis or non-pleocytotic CSF. In this study levels of neopterin and interferon-gamma (IFN-gamma) were measured in children with non-pleocytotic CSF. The CSF neopterin levels were significantly higher in patients with typical febrile convulsions (FCs) (15.0 +/- 4.5 nmol/l) than in those with pyrexia without convulsions (6.5 +/- 2.7 nmol/l) or convulsions without pyrexia, namely, epilepsy (4.8 +/- 2.4 nmol/l). The CSF neopterin/serum neopterin ratio (C/S ratio) was also higher in patients with typical FCs (1.54 +/- 0.83) than in those with pyrexia without convulsions (0.32 +/- 0.18) or convulsions without pyrexia (0.77 +/- 0.28). Patients with prolonged FCs tended to have higher CSF neopterin levels than those with typical FCs. There was also a tendency for CSF IFN-gamma levels to be higher in patients with FCs than in those with pyrexia without convulsions or convulsions without pyrexia. The results of the present study suggest that some immune activation in the central nervous system (CNS) compartment may be related to the mechanisms of FCs.

Child, Preschool↗

Corticotropin-releasing factor plays a permissive role in cerebellar long-term depression.

This study of rat cerebellar slices yielded two lines of evidence indicating that the corticotropin-releasing factor (CRF) found in climbing fibers (CFs) is critical for the induction of long-term depression (LTD) at the parallel fiber (PF) synapses of Purkinje cells (PCs) by their conjunctive activation with either stimulation of CFs or depolarization of PCs. First, LTD induction was effectively blocked by specific CRF receptor antagonists, alpha-helical CRF-(9-41) (alpha-h CRF) and astressin; and second, LTD was no longer observed in CF-deprived cerebella but was restored by CRF replenishment. The data obtained in this study suggest that these effects are mediated by protein kinase C (PKC) and not by Ca2+ signaling or cyclic GMP (cGMP) production.

Animals↗