Significance of chronic cough as a defence mechanism or a symptom in elderly patients with aspiration and aspiration pneumonia.
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Aged↗
Biomedical subjects
R Namba
Publications and source records attributed to R Namba.
Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the copper/zinc superoxide dismutase gene showing mild clinical features and lewy body-like hyaline inclusions.
BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation between the clinical and pathological features and the various SOD1 gene mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS. DESIGN: Clinical histories and neurological findings, gross and microscopic pathological features, and DNA analysis of the SOD1 gene. RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients showed slower disease progression and lack of upper motor neuron signs. Neuropathologically, the autopsied patient showed the form of familial ALS with posterior column involvement, and the pontocerebellar tract and the dentate nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like hyaline inclusions were observed in the affected motor and nonmotor neurons. CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron signs. We believe that Leu126Ser might be associated with the clinical features and that the mutation site in the SOD1 gene and disease duration might be associated with the formation of Lewy body-like hyaline inclusions.
Adult↗
Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy).
Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.
Adult↗
Photoactivated gene expression for cell fate mapping and cell manipulation.
A long-standing goal of developmental biologists is to create developmental fate maps by tracking individual cells through development. Another objective is to perturb the behavior of selected cells and follow the ensuing effects. To this end, we have developed a technique that allows for spatial and temporal control of gene expression in single cells or patches of cells using light to induce gene expression. This technique relies on "caging" the activity of the potent transcriptional activator GAL4VP16 with a photolabile compound, which can be removed with a brief exposure to long-wavelength ultraviolet (UV) light. The caged GAL4VP16 is injected into early-stage embryos, which are aged to the desired point in development, and the cell(s) of interest are irradiated with a brief pulse of long-wavelength UV light. This method has been used extensively in Drosophila, Xenopus, and Zebrafish embryos. The methods for purifying, caging, injection, and photoactivation of the GAL4VP16 protein, and methods for the visualization of marked cells are described in detail.
Animals↗
Mutations in the alpha-tubulin 67C gene specifically impair achiasmate segregation in Drosophila melanogaster.
Drosophila melanogaster oocytes heterozygous for mutations in the alpha-tubulin 67C gene (alphatub67C) display defects in centromere positioning during prometaphase of meiosis I. The centromeres do not migrate to the poleward edges of the chromatin mass, and the chromatin fails to stretch during spindle lengthening. These results suggest that the poleward forces acting at the kinetochore are compromised in the alphatub67C mutants. Genetic studies demonstrate that these mutations also strongly and specifically decrease the fidelity of achiasmate chromosome segregation. Proper centromere orientation, chromatin elongation, and faithful segregation can all be restored by a decrease in the amount of the Nod chromokinesin. These results suggest that the accurate segregation of achiasmate chromosomes requires the proper balancing of forces acting on the chromosomes during prometaphase.
Animals↗
Fate mapping of Drosophila embryonic mitotic domain 20 reveals that the larval visual system is derived from a subdomain of a few cells.
In an attempt to study the fates of cells in the dorsal head region of Drosophila embryos at gastrulation, we used the photoactivated gene expression system to mark small numbers of cells in selected mitotic domains. We found that mitotic domain 20, which is a cluster of approximately 30 cells on the dorsal posterior surface, gives rise to various ectodermal cell types in the head, including dorsal pouch epithelium, the optic lobe, and head sensory organs, including Bolwig's organ, the larval photoreceptor organ. We found that the optic lobe and larval photoreceptors share the same origin of a few adjacent cells near the center of mitotic domain 20, suggesting that within the mitotic domain, there is a subdomain from which the larval visual system is specified. In addition to the components of the larval visual system, this central region of mitotic domain 20 also generates a part of the eye-antennal disc placode; cells that gives rise to the adult visual system. We also observed that a significant amount of cell death occurred within this domain and used cell ablation experiments to determine the ability of the embryo to compensate for cell loss.
Animals↗
Direct determination of bisphenol A and nonylphenol in river water by column-switching semi-microcolumn liquid chromatography/electrospray mass spectrometry
A rapid and sensitive analytical method based on column-switching semi-microcolumn high-performance liquid chromatography (HPLC) with electrospray mass spectrometry was developed for determining trace levels of bisphenol A (2,2-bis(4-hydroxyphenyl)propane) and nonylphenol (4-nonylphenol) in river water. An aliquot of sample solution was directly injected into the precolumn packed with Capcellpak MF-Ph for sample cleanup and enrichment. The compounds of interest were then transferred to a C-18 analytical column for main separation through a change in flow path by a programmed switching valve. Bisphenol A, nonylphenol, and interfering substances were satisfactorily separated with a simple gradient elution complete within 35 min. Detection of their deprotonated molecules was conducted in negative ion mode. A reduced flow rate (100 &mgr;L/min) optimized for the narrow bore column was found advantageous in obtaining a high degree of sensitivity during electrospray detection. The influence of carrier additives on sensitivity was also examined. This method produced detection limits of 0.5 ng/mL for bisphenol A and 10 ng/mL for nonylphenol (signal-to-noise ratio 3). Calibration curves were observed in the range of 2.5-50 ng/mL (r(2) = 0.999) for bisphenol A and 50-500 ng/mL (r(2) = 0.998) for nonylphenol. Recoveries of the compounds from spiked distilled water and river water were 99.7-138.5% with a relative standard deviation (RSD) ranging from 2.2-9.7%. Copyright 1999 John Wiley & Sons, Ltd.
Journal Article↗
Esophageal varices before and after endoscopic variceal ligation: evaluation using helical CT.
The purpose of this study was to demonstrate the utility of helical CT in assessing the therapeutic effects of endoscopic variceal ligation (EVL). Twenty-four patients with esophageal varices were examined. Helical scanning was initiated 60 s after intravenous injection (Iopamidol 300 mgI/ml, total 120 ml, 3 ml/s) was started. Esophageal varices were clearly depicted as high-density areas. Multiplanar reformation and 3D images demonstrated collateral circulation three-dimensionally. After EVL, mucosal high-density areas had diminished markedly, but collateral veins around the esophagus, and gastro- and/or spleno-renal shunts, were unchanged in all patients. Of 21 patients with collateral circulation, esophageal varices recurred endoscopically in 6 patients within 12 months. In 3 patients without collateral circulation, esophageal varices did not recur within 12 months. From these findings, we conclude that helical CT is a useful method for assessing the therapeutic effects of EVL.
Collateral Circulation↗
Accumulation of milky fluid: a late complication of cataract surgery.
We describe 3 patients who presented with an accumulation of homogeneous milky fluid in the capsular bag several years after continuous curvilinear capsulorhexis, phacoemulsification, and posterior chamber intraocular lens (IOL) implantation. In each case, the entire edge of the anterior capsule opening was tightly attached to the peripheral IOL optic. The milky fluid was present in the closed chamber between the IOL optic and the posterior capsule. The fluid was sampled in 2 patients, and its concentration of sodium hyaluronate was determined by high-performance liquid chromatography. The concentration of sodium hyaluronate resembled that in normal aqueous humor. In 1 case, the protein concentration was measured and found to be elevated. Electrophoresis showed that human serum albumin was the main protein constituent. While the outcome was favorable in all 3 patients, this delayed complication of cataract surgery merits further study to clarify its etiology and pathogenesis.
Aged↗
Migration of polyethylene particles around stable implants in an animal model.
The aim of this study was to test the hypothesis that a tight seal between bone and implant will eliminate the avenue of particle migration around stable implants. Three types of implants were used in rabbits (polished press-fit Ti-6Al-4V or plasma-sprayed hydroxyapatite [HA]-coated Ti-6Al-4V) or doughy stage polymethyl methacrylate (PMMA). Implants were placed in the condylar notch. Each animal received an intra-articular injection of high density polyethylene (PE) particles (10(8) in 0.4 mL; mean size 4.7 microns) at 4 and 6 weeks postoperatively. Eight weeks postoperatively, peri-implant tissues were examined for PE particles and osteolysis. In all cases, intracellular PE particles were seen at the bone-implant interface and within marrow. No osteolysis was observed. Bone apposition was determined by computerized image analysis. There was no significant difference in the percentage of bone apposition (+/- SD) among the three groups of implants: Ti-6Al-4V (68% +/- 19%), HA-coated Ti-6Al-4V (70% +/- 10%), and PMMA (59% +/- 12%). These results indicate that a polished Ti-6Al-4V surface is as effective as PMMA or HA coating in limiting migration of PE particles around stable osseointegrated implants in rabbits.
Alloys↗
Evaluation of uptake and release of technetium-99m MIBI SPECT of pulmonary and mediastinal lesions.
We evaluated the uptake and release of Tc-99m MIBI in 7 benign and 30 malignant pulmonary and mediastinal lesions. Of the 37 patients, 13 underwent surgery; malignant involvement was examined in 21 mediastinal lymph nodes. Tl-201 SPECT was also performed in 10 patients. Tc-99m MIBI SPECT studies were performed on transverse SPECT images acquired 30 minutes and 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A). Regions of interest were set in the area of abnormal uptake of Tc-99m MIBI and in an area of normal tissue in the contralateral lung. The uptake ratio of the lesion in the contralateral normal lung was obtained on the early image (early ratio; ER) as well as the delayed image (delayed ratio; DR). The benign lesions showed significantly lower ER (1.6 +/- 0.3) and DR (1.4 +/- 0.4) than the malignant lesions (1.9 +/- 0.5 and 1.8 +/- 0.5, respectively; both p < 0.05). There was no significant difference in the retention index (RI), calculated as RI = (DR-ER)/ER x 100. The DR obtained with Tl-201 SPECT images was significantly higher than that obtained with Tc-99m MIBI SPECT (p < 0.05). For the detection of mediastinal lymph node metastases, the early images showed sensitivity, specificity, and accuracy of 85.7%, 100%, and 95.2%, respectively, for the delayed images these values were 85.7%, 92.9%, and 90.5%, respectively. These results suggest that the uptake ratio of Tc-99m MIBI is a useful index in assessing benign or malignant pulmonary and mediastinal lesions.
Aged↗
The influence of long-term treatment with povidone-iodine on thyroid function.
Povidone-iodine (PVP-I) is generally very safe, but cases of thyroid dysfunction induced by PVP-I have been reported. The effect of long-term treatment with PVP-I on thyroid function was to be assessed. In 40 inpatients of the department of neurology, the status of the use of PVP-I preparations and their effects on serum inorganic iodine levels and thyroid functions were investigated. In 27 patients treated with PVP-I for a long term, inorganic iodine levels were significantly increased as compared to those in 13 patients without PVP-I treatment. Out of 27 patients treated with PVP-I in the long term, subclinical hypothroidism was seen in 3 patients, mild hyperthroidism was seen in 1 patient, and subclinical hyperthyroidism was suspected in 7 patients. Patients treated with PVP-I for a long time should be observed carefully for any manifestation of thyroid dysfunction.
Amyotrophic Lateral Sclerosis↗
Drosophila embryonic pattern repair: how embryos respond to bicoid dosage alteration.
The product of the maternal effect gene, bicoid (bcd), is a transcription factor that acts in a concentration-dependent fashion to direct the establishment of anterior fates in the Drosophila melanogaster embryo. Embryos laid by mothers with fewer or greater than the normal two copies of bcd show initial alterations in the expression of the gap, segmentation and segment polarity genes, as well as changes in early morphological markers. In the absence of a fate map repair system, one would predict that these initial changes would result in drastic changes in the shape and size of larval and adult structures. However, these embryos develop into relatively normal larvae and adults. This indicates that there is plasticity in Drosophila embryonic development along the anterior-posterior axis. Embryos laid by mothers with six copies of bcd have reduced viability, indicating a threshold for repairing anterior-posterior mispatterning. We show that cell death plays a major role in correcting expanded regions of the fate map. There is a concomitant decrease of cell death in compressed regions of the fate map. We also show that compression of the fate map does not appear to be repaired by the induction of new cell divisions. In addition, some tissues are more sensitive to fate map compression than others.
Animals↗
Free radicals, lipid peroxides and antioxidants in blood of patients with myotonic dystrophy.
We studied the levels of free radicals, lipid peroxides and antioxidants, as well as superoxide dismutase (SOD) activity in the blood of six patients with myotonic dystrophy (MyD) (mean age 52.8, SD 5.0 years) and seven controls (mean age 48.8, SD 6.3 years). Electron spin resonance was used to assess the free radicals by the spin-trapping method using 5,5-dimethyl-1-pyrroline-1-oxide. The levels of C centre radical (P < 0.05) and H radical (P < 0.05) in blood from the six MyD patients were significantly higher than those in the seven controls. The SOD activities in red blood cells and serum from the six MyD patients showed no significant difference from those in the seven controls. The serum lipid peroxide concentration was increased in five of the MyD patients and tended to increase further as the disease progressed. The serum vitamin E level was low in two patients and in the low normal range in three. Serum coenzyme Q10 was decreased in four patients. The serum selenium level was decreased in two patients and that of serum albumin was decreased in three. Therefore we conclude that increased levels of free radicals and lipid peroxides and decreased antioxidant levels play an important role in the pathogenesis of MyD.
Antioxidants↗
Evaluation of Tl-201 SPECT for monitoring the treatment of pulmonary and mediastinal tumors.
Tl-201 single photon emission computed tomography (SPECT) was performed in 88 patients with pulmonary or mediastinal tumors in order to evaluate its usefulness for the detection of disease and for the assessment of the effect of treatment. We also examined mediastinal and hilar lymph node metastasis from lung cancer. Tl-201 SPECT showed abnormal accumulation on delayed images in all lung cancer patients with tumor diameters more than 12 mm. In the 14 operated lung cancer patients, mediastinal and hilar lymph node metastases with diameters of more than 15 mm were imaged, but one with a diameter of 9 mm was missed. The retention index (RI) was 27.52 +/- 31.58 in malignant tumors and -13.67 +/- 8.15 in benign tumors (p < 0.05). The RI was significantly lower after treatment than before treatment. The interval until tumor recurrence or reactivation tended to be longer in patients who showed a significant decrease in the RI after therapy. These findings suggest the usefulness of the RI as an index of therapeutic efficacy.
Adenocarcinoma↗
Superoxide dismutase and free radicals in sporadic amyotrophic lateral sclerosis: relationship to clinical data.
We studied the relationships between the superoxide dismutase (SOD) activity, free radical (FR) levels and clinical data in patients with sporadic amyotrophic lateral sclerosis (SALS). The SOD activities and blood FR levels of 16 patients with SALS (mean age 58.6 +/- 10.2 years), 11 with other neurological disease, including myotonic dystrophy (ND, mean age 53.5 +/- 9.1 years), and 15 normal control subjects (mean age 56.2 +/- 7.3 years) were measured. The mean levels of FR in blood from the patients with SALS and ND and the SOD activities in red blood cells (RBC) from those with ND were significantly higher than the corresponding control values. There was a positive correlation between the SOD activities in RBC and blood hydroxyl radical levels in the patients with ND, but neither the patients with SALS nor the controls showed such a correlation. The SALS patients without pyramidal signs showed slow disease progression and their mean RBC SOD activity was significantly higher than the corresponding control value. We compared the FR levels and SOD activities of 8 patients who needed a respirator within 40 months after the onset of SALS (SALS40, mean age 58.7 +/- 9.4 years), 3 who needed a respirator over 100 months after the onset of SALS (SALS100, mean age 58.3 +/- 15.9 years) and the controls. The mean blood FR levels of the SALS40 and SALS100 patients were significantly higher than the corresponding control values. The mean SOD activity in RBC from the SALS100 group was significantly higher than the SALS40 and control group values. Therefore, we concluded that elevated blood FR levels do not induce RBC SOD in SALS patients and that the disease progressed more rapidly in SALS patients with low than high RBS SOD activities.
Aged↗
Cerebrospinal fluid corticotropin-releasing hormone in neurodegenerative diseases: reduction in spinocerebellar degeneration.
Levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) were examined in patients with spinocerebellar degeneration (SCD) including olivopontocerebellar atrophy (OPCA), dentatorubropallidoluysian atrophy (DRPLA) and Friedreich's ataxia, Parkinson's disease (PD) and senile dementia of the Alzheimer type (SDAT), and normal aged subjects. CRH concentrations in CSF were significantly reduced in SCD compared to SDAT, PD and CSF and normal aged subjects. It is likely that degeneration not only of the cerebral cortex and the limbic system but also of the subcortical structures such as the brainstem and the cerebellum alters levels of CRH in CSF. Together with the recent anatomical and physiological evidence, the results suggest pathophysiological relevance of CRH for the cerebellar symptoms in SCD.
Adult↗
Tc-99m sestamibi uptake by malignant lymphoma and slow washout.
Tc-99m sestamibi has been used to detect primary brain tumors, lung tumors, and breast cancers. The authors report a patient who had superior vena cava (SVC) syndrome and underwent Tc-99m sestamibi and Tl-201 SPECT to differentiate the tumor from thrombus in the mediastinum because of an abnormal mass lesion on a contrast enhanced CT scan. An abnormal area of increased Tc-99m sestamibi uptake in the supra azygos area was demonstrated on early and delayed SPECT imaging. The washout of tumor uptake was slow. The removed tumor was confirmed to be malignant lymphoma.
Aged↗