Crossed aphasia elicited by direct cortical stimulation.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M Oishi
Publications and source records attributed to M Oishi.
Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid.
For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
Animals↗
Prevention of abdominal aortic aneurysms by simultaneous inhibition of NFkappaB and ets using chimeric decoy oligonucleotides in a rabbit model.
Abdominal aortic aneurysm (AAA) is one of the major vascular diseases caused by atherosclerosis. Because treatment for AAA mainly consists of surgery to prevent deaths from AAA rupture and there is a conspicuous absence of alternative therapeutic strategies, the development of minimally invasive treatment is needed. To develop a novel therapeutic approach, we examined the simultaneous inhibition of the transcription factors NFkappaB and ets, which regulate inflammation and matrix degradation, in a rabbit AAA model. In this study, we employed chimeric decoy oligodeoxynucleotides (ODN), containing the consensus sequences of both the NFkappaB- and ets-binding sites, to inhibit both the transcription factors simultaneously. Using a delivery sheet, we examined the inhibitory effect of chimeric decoy ODN on aortic dilatation. Ultrasound and angiographic analysis demonstrated that treatment with chimeric decoy ODN significantly prevented the progression of elastase-induced aortic dilatation. The inhibitory effect of chimeric decoy ODN on aortic dilatation was also confirmed by histological studies. Treatment with chimeric decoy ODN reduced the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and markedly inhibited the proteolysis of elastin as compared to scrambled decoy ODN. Interestingly, treatment with chimeric decoy ODN also suppressed VCAM-1 and MCP-1 gene expression, leading to inhibition of macrophage infiltration in the adventitia and media. The present study in a rabbit model provides a novel strategy to treat AAA by the simultaneous inhibition of both NFkappaB and ets using chimeric decoy ODN. Further modification of chimeric decoy ODN would be useful to treat AAA as a decoy-based therapy.
Animals↗
Intratumoural expression of thymidylate synthase is an independent predictor of prognosis in patients with squamous cell carcinoma of the tongue: results from a retrospective study.
The aim of this study was to assess the importance of immunohistochemical thymidylate synthase (TS) expression level as a prognostic marker in tongue cancer patients. In 140 patients with primary squamous cell carcinoma (SCC) of the tongue, intratumoural TS expression was evaluated by immunohistochemistry. The level of TS expression was determined by a semiquantitative scoring system, ranging from 1+ to 3+ according to the ratio of TS-positive cells. Of 140 patients, 64 (45.7%), 49 (35.0%) and 27 (19.3%) were assessed as 1+, 2+ and 3+, respectively. Univariate analyses demonstrated that both disease-free survival (DFS) and overall survival (OS) were significantly lower in patients with a TS 3+ tumour than in those with a TS 1+/2+ tumour (DFS: P = 0.0082, OS: P = 0.0100). In a multivariate analysis using the Cox regression model, cervical lymph-node status and TS expression level were selected as independent factors for DFS and OS. Maintenance adjuvant chemotherapy by oral 5-fluorouracil (5-FU) significantly improved DFS and OS in patients with a TS 1+/2+ tumour (DFS: P = 0.0027, OS: P = 0.0398). These data suggest that the level of immunohistochemical TS expression is an independent prognosticator in patients with tongue SCC, and may be useful in the selection of patients who would benefit from oral 5-FU adjuvant chemotherapy.
Adult↗
Association between lifetime cadmium intake and cadmium concentration in individual urine.
Explore the source record for details and available documents.
Aged↗
Inhibition of ets, an essential transcription factor for angiogenesis, to prevent the development of abdominal aortic aneurysm in a rat model.
The pathophysiology of abdominal aortic aneurysms (AAA) is considered to be complicated. As matrix degradation contributes to the progression of AAA, the destruction and degradation of elastin fibers caused by an increase in matrix metalloproteinases (MMPs) plays a pivotal role in the development of AAA. Although ets, an essential transcription factor for angiogenesis, regulates MMPs, the role of ets in the development of AAA has not yet been clarified. Thus, we evaluated the role of ets in a rat AAA model using a decoy strategy. Transfection of ODN into AAA was performed by transient aortic perfusion of elastase and by wrapping the AAA in a delivery sheet containing decoy ODN. The inhibitory effect of ets decoy ODN on ets binding activity was confirmed by gel mobility shift assay. MMPs expression was decreased in the aorta transfected with ets decoy ODN as compared to scrambled decoy ODN. Also, ultrasound study demonstrated that elastase-induced aneurismal dilation was significantly suppressed by transfection of ets decoy ODN at 4 weeks after treatment as compared to scrambled decoy ODN. Moreover, the destruction of elastin fibers was inhibited in the aorta transfected with ets decoy ODN, accompanied by a reduction of MMPs expression. An inhibitory effect of decoy ODN on MMP expression was confirmed by ex vivo experiments showing that transfection of decoy ODN into an organ culture of human aorta resulted in significant inhibition of the secretion of both MMP-1 and MMP-9. Here, we demonstrated that ets may play a pivotal role in the progression of AAA through the activation of MMPs in a rat model. Ets might be a potential target to develop pharmacotherapy/gene therapy to treat AAA through the inhibition of MMPs.
Animals↗
Generation of a total of 6483 expressed sequence tags from 60 day-old bovine whole fetus and fetal placenta.
Expressed sequence tags (ESTs) generated based on characterization of clones isolated randomly from cDNA libraries are used to study gene expression profiles in specific tissues and to provide useful information for characterizing tissue physiology. In this study, two directionally cloned cDNA libraries were constructed from 60 day-old bovine whole fetus and fetal placenta. We have characterized 5357 and 1126 clones, and then identified 3464 and 795 unique sequences for the fetus and placenta cDNA libraries: 1851 and 504 showed homology to already identified genes, and 1613 and 291 showed no significant matches to any of the sequences in DNA databases, respectively. Further, we found 94 unique sequences overlapping in both the fetus and the placenta, leading to a catalog of 4165 genes expressed in 60 day-old fetus and placenta. The catalog is used to examine expression profile of genes in 60 day-old bovine fetus and placenta.
Animals↗
Functional posterior rhizotomy for severely disabled children with mixed type cerebral palsy.
The authors evaluated the impact of functional posterior rhizotomy (FPR) for children with severely disabled mixed type cerebral palsy (CP). Three quadriplegic children at the age of 3, 4, and 10 years underwent FPR. They were classified as mixed type CP based on the clinical presentation of marked spasticity with dystonic posture. Preoperative Ashworth score of the lower extremity was 3.5, 4.5, 4.8 respectively. Two children showed prominent opisthotonus and all showed severe subluxation of the hip joint. Advanced scoliosis was associated in two children. FPR was performed from L2 to S1 in one child, L2 to S2 in one and L2 to S1/S2 in one based on the result of pudendal mapping. Rootlet cutting rate ranged from 66 to 75%. Postoperatively, Ashworth score dropped to 1.4, 1.2, 1.3, respectively. Functional improvement of the upper extremity and urination were confirmed in two children. Hip subluxation was reduced in one child and remained stable in two. A one-year follow-up review confirmed no relapse of spasticity among them. FPR achieved highly satisfactory surgical effects in children with severe mixed type CP. Although long-term follow-up is mandatory since there was a report of relapsed spasticity after FPR in this particular population of CP, FPR could be a choice of surgery in severely disabled children with mixed type CP.
Cerebral Palsy↗
Magnetoencephalographic representation of the sensorimotor hand area in cases of intracerebral tumour.
OBJECTIVE: To assess the clinical value of magnetoencephalography (MEG) in localising the primary hand motor area and evaluating cortical distortion of the sensorimotor cortices in patients with intracerebral tumour. METHODS: 10 normal volunteers (controls) and 14 patients with an intracerebral tumour located around the central region were studied. Somatosensory evoked magnetic fields (SEFs) following median nerve stimulation, and movement related cerebral magnetic fields (MRCFs) following index finger extension, were measured in all subjects and analysed by the equivalent current dipole (ECD) method to ascertain the neuronal sources of the primary sensory and motor components (N20m and MF, respectively). These ECD locations were defined as the primary hand sensory and motor areas and the positional relations between these two functional areas in controls and patients were investigated. RESULTS: The standard range of ECD locations of MF to N20m was determined in controls. In 11 of the 14 patients, MRCFs could identify the primary motor hand area. ECD locations of MF were significantly closer to the N20m in the medial-lateral direction in patients than in controls. In patients with a tumour located below the sensorimotor hand area, relative ECD locations of MF to N20m moved anteriorly over the standard range determined in the control subjects. These MEG findings correlated well with radiological tumour locations. The mean estimated ECD strength of MF was significantly lower in patients than in controls. CONCLUSIONS: MRCF was useful in localising the primary motor hand area in patients with intracerebral tumour. The relative ECD locations of MF to N20m describe the anatomical distortion of the sensorimotor cortex.
Adult↗
Ictal magnetoencephalographic discharges from elementary visual hallucinations of status epilepticus.
PURPOSE: To report the rare opportunity to study ictal magnetoencephalography (MEG) in a 26 year old man with simple partial status epilepticus that presented as elementary visual hallucinations (EVHs) in the right upper visual field. METHODS: The patient described his EVHs as "snowing on TV," "flickering lights," and "rotating coloured balls" that continued for several days. MEG and simultaneous EEG were recorded twice: during an episode of EVHs (ictal recordings) and after EVHs were controlled by medications (interictal recordings). RESULTS: During EVHs, MEG showed continuous periodic epileptiform discharges over the left posterior superior temporal region, while simultaneous EEG showed rhythmic theta waves and sporadic spikes over the left temporal region. The MEG discharge consisted of a three phase spike complex. Equivalent current dipoles (ECDs), modelled from spike complexes, localised in the left superior temporal area. After drug treatment controlled the EVHs, interictal MEG and EEG showed rare spikes over the same left temporal region. The average ictal ECD moment (mean (SD)) (128.7 (32.8 nAm)) was significantly weaker than the average interictal ECD moment (233.0 (63.9) nAm) (p<0.05). CONCLUSIONS: The continuous, periodic, and clustered discharges seen on ictal MEG were the sources of EVH. The weaker ictal ECD sources were frequently not detected by scalp EEG, while the stronger interictal sources, presumably originating from an extensive interictal zone, were sufficiently large to be seen as EEG spikes.
Adult↗
Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy oligodeoxynucleotides in NC/Nga atopic mouse model.
Atopic dermatitis, a chronic inflammatory skin disease characterized by relapsing eczema and intense prurigo, requires effective and safe pharmacological therapy. In this study, we examined the efficacy of ointment containing NF-kB decoy oligodeoxynucleotides (ODN) on atopic dermatitis lesions in NC/Nga mice, which are characterized by the spontaneous onset of atopic dermatitis in conventional conditions. Topical administration of NF-kB decoy ODN twice a month resulted in a significant reduction in clinical skin condition score and marked improvement of histological findings. Reduction of the atopic skin condition by NF-kB decoy ODN was accompanied by a significant decrease in migration of mast cells into the dermis and an increase in apoptotic cells. Here, we demonstrated the successful treatment of atopic dermatitis with ointment containing NF-kB decoy ODN in a mouse model, promising new therapy for atopic dermatitis.
Administration, Cutaneous↗
Large-scale evaluation of imprinting status in the Prader-Willi syndrome region: an imprinted direct repeat cluster resembling small nucleolar RNA genes.
Loss of paternal gene expression at the imprinted domain on proximal human chromosome 15 causes Prader-Willi syndrome (PWS), a complex multiple-anomaly disorder involving variable mental retardation, hyperphasia leading to obesity and infantile hypotonia with failure to thrive. Although numerous paternally expressed transcripts have been identified that reside in the candidate region, the individual contributions to the development of PWS have not been firmly established. Recent studies of mouse models carrying a cytogenetic deletion suggest that paternal deficiency of the SNRPN-IPW interval is critical for perinatal lethality of potential relevance to PWS. Here we determined the allelic expression profiles of a total of 118 cDNA clones using monochromosomal hybrids retaining either a paternal or maternal human chromosome 15. Our results demonstrated a preponderance of unusual transcripts lacking protein-coding potential that were expressed exclusively from the paternal copy of the critical interval. This interval was also found to encompass a large direct repeat (DR) cluster displaying a potentially active chromatin conformation of paternal origin, as suggested by enhanced sensitivity to nuclease digestion. Database searches revealed an unexpected organization of tandemly repeated consensus elements, all of which possessed well-defined box C and D sequences characteristic of small nucleolar RNAs (snoRNAs). Southern blot analysis further demonstrated a considerable degree of phylogenetic conservation of the DR locus in the genomes of all mammalian species tested, but not in chicken, Xenopus and Drosophila. These findings imply a potential direct contribution of the DR locus, representing a cluster of multiple snoRNA genes, to certain phenotypic features of PWS.
Base Sequence↗
Neurohypophyseal germinoma traced from its earliest stage via magnetic resonance imaging: case report.
BACKGROUND: We report a case in which magnetic resonance imaging (MRI) documented the formation of a neurohypophyseal germinoma from its earliest stage. CASE DESCRIPTION: A 9-year-old girl presented with polyuria, polydipsia, and growth retardation. Urinary and endocrinological examination indicated diabetes insipidus (DI) and growth hormone deficiency. No clear evidence of a mass in the hypothalamo-pituitary area was apparent on the first MRI scan. Follow-up MRIs and endocrinological examinations revealed that a tumor, arising from the stalk and posterior lobe of the pituitary gland, formed a mass and caused anterior pituitary function to deteriorate. Histologic diagnosis was germinoma based on open biopsy. CONCLUSION: Radiologic findings in this case indicated the primary site of this intrasellar germinoma to be the hypothalamo-neurohypophyseal region, designating this a "neurohypophyseal germinoma."
Child↗
Correlations between P300 components and regional cerebral blood flows.
To evaluate the diagnostic importance of event-related potential P300, the correlation between P300 and regional cerebral blood flow (rCBF) was investigated in various brain regions in patients with multiple cerebral infarction (16 cases), chronic alcoholism (11 cases) and Alzheimer's disease (5 cases) and in seven healthy people. Cognitive function was also evaluated by mini-mental state examination. P300 latency and rCBF was measured by recording of evoked potentials using an oddball paradigm and stable xenon computed tomographic scanning, respectively. A significant (P<0.05) negative correlation between P300 and rCBF was observed in the thalamus in patients with multiple cerebral infarction and chronic alcoholism. In addition, a significant (P<0.01) negative correlation between P300 latency and the mini-mental state examination score and positive correlation between rCBF in the thalamus and the mini-mental state examination score were observed. These findings suggest that P300 latency is associated with rCBF in the thalamus and cognitive function.
Aged↗
The influence of the laryngeal mask airway on the shape of the submandibular gland.
UNLABELLED: Although transient sialadenopathy of the submandibular gland associated with insertion of the laryngeal mask airway (LMA) has been described, the influence of the LMA on the submandibular gland is unknown. We measured the width and length of the submandibular glands by using ultrasonography in patients in whom the LMA was used. An increased intracuff pressure of the LMA, up to 150 cm H2O, was used in a prospective study of adult patients scheduled for elective surgery. The width of the gland increased with an increasing intracuff pressure from 50 to 100 cm H2O (P < 0.01) and 100 to 150 cm H2O (P < 0.01) but did not change from 0 to 50 cm H2O. There was no change in the length of the gland. We conclude that the submandibular gland was deformed by the insertion of the LMA. IMPLICATIONS: The findings in our study show that the submandibular triangle can be easily compressed by the insertion of the laryngeal mask airway (LMA). When inserting the LMA, it is important to consider that the LMA cuff may alter these tissues, which are situated between the lingual root and the submandibular triangle.
Adult↗
Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis.
Immune and inflammatory systems are controlled by multiple cytokines, including ILs and INFs. These cytokines exert their biological functions through Janus tyrosine kinases and STAT transcription factors. One such cytokine, IL-6, has been proposed to contribute to the development of rheumatoid arthritis (RA). We found that STAT3 was strongly tyrosine phosphorylated in synovial tissue of RA patients, but not those with osteoarthritis. Blockade of the IL-6-gp130-JAK-STAT3-signaling pathway might therefore be beneficial in the treatment of RA. We show here that the mRNA for the endogenous cytokine signaling repressor CIS3/SOCS3 is abundantly expressed in RA patients. To determine whether CIS3 is effective in treating experimental arthritis, a recombinant adenovirus carrying the CIS3 cDNA was injected periarticularly into the ankle joints of mice with antigen-induced arthritis or collagen-induced arthritis (CIA). Periarticular injection of CIS3 adenovirus drastically reduced the severity of arthritis and joint swelling compared with control groups. CIS3 was more effective than a dominant-negative form of STAT3 in the CIA model. Thus, induction of CIS3 could represent a new approach for effective treatment of RA.
Animals↗
Clinical factors of recurrent chronic subdural hematoma.
The clinical, radiological, and operative factors of recurrent chronic subdural hematoma (CSDH) were retrospectively analyzed in 116 patients with CSDH in 134 hemispheres, treated by one burr hole surgery. The correlation of recurrence was evaluated with personal and clinical factors such as age, sex, history of head injury, and interval from onset of initial symptoms to hospitalization; laboratory findings such as bleeding tendency and liver function; computed tomography (CT) findings such as hematoma density and brain atrophy; and operative findings such as additional procedures and postoperative residual air. The recurrence group (RG) included 10 hemispheres (7.5%) in 10 patients (8.6%). The interval from onset of symptoms to hospitalization was significantly shorter in the RG than in the nonrecurrence group (NRG). Headache was more frequently seen in the RG than in the NRG. Density of hematoma on CT was classified into five types: Low, iso, and high density, niveau, and mixed, and the incidence of recurrence was 0%, 2.3%, 17.2%, 12.5%, and 6.5%, respectively. Larger amounts of residual air in the postoperative hematoma cavity were associated with recurrence of CSDH. CSDH that progresses rapidly in the acute stage and appears as high density on preoperative CT is associated with a high incidence of recurrence. Intraoperative air invasion to the hematoma cavity should be avoided to prevent recurrence.
Aged↗
Angiotensin-converting enzyme inhibitors and probucol suppress the time-dependent increase in urinary Type IV collagen excretion of Type II diabetes mellitus patients with early diabetic nephropathy.
BACKGROUND: A multicenter prospective clinical trial was carried out in 9 National Hospitals in Japan to elucidate the time-dependent change in urinary Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or probucol is effective in preventing progression of renal involvement of diabetics by evaluating urinary Type IV collagen excretion. METHODS: Normo- and microalbuminuric patients with Type II DM were recruited. Patients were assigned to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV collagen excretion rate was also measured. RESULTS: Although, AER, urinary N-acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the control group did not vary over 24 months, urinary Type IV collagen excretion rate in the control group increased time-dependently (p < 0.01 vs baseline at 18 months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups, time-dependent increases in urinary Type IV collagen excretion rates were not observed. In the ACE-I group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 24 months (p < 0.05). In the probucol group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 6 months (p < 0.05). In the ACE-I group, AER decreased significantly compared with baseline at 18 months (p < 0.05) and at 24 months (p < 0.005). CONCLUSIONS: ACE-I has a beneficial effect and probucol may have a beneficial effect in preventing the progression of early diabetic nephropathy. Measurement of the urinary Type IV collagen excretion rate in combination with AER would be useful for the management of early renal involvement in Type II DM.
Acetylglucosaminidase↗