Biomedical subjects

T Ohashi

Publications and source records attributed to T Ohashi.

At least 37 records · Page 2Linked to original sources

PubMed2001

In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG.

Myelin oligodendrocyte glycoprotein (MOG) has attracted considerable attention due to its possible role in multiple sclerosis (MS). Previous studies have shown that MOG-reactive T cells are more commonly detected in MS patients than controls. In this report, we studied human MOG-reactive T cell clones generated from healthy individuals as well as MS patients. Our results indicate that immunoaffinity-purified MOG, which was routinely used in prior studies, is contaminated by anti-MOG antibody (mouse IgG), despite the inability to detect IgG by Western blotting. Here, we used continuous SDS-PAGE, which enabled us to isolate highly purified MOG devoid of contaminating mouse IgG.

Animals↗

PubMed2001

Role of the liver in regulating numbers of circulating neutrophils.

Neutrophils (polymorphonuclear leukocytes [PMNs]) carry potent destructive enzymes that can destroy invasive bacteria or damage normal tissue. PMNs have a half-life of only 6 hours in the blood, but the details of this homeostasis are unknown. In a rat model of endotoxemia, P-selectin was selectively up-regulated in hepatic sinusoids and veins where it was necessary for phagocytosis of PMNs by Kupffer cells in the liver, as opposed to the spleen or the lungs. Apoptotic PMNs appeared in the lungs and spleen only after inactivation of Kupffer cells by gadolinium chloride (GdCl(3)). Blocking of Fas protein reduced the number of apoptotic cells in the liver; binding of annexin V to phosphatidylserine (PS) reduced the number of PMNs phagocytosed by Kupffer cells. The results support a clearance pathway in which apoptosis and phagocytosis are effected by Kupffer cells after P-selectin-mediated sequestration. (Blood. 2001;98:1226-1230)

Animals↗

PubMed2001

Genetically modified bone marrow continuously supplies anti-inflammatory cells and suppresses renal injury in mouse Goodpasture syndrome.

In chronic inflammation, macrophages and neutrophils, which are derived from bone marrow, play a pivotal role. Therefore, reconstitution of bone marrow with anti-inflammatory stem cells may modify inflammation. In this study, transplantation-based gene therapy was applied to glomerular inflammation for a long-lasting suppression of the glomerular damage seen in chronic nephritis. Bone marrow cells were harvested from male donor mice, which had received 5-fluorouracil 3 days previously, and transduced with an interleukin 1 (IL-1) receptor antagonist (IL-1Ra) or a mock gene using a retrovirus vector. After confirmation that transduced cells possessed the transgene at approximately 0.7 copies per cell and secreted recombinant IL-1Ra, these cells were infused into sublethally irradiated (6 Gy) female recipients once daily for 4 consecutive days. These female recipient mice had the male Y antigen in bone marrow, liver, and spleen, and 10% to 20% of their spleen cells possessed the transgene even 8 weeks after transplantation. Glomerulonephritis was then induced in these mice. Renal function and histology were retarded in the mice whose bone marrow was reconstituted with IL-1Ra-producing cells compared with mock transduced cells. In situ hybridization using a Y painting probe revealed that transplanted donor cells were recruited into the glomerulus upon induction of nephritis, suggesting therapeutic effects were channeled through the secretion of IL-1Ra from these cells. Furthermore, the survival rate after a second challenge with nephrotoxic antibody was significantly improved in the IL-1Ra chimera. These results suggest that reconstitution of bone marrow for continuous supply of anti-inflammatory cells may be a useful strategy for the treatment of chronic inflammation.

Animals↗

PubMed2001

Low density lipoprotein receptor mRNA in rat liver is affected by resistant starch of beans.

The effects of resistant starches of beans on serum cholesterol and hepatic low density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 150 g/kg corn starch (CS), 150 g/kg adzuki (Vigna angularis) starch (AS), 150 g/kg kintoki (Phaseolus vulgaris, variety) starch (KS), or 150 g/kg tebou (P. vulgaris, variety) starch (TS) for 4 wk. There were no significant differences in body weight among groups through the experimental period. The liver weight in the CS group was 1.1-1.2 times higher than that in the AS, KS, and TS groups. The cecum weight in the TS was 1.4 times higher than that in the CS group, and the cecal pH in the CS group was significantly higher than in the other groups. The serum total cholesterol, very low density lipoprotein + intermediate density lipoprotein + LDL-cholesterol and high density lipoprotein (HDL)-cholesterol concentrations in the bean starch groups were significantly lower than those in the CS group through the feeding period. The total cholesterol/HDL-cholesterol ratio in the bean starch groups was also significantly lower than that in the CS group at the end of the 4-wk feeding period. The hepatic cholesterol concentration in the TS group was significantly higher than in the CS group at the end of the 4-wk feeding period. The relative quantity of hepatic apo B mRNA in the AS group was 1.2 times higher than that in the CS group, and the hepatic LDL receptor mRNA levels in the AS and TS groups were 1.8-2.0 times higher than that in the CS group. The results of this study demonstrate that AS, KS, and TS lowered the serum total cholesterol level by enhancing the hepatic LDL receptor mRNA level.

Animals↗

PubMed2001

Electrocochleogram after transection of vestibulo-cochlear nerve in a patient with a large acoustic neurinoma.

This study reports pre- and post-operative compound action potentials (CAPs) that were recorded from a 27-year-old woman with an acoustic neurinoma. During surgery it was necessary to totally sever her vestibulo-cochlear nerve to excise a large tumor. A pure tone audiogram changed to the scale-out pattern immediately after operation. However, CAP, the waveform of which was broadened, has been recorded 3 years post-operatively with a threshold elevation of 10 dB over the pre-operative threshold. This phenomenon suggests that CAP may originate from the extreme periphery of the auditory nerve within the cochlea. The broadening of the CAP was assumed to result from enhancement of the negative summating potential included in the CAP. We studied the effect of preceding stimulus on CAP using paired click stimuli pre- and post-operatively. A reduction of CAP amplitude in response to the second click of paired clicks was markedly suppressed in the inter-click interval between 3 and 80 ms post-operatively. We speculate that depletion of adaptation induced the abnormal CAP recovery described above and that the lateral efferent nerve system was involved in abnormal CAP adaptation with transection of the vestibulo-cochlear nerve in this case.

Action Potentials↗

PubMed2001

Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters.

Gene therapy for cancer requires efficient, selective gene transfer to cancer cells. In gene therapy for hepatocellular carcinoma (HCC), gene transfer is efficient for small tumors, but not for large tumors. The delivery of anticancer agents and of iodized oil esters as embolic agents through tumor-feeding arteries is known as transarterial embolization. We speculate that genes may be efficiently and selectively transferred for HCC using iodized oil esters because these esters may remain together with a genetic vector within HCC selectively. Hence, we have studied the effect of iodized oil esters on adenovirus vector-mediated gene transfer for HCC in vivo. A rat model of HCC induced with diethylnitrosamine and phenobarbital was injected with either AxCALacZ, which expresses the beta-galactosidase of Escherichia coli, or AxCALacZ and iodized oil esters into the hepatic artery. Histological comparisons revealed that the beta-galactosidase expression in the rats with HCC injected with AxCALacZ and iodized oil esters was greater (P<.0001) in small tumors (P=.0046) and large tumors (P=.0023), and more selective (P=.0229) than in only AxCALacZ-injected rats. These results suggest that iodized oil esters are injected into hepatic artery together with adenovirus vector, and that genes may be efficiently and cancer-selectively transferred to HCC.

Adenoviridae↗

PubMed2001

Intraventricular administration of recombinant adenovirus to neonatal twitcher mouse leads to clinicopathological improvements.

Twitcher mouse is a murine model of human globoid cell leukodystrophy (Krabbe disease), which is characterized by a genetic deficiency in galactocerebrosidase (GALC) activity. The nervous system is affected early and severely by demyelination in the white matter. So far, there is no effective treatment for Krabbe disease except bone marrow transplantation (BMT). However, BMT has inherent limitations such as unavailability of donors and graft-versus-host disease. In this study, we injected recombinant adenovirus encoding GALC into the lateral ventricle of twitcher mice at postnatal day 0 (PND 0) and the therapeutic effects were evaluated. Our results showed slight, but significant improvements in motor functions, body weight and twitching and a prolonged life span. In brain, GALC activity was increased to 15% that of normal littermates and psychosine concentration was decreased to 55% that of untreated twitcher mice at PND 15. The number of PAS-positive globoid cells in brain stem was also reduced significantly at PND 35. In contrast, when adenoviruses were injected to the twitcher mice at PND 15, almost no improvements were observed. These results demonstrate that the timing of treatment may be of great importance in Krabbe disease.

Adenoviridae↗

PubMed2001

Treatment of androgen-independent prostate cancer with dexamethasone: a prospective study in stage D2 patients.

PURPOSE: In order to evaluate the efficacy of dexamethasone in the treatment of Japanese men with androgen-independent prostate cancer, a prospective study was conducted using prostate-specific antigen (PSA) as a primary end-point. METHODS: Nineteen Japanese men with stage D2 androgen-independent prostate cancer were registered and treatment was started. After ruling out anti-androgen withdrawal syndrome, they were treated with dexamethasone (1.5 mg daily). Patients were monitored for PSA, symptoms, radiologic response, survival rate, time to disease progression, time to treatment failure and complications. RESULTS: Prostate-specific antigen levels decreased in nine patients (50.0%); five (27.8%) showed a 50% or greater decrease and two (11.1%) showed an 80% or greater decrease. For the nine patients, the mean duration of PSA response was 7.3 months and the median duration was 2.1 months (range, 1.2-27.5+). Bone pain, which was noted in 13 patients at study entry, improved in seven patients (53.8%). Of nine patients who had serial radiographic examinations with bone scan, three (33%) showed partial response, two (22%) were stable and four (44%) showed disease progression. Treatment was well tolerated, except for one patient who suffered a severe pulmonary infection. CONCLUSION: Dexamethasone decreased PSA levels and produced subjective symptomatic improvement in the patients with stage D2 androgen-independent prostate cancer.

Aged↗

PubMed2001

Poor outcome of 44 cemented total hip arthroplasties with alumina ceramic heads: clinical evaluation and retrieval analysis after 10-16 years.

We evaluated the long-term results of cemented total hip arthroplasty with alumina ceramic heads in 39 patients (44 hips) from 1981 to 1985. The study comprised 8 men (8 hips) and 31 women (36 hips). Their mean age was 54 (37-76) years and mean weight 52 (34-93) kg. The preoperative diagnoses were osteoarthrosis in 34 patients (38 hips), rheumatoid arthritis in 3 (4 hips) and idiopathic osteonecrosis of the femoral head in 2 (2 hips). The mean duration of follow-up was 13 (10-16) years. At this time, 6 cases had been revised because of aseptic loosening (5 hips showed loosening of both components and 1 acetabular loosening alone). Kaplan-Meier survivorship analysis with radiographic loosening as end-point showed 10-year survival rates of 75% for the acetabular component and 86% for the femoral. The mean linear wear rate of polyethylene was 0.10 mm/year radiographically--i.e., about the same as reported for many metal to polyethylene bearings. 5 alumina ceramic heads were retrieved and showed excellent surface roughness and roundness without scratches. However, debris stuck to the gaps was detected. The debris may act as third-bodies and affect polyethylene wear.

Adult↗

PubMed2001

Variance of vestibular-evoked myogenic potentials.

OBJECTIVES/HYPOTHESIS: Vestibular-evoked myogenic potential (VEMP) has been thought to originate from sacculus. The variance of this potential and the effectiveness of the adjustments of pInII amplitudes using average muscle tonus of ipsilateral sternocleidomastoid muscle were evaluated. In addition, clinical application of VEMP was examined in patients with acoustic tumors (ATs) and vestibular neurolabyrinthitis (VNL). STUDY DESIGN: Prospective evaluation of the VEMP in 18 normal volunteers and 6 patients. METHODS: Variance and left-right difference of each parameter, including pI latency, nII latency, pInII amplitude, and threshold, was analyzed. Input-output function of pInII amplitude was evaluated. Average muscle tonus was calculated in 20 ears and applied for adjustment of pInII amplitude. Sensitivity of each parameter of VEMP was examined in 3 patients with ATs and 3 patients with VNL. RESULTS: VEMP was present in all 36 ears of 18 control subjects. Thresholds of VEMP for normal subjects were 80 to 95 dB normal hearing level (nHL). The muscle tonus affected pInII amplitude significantly; however, no statistically significant improvement was observed in test-retest investigation after adjustment using muscle tonus. The threshold of the affected side was elevated compared with the non-affected side in all patients with ATs, whereas 2 of 3 patients showed normal pInII-ratio. One patient with VNL presented normal VEMP, whereas 2 patients presented no VEMP to the highest stimulus intensity. CONCLUSIONS: Interaural difference of thresholds might be the most useful parameters. Adjustment using average muscle tonus is not necessary when the subject is able to get sufficient muscle tonus.

Acoustic Stimulation↗

PubMed2001

Sound-evoked myogenic potentials and responses with 3-ms latency in auditory brainstem response.

OBJECTIVES: The vestibular-evoked myogenic potential (VEMP) has shed new light on vestibular testing. A large negative deflection with a 3-ms latency within the auditory brainstem response (ABR) has been reported in some patients with deafness. This negative deflection has been termed the N3 potential and it is assumed to be a vestibular-evoked potential. This study investigated the relationship between the VEMP and the N3 potential. STUDY DESIGN: Prospective evaluation of the VEMP and the N3 potential in 21 patients. METHODS: The oto-neurological tests, including caloric test, hearing sensitivity test, VEMP, and ABR, were performed and data were analyzed. RESULTS: The average hearing threshold ranged from 65 to above 110 dB, which includes 9 (37.5%) totally deaf ears. The N3 potentials were recorded in 10 (41.7%) ears. A normal VEMP was detected in 16 (66.7%) ears. Canal paresis was observed in 11 (45.8%) ears. CONCLUSIONS: Both the VEMP and the N3 potential appear to originate from the sacculus, but because the characteristics of these two responses are not identical, additional factors might be involved in the generation of the N3 potential.

Acoustic Stimulation↗

PubMed2001

Application of scanning acoustic microscopy for assessing stress distribution in atherosclerotic plaque.

Scanning acoustic microscopy (SAM) was equipped to assess the acoustic properties of normal and atherosclerotic coronary arteries. The SAM image in the atherosclerotic lesion clearly demonstrated that the sound speed was higher than that in the normal intima, and that the variation of elasticity was found within the fibrous cap of the plaque. Young's elastic modulus of each region was calculated and the finite element analysis was applied to derive the stress distribution in these arterial walls. In a case of normal coronary artery, the stress was dominant in the intima and the distribution was rather homogeneous and in a case of atherosclerosis, high stress was concentrated to the relatively soft lesion in the fibrous cap overlying lipid pool. SAM provides information on the physical properties, which cannot be obtained by the optical microscope. The results would help in understanding the pathological features of atherosclerosis.

Acoustics↗

PubMed2001

Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats.

The effects of mushroom fibers on serum cholesterol and hepatic low-density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 50 g/kg cellulose powder (CP), 50 g/kg maitake (Grifola frondosa) fiber (MAF), 50 g/kg shiitake (Lentinus edodes) fiber (SF), or 50 g/kg enokitake (Flammulina velutipes) fiber (EF) for 4 weeks. There were no significant differences in the body weight, food intake, liver weight, cecum weight, and cecum pH among the groups. Cecal acetic acid, butyric acid, and total short-chain fatty acid (SCFA) concentrations in the SF and EF groups were significantly higher than those in the other groups. The serum total cholesterol concentration in the CP group was significantly higher than that in the MAF and EF groups. The very LDL (VLDL) + intermediate-density lipoprotein (IDL) + LDL-cholesterol concentration in the CP group was significantly higher than that in the MAF, SF, and EF groups, whereas the high-density lipoprotein (HDL)-cholesterol concentration in the EF group was significantly lower than that in the other groups at the end of the 4-week feeding period. The hepatic LDL receptor mRNA level in the EF group was significantly higher than that in the CP group. The fecal cholesterol excretion in the MAF, SF, and EF groups was significantly higher than that in the CP group. The results of this study demonstrate that MAF and EF lowered the serum total cholesterol level by enhancement of fecal cholesterol excretion, and in particular, by enhancement of hepatic LDL receptor mRNA in EF group.

Acetic Acid↗

PubMed2001

Enzymatically enantioselective hydrolysis of prochiral 1,3-diacyloxyglycerol derivatives.

An enzymatically enantioselective ester hydrolysis of prochiral 1,3-diacyloxy-2-substituted-2-propanol to chiral 1-acyloxy-2,3-propanediol was studied. The (R)-monoester was prepared by selection of a suitable lipase and alkyl chain length of the substrate diester. Lipase D from Rhizopus delemer gave (R)-1-isobutyryloxy-2-(2,4-difluorophenyl)-2,3-propanediol with 97%ee and 87% yield at 15 degrees C and pH 5.5. The (R)-monoester is a key intermediate of azole antifungal agents.

Biochemistry↗

PubMed2001

Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.

We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study.

Adolescent↗

PubMed2001

Transplantation-based gene therapy for inflammatory diseases: focus on glomerulonephritis.

Over the past decade, bone marrow transplantation has come to be considered an ideal therapeutic strategy for the treatment of certain diseases affecting the hematopoietic system such as hemophilia, and several clinical trials have been performed. Although traditionally used for the treatment of lethal diseases, it is speculated that this approach could also be used in the treatment of non-lethal but much more common diseases, which are resistant to conventional therapies, and affect a large number of patients physically and even financially. Inflammation may be one target for transplantation-based gene therapy, since macrophages and neutrophils, which are basically derived from hematopoietic stem cells, have been identified as key determinants in the development of diseases. This article focuses on the glomerulonephritis as a model of local inflammation and reviews recent investigations on transplantation-based gene therapy for inflammatory diseases.

Bone Marrow Cells↗

PubMed2001

Comparison of spinal cord gray matter and white matter softness: measurement by pipette aspiration method.

OBJECT: Although the gray matter of the spinal cord has been thought to be softer than the white matter, there is no evidence to support this belief. Because the spinal cord is extremely soft, it has been difficult to measure the mechanical properties of the gray and white matter. The modulis of elasticity of the gray and white matter were measured in situ by using a pipette aspiration method. METHOD: The spinal cord specimens were excised from Japanese white rabbits. Specimens were cut to display the surfaces of axial, frontal, and sagittal sections. The surfaces of the gray and white matter were aspirated using a 0.8-mm-inner-diameter glass pipette while monitoring with a video microscope, and the deformed length in the pipette was measured on a monitor. In each case the modulus of elasticity was calculated by comparing the relationship between the aspiration pressure and aspirated volume of the specimen with that determined by finite element analysis. The moduli of elasticity of the gray and white matter were 3.4+/-1.4 kPa (mean +/- standard deviation) and 3.4+/-0.9 kPa in the axial section, 3+/-0.3 kPa and 3.5+/-0.5 kPa in the frontal section, and 3.5+/-0.9 kPa and 2.8+/-0.4 kPa in the sagittal section, respectively. CONCLUSIONS: No significant difference in modulus of elasticity was shown between the gray and white matter of the spinal in sections made in various directions.

Animals↗

PubMed2001

[Recovery from adaptation in human compound action potential following forward masking].

Recovery from adaptation was studied as changes in compound action potential (CAP) in response to clicks after broadband noise masking in volunteers with normal hearing. CAP was transtympanically elicited from the promontory using a needle electrode. Preceding masking noise and subsequent click stimuli were delivered separately from 2 loud speakers 80 cm from the tested ear. We evaluated the effect of masking noise duration and intensity on CAP recovery from adaptation as a function of delta t, defined as the interval between masking noise offset and click stimulus onset. Results were as follows: At delta t shorter than 200 ms or less, recovery from latency prolongation and amplitude decrease slowed with increasing masking noise duration and intensity. At delta t longer than 200 ms, no significant difference was seen in CAP recovery based on changes in masking noise duration or intensity. Recovery from adaptation, which depended on click intensity, took about 700 ms at a 40 dBnHL click and about 300 ms at a 60 dBnHL click. The influence of the middle ear muscle reflex on CAP recovery patterns is neglected when considering the intensity both masking noise and click stimulus. In CAP recovery, accumulated effects of the relative auditory-nerve refractory period may adversely affect recovery at very short delta t, while recovery from short-term adaptation, assumed involved in cochlear-hair cell synapse function, may be an important factor at delta t longer than 30-40 ms. Based on animal experiments showing different recovery times dependent on different auditory nerve spontaneous rates(SR), we concluded that at delta t of 200 ms or less, CAP recovery reflects high SR neuron activity, while at delta t longer than 200 ms, it mainly reflects that of low SR neurons.

Acoustic Stimulation↗