Biomedical subjects

Y Okubo

Publications and source records attributed to Y Okubo.

At least 91 records · Page 5Linked to original sources

PubMed2000

Seizure frequency and bilateral temporal abnormalities: a proton magnetic resonance spectroscopy of temporal lobe epilepsy.

Proton magnetic resonance spectroscopy ((1)H-MRS) was performed in seven healthy volunteers and 17 patients with temporal lobe epilepsy (TLE) to clarify the correlation of the severity of epilepsy with bilateral temporal changes in N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine + phosphocreatine (Cr). Despite unilateral EEG focus, bilateral temporal reduction in NAA /(Cho + Cr) was revealed in patients with intractable seizures. The potential for seizure generation correlated with the NAA /(Cho + Cr) reduction not only on the ipsilateral side but also on the contralateral side. Proton MRS proved to be a useful measurement for obtaining important information about the neuronal changes as well as the lateralization of the epileptogenic focus in TLE patients.

Adult↗

PubMed2000

Bone induction by Escherichia coli -derived recombinant human bone morphogenetic protein-2 compared with Chinese hamster ovary cell-derived recombinant human bone morphogenetic protein-2.

Most recombinant human bone morphogenetic protein (rhBMP) is currently obtained from Chinese hamster ovary (CHO) cells. If rhBMP with more activity could be derived from Escherichia coli (E. coli), a large quantity of rhBMP could be produced at low cost. The bone-inducing ability of an E. coli -derived rhBMP-2 (ErhBMP-2) variant with an N-terminal sequence was examined and compared with CHO cell-derived rhBMP-2 (CrhBMP-2). Two, 10, or 50 microgram of ErhBMP-2 or CrhBMP-2 was mixed with 3mg of atelopeptide type I collagen as the carrier, and specimens were implanted into the calf muscle pouches of Wistar rats (n= 5 in each group). Three weeks later, new bone had formed in all the ErhBMP-2-implanted and CrhBMP-2-implanted muscles. Radiographic and histological examinations showed that the bone induced by ErhBMP-2 had a large hollow bone matrix with more fatty marrow than the bone induced by CrhBMP-2. Quantitative analysis indicated that the activity of ErhBMP-2 was similar to that of CrhBMP-2, so ErhBMP-2 may be useful for inducing bone formation.

Alkaline Phosphatase↗

PubMed2000

The effect of blood supply in muscle and an elevated muscle flap on endogenous tissue-engineered bone by rhBMP-2 in the rat.

Metabolism and remodeling of bony tissue are maintained and controlled by blood supply. In this study, bony tissue osteoinduced heterotopically by recombinant human bone morphogenetic protein-2 (rhBMP-2) in rat muscles with different amounts of blood supply was investigated. The implant beds were in the latissimus dorsi muscle (LDM) and in the space wrapped with an elevated latissimus dorsi muscle flap (LDMF). The blood flow was preestimated at two muscle sites using a laser Doppler blood flowmeter. The flow value of the LDM was 2.23 +/- 0.17 ml/min/100 g (mean +/- standard deviation). The flow values of the LDMF were 1.71 +/- 0.22 ml/min/100 g 30 minutes after elevating the LDMF, 1.75 +/- 0.20 ml/min/100 g after 1 week, 1.83 +/- 0.19 ml/min/100 g after 2 weeks, and 1.99 +/- 0.18 ml/min/100 g after 3 weeks. Bony tissues induced heterotopically by rhBMP-2 were examined radiographically and histologically. On radiographs, radiopaque shadows in the LDM were almost as large as those in the LDMF. The radiopacity in the LDM was a little higher than that of the LDMF. The microscopic findings showed increased trabeculae and more hematopoietic marrow in the LDM than lamellalike bone in the LDMF. Mean bony area in the implant was 1.05 +/- 0.26 mm2 in the LDM, and was 0.70 +/- 0.11 mm2 in the LDMF. Bony proportions in the overall implant area were 18.3 +/- 3.46% in the LDF and 12.1 +/- 2.18% in the LDMF. The current study indicates that blood supply is an important factor for promoting heterotopic osteoinduction by rhBMP-2 to produce massive bony tissue as an endogenous method of tissue engineering.

Animals↗

PubMed2000

Osteogenesis by recombinant human bone morphogenetic protein-2 at skeletal sites.

Osteogenesis was evaluated in the mandibular bone by combinations of various dosages of recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite (four groups: Group I, 2 micrograms recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite; Group II, 10 micrograms recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite; Group III, 50 micrograms recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite; Control Group, only atelopeptide Type I collagen and porous hydroxyapatite). The prepared materials were implanted in the mandibular bone hole (7 mm in diameter, 2 mm deep). Three weeks later, the alkaline phosphatase activity in the implanted region was determined, and the histologic features of the excised tissue were examined. There were significant differences in histologic and biochemical findings among the four groups. In the recombinant human bone morphogenetic protein-2 implanted groups, osteogenesis increased with the dosage of recombinant human bone morphogenetic protein-2, as assessed by alkaline phosphatase activity and histologic findings. The results suggest that atelopeptide Type I collagen is an effective carrier for recombinant human bone morphogenetic protein-2 and that porous hydroxyapatite would be advantageous for clinical application as a material to maintain its original form after implantation.

Alkaline Phosphatase↗

PubMed2000

Two cases of confluent and reticulate papillomatosis: successful treatments of one case with cefdinir and another with minocycline.

The present report presents two cases of confluent and reticulate papillomatosis. Case 1 was a 24-year-old man who had suffered from skin eruptions for six months, and Case 2 was a 19-year-old woman who had had this disease for three days. In both patients, reticular dark brown papules, accompanied by mild keratosis and infiltration, spread from the trunk to the neck and upper arm. Direct light microscopy did not detect the presence of any fungi, and histopathological examinations confirmed hyperkeratosis, acanthosis, papillomatosis, and mild small-round-cell infiltration. Thus, these patients were diagnosed as confluent and reticulate papillomatosis. Neither one had diabetes or thyroid dysfunction. In Case 1, cefdinir was effective, and in Case 2, minocycline hydrochloride and ketoconazole were effective. To the best of our knowledge, this was the first documented case of confluent and reticulate papillomatosis responding to cefdinir.

Adult↗

PubMed2000

A case of dermatomyositis associated with mechanic's hand.

A 67-year-old man was referred to the Department of Internal Medicine at Tokyo Medical University with interstitial pneumonia in July 1999. He presented with keratotic plaques on both palsm and on the ventral and lateral sides of his fingers. Erythematous keratosis was observed on the dosal aspect of his fingers and metatarsophalangeal (MP) joints. Edematous erythema was seen on the patient's chest, back, and the extensor surfaces of his arms. Electromyography revealed a myogenic pattern and an increased level of myogenic enzymes was found in the blood. Histological findings of the ventral sides of his fingers showed hyperkeratosis and parakeratosis of the dermal tissue and liquefaction degeneration of the basal layer at the papilla. Based on these findings, the patient was given a diagnosis of dermatomyositis associated with mechanic's hand. A systemic examination confirmed interstitial pneumonia and carcinoma of the duodenal papilla. Mechanic's hand is a type of dermatitis associated with myopathy first reported by Stahl et al. in patients with collagen disease. We report herein the first documented case of mechanic's hand in Asians.

Adenocarcinoma↗

PubMed2000

[Clinical study of infection associated hemophagocytic syndrome].

Hemophagocytic syndrome (HPS) causes pancytopenia, increased blood LDH level, liver dysfunction, DIC, etc. with macrophages appearing in the bone marrow, spleen, lymph nodes, etc. Adult HPS is mostly secondary to various infections, malignant tumors, etc. and sometimes has a serious outcome. Particularly infection associated HPS (IAHS) is triggered by viral, bacterial and fungal infections. The cases of unknown primary disease and suspected IAHS of unidentified pathogenic microorganism are often encountered in the clinical setting. The authors compared IAHS and malignant associated HPS (MAHS) and classified IAHS into viral associated HPS (VAHS), bacterial associated HPS (BAHS) and fungal types to compare the test values based on the test findings at the onset in the HPS cases treated at our Department. The patients consisted of 21 HPS cases, 11 IAHS cases (VAHS 4, BAHS 5, fungal 2) and 10 MAHS cases. Based on the test findings (WBC, Hb, Plt, LDH, ferritin, myelogram, cytokines, [IFN alpha, TNF gamma, IL-6, sIL-2R, M-CSF], adhesion molecules [sICAM-1, sVCAM-1, sELAM-1, sL-selectin]) at the onset, a comparison between IAHS and MAHS and among the IAHS cases classified by pathogenic microorganism was made. In the comparison between IAHS and MAHS, the Hb value was significantly decreased and sIL-2R tended to be increased at the onset in MAHS. When comparing the IAHS cases by pathogenic microorganism, Plt was significantly decreased and sICAM-1 and sVCAM-1 were increased at the onset in the BAHS, The BAHS cases had serious underlying diseases and poor prognosis with high incidence of DIC complications. We are going to accumulate more cases for early diagnosis and treatment of IAHS.

Adolescent↗

PubMed2000

Longitudinal follow-up study of smoking-induced lung density changes by high-resolution computed tomography.

To evaluate the ability of high-resolution computed tomography (HRCT) to detect longitudinal changes in structural abnormalities caused by smoking, HRCT and pulmonary function tests were used to examine nonsmokers, current smokers, and past smokers annually for 5 yr. Inspiratory HRCT was taken for the upper, middle, and lower lung fields, while expiratory images were obtained for the upper and lower lung fields only. We estimated the three quantitative CT parameters including MLD (mean CT value), HIST (CT value with the most frequent appearance), and %LAA (relative area of low attenuation with CT values less than -912 HU). Most of the pulmonary function tests, excepting FEV(1), did not change annually, whereas many of the inspiratory HRCT parameters did. In nonsmokers, only %LAA in the middle or lower lung fields exhibited an annual increase. In current smokers, %LAA in the upper lung field was augmented, while inspiratory MLD or HIST in the middle or lower lung field became more positive. In past smokers, %LAA in any lung field examined increased. The annual change in %LAA in the upper lung field was larger for past smokers than nonsmokers, with little difference between past and current smokers. Expiratory CT parameters showed few annual changes in all groups. In conclusion, (1) aging increases airspace abnormalities, mainly in the lower lung field; (2) although continuous smoking worsens airspace abnormalities mainly in the upper portion of the lung, this trend does not seem to slow down even after smoking cessation; and (3) inspiratory HRCT images are superior to expiratory images for longitudinal estimation of structural abnormalities caused by aging and smoking.

Aging↗

PubMed2000

Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.

Adrenergic alpha-Agonists↗

PubMed2000

The tyrosine kinase activity of the chicken insulin receptor is similar to that of the human insulin receptor.

The tyrosine kinase activity of a chimeric insulin receptor composed of the extracellular domain of the human insulin receptor (IR) and the intracellular domain of the chicken IR was compared with wild-type human IR. The degrees of autophosphorylation, phosphorylation of IRS-1, and in vitro phosphorylation of an exogenous substrate after stimulation by human insulin were similar to that seen with the human IR. We conclude that the insulin resistance of chickens is not attributable to a lower level of intrinsic tyrosine kinase activity of IR.

3T3 Cells↗

PubMed2000

Urinary excretions of albumin and type IV collagen in normotensive and hypertensive subjects.

Plasma albumin leaks into urine as a result of glomerular hypertension and basement membrane injury, while urinary type IV collagen derives from mesangial matrix and glomerular basement membrane. The purpose of this study was to elucidate the pathophysiological significance of these urinary microproteins as an indicator of cardiovascular organ injuries in hypertension. In health-checkup participants without diabetes, proteinuria, or microhematuria, and who were not being treated for hypertension or any other disease at the time of enrollment, urinary albumin and type IV collagen were measured and their relations to organ injuries and cardiovascular risk factors were evaluated. Of 1,079 subjects (40- to 65-year-old; 256 men and 823 women) enrolled in the study, 120 (11.1%) had untreated hypertension exceeding 140/90 mmHg. Urinary albumin was positively correlated with both age (r=0.16, p<0.001) and systolic blood pressure (r=0.27, p<0.001). Urinary type IV collagen was not only positively correlated with age (r=0.12, p<0.001) and diastolic blood pressure (r=0.14, p<0.001) but also negatively correlated with blood hemoglobin (r=-0.12, p<0.001). Urinary albumin, but not type IV collagen, had a significant relation to electrocardiographic signs of left ventricular hypertrophy (p=0.012) and retinal arteriosclerosis on fundoscopy (p <0.001). Thus both albumin and type IV collagen would seem to have increased in association with age and hypertension in this cohort. It is suggested that urinary albumin is an indicator not only of renal injury, but also possibly of development of cardiac hypertrophy and arteriosclerotic changes. Urinary type IV collagen, on the other hand, may be associated with renal tissue injuries that affect erythrokinetics.

Adult↗

PubMed2000

Osteoinduction by recombinant human bone morphogenetic protein-2 at intramuscular, intermuscular, subcutaneous and intrafatty sites.

To compare the osteoinductive activity of recombinant human bone morphogenetic protein-2 (rhBMP-2) at various sites in rats, 5 microg of rhBMP-2 were implanted into various sites, using atelopeptide type-I collagen (CL) as a carrier (BMP groups). CL implantation was used as a control. Forty Wistar rats were divided into intramuscular, intermuscular, subcutaneous and intrafatty site groups (IrM, IeM, SC and IF, respectively). Bone formation was evaluated radiographically, histologically and biochemically 21 days after implantation. In the BMP groups, the alkaline phosphatase activity and calcium content at all sites were higher than those in the control groups. Among the BMP groups, the new bone formation was highest in the IrM and lowest in the IF radiographically, histologically and biochemically. Five microg of rhBMP-2, a relatively low dose, induced adequate new bone formation in all sites. The variations of osteoinductive activity of rhBMP-2 in various sites may be due to differences in the blood supply.

Adipose Tissue↗

PubMed2000

[A case of intrathoracic schwannoma derived from the left vagus nerve].

We report a case of schwannoma asymptomatic for 9 years, derived from the left vagus nerve in the middle mediastinum. This spindle-shaped tumor caused paralysis of the left recurrent nerve as an initial clinical manifestation with cough. T2-weighted magnetic resonance imaging (MRI) showed a neurogenic tumor with a characteristic target appearance and with constituents of different intensities: mucinous material in the peripheral zone and solitary tissue in the central zone. But, this different intensity is not directly reflected by the histopathologic features of Antoni types A and B. These findings suggest that MRI is useful for determining the parent nerve of a neurogenic tumor and is helpful for the diagnosis.

Adult↗

PubMed1999

Beta-1 (10-20 Hz) cortical oscillations observed in the human medial temporal lobe.

During wakefulness, signals from subdural electrodes attached to the basal and medial temporal lobes of adult human epilepsy patients revealed a rhythmic oscillation in the beta-1 frequency range (10-20 Hz). This activity was more prominent in the medial than in the basal temporal cortex. We also observed simultaneous oscillations in alpha frequency activity in the medial and the basal temporal cortices. In an eyes-open condition, the alpha oscillation was attenuated, while the beta-1 oscillation in the medial temporal lobe was not. This is the first report that the beta-1 oscillation is present in the human medial temporal lobe. Since we recorded this activity from within the limbic system, beta-1 activity may be an analog of the hippocampal rhythmic slow activity observed in some animals.

Adult↗

PubMed1999

Expression of bone morphogenetic protein-2 via adenoviral vector in C2C12 myoblasts induces differentiation into the osteoblast lineage.

To examine the effectiveness of a gene transfer of bone morphogenetic protein (BMP)-2 into C2C12 myoblasts, we constructed a human BMP-2-expressing replication-deficient adenoviral vector, AxCAOBMP-2. C2C12 cells were infected in vitro with either this viral vector or an Escherichia coli LacZ gene-expressing control adenovirus vector. An efficient gene transfer to the C2C12 cells was confirmed with the LacZ gene-expressing vector by X-gal staining. Abundant BMP-2 expression in C2C12 cells infected with this viral vector was confirmed by immunofluorescence and Western blot analysis. C2C12 cells transferred with the BMP-2 gene by this vector produced alkaline phosphatase in the cells and also produced and secreted osteocalcin in the culture medium, demonstrating that a gene transfer of BMP-2 into C2C12 cells in vitro could convert these cells from myoblast to osteoblast lineage.

Adenoviridae↗

PubMed1999

Characterization of psychrophilic alanine racemase from Bacillus psychrosaccharolyticus.

A psychrophilic alanine racemase gene from Bacillus psychrosaccharolyticus was cloned and expressed in Escherichia coli SOLR with a plasmid pYOK3. The gene starting with the unusual initiation codon GTG showed higher preference for codons ending in A or T. The enzyme purified to homogeneity showed the high catalytic activity even at 0 degrees C and was extremely labile over 35 degrees C. The enzyme was found to have a markedly large Km value (5.0 microM) for the pyridoxal 5'-phosphate (PLP) cofactor in comparison with other reported alanine racemases, and was stabilized up to 50 degrees C in the presence of excess amounts of PLP. The low affinity of the enzyme for PLP may be related to the thermolability, and may be related to the high catalytic activity, initiated by the transaldimination reaction, at low temperature. The enzyme has a distinguishing hydrophilic region around the residue no. 150 in the deduced amino acid sequence (383 residues), whereas the corresponding regions of other Bacillus alanine racemases are hydrophobic. The position of the region in the three dimensional structure of C atoms of the enzyme was predicted to be in a surface loop surrounding the active site. The region may interact with solvent and reduce the compactness of the active site.

Alanine Racemase↗

PubMed1999

Molecular basis for Rh(null) syndrome: identification of three new missense mutations in the Rh50 glycoprotein gene.

Rh(null) is a rare autosomal recessive disorder characterized by an absence of Rh antigens and a varying degree of hemolytic anemia and spherostomatocytosis. We report studies of two Japanese Rh(null) cases and describe three new missense mutations of RHAG, the locus that encodes Rh50 glycoprotein and modulates Rh antigen expression. In Rh(null)(HT), RHAG harbored in exon 6 two G-->A transitions, GTT-->ATT and GGA-->AGA, which cause Val(270)-->Ile and Gly(280)-->Arg substitutions, respectively. These missense mutations were cotransmitted from the propositus to the children and were predicted to reside in endoloop 5 and transmembrane (TM) segment 9, respectively. In Rh(null)(WO), RHAG contained in exon 9 a single G-->T transversion, GGT-->GTT, which caused a Gly(380)-->Val missense change in TM12 segment. The G-->T transversion, which is located at the +1 position of exon 9, had also affected pre-mRNA splicing and caused partial exon skipping. Although both Rh(null) cases had a structurally normal RH antigen locus, hemagglutination and immunoblotting showed no expression of Rh antigens or proteins. These results correlate each mutation with a structural defect in the respective TM domain of Rh50 glycoprotein.

Amino Acid Sequence↗

PubMed1999

Mapping of central D2 dopamine receptors in man using [11C]raclopride: PET with anatomic standardization technique.

D2 dopamine receptors are of interest in the pathophysiology of schizophrenia. For group comparisons of neuroreceptor distribution measured by PET on a pixel-by-pixel basis, an anatomic standardization technique is required. The aim of the present study is to build a database of normal D2 dopamine receptor distribution using [11C]raclopride and an anatomic standardization technique. In each subject, two PET measurements were performed with rapid bolus injection and with continuous infusion of [11C]raclopride. The radioactivity of the PET images were integrated in the time interval. Integrated images were normalized by the radioactivity of the cerebellum, providing a measure of the binding potential (BP) in each pixel. Each PET image was transformed into a standard brain anatomy using a Computerized Brain Atlas system. From the standardized PET images, the sample mean and the SD of the BP were calculated in each pixel. On the anatomically standardized average images for the both rapid bolus injection and continuous infusion, high BP was observed in the putamen and the caudate nucleus, whereas low BP was observed in the cerebral cortices. The BP for the thalamus and the substantia nigra were slightly higher than those for the cerebral cortices. This regional distribution is in good agreement with the distribution of D2 dopamine receptors known from in vitro studies. The anatomic standardization technique permits to build a database of the normal D2 dopamine receptor distribution in the living human brain. This technique can be applied for group comparisons on a pixel-by-pixel basis.

Adult↗