Search PubMed⌕ Search

Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 649 records · Page 36Linked to original sources

Alteration of radiosensitivity of quiescent cell populations in solid tumors irradiated with X-rays twice at various intervals.

5-Bromo-2'-deoxyuridine (BUdR) was injected into SCC VII or EMT6/KU tumor-bearing mice intraperitoneally to label all the proliferating tumor cells. First, the mice were irradiated with X-rays at a dose of 10 Gy, followed by a dose of 0-20 Gy at 0, 12, 24 or 48 h later. During the interval, no BUdR was injected. Immediately after the second irradiation, the tumors were excised and trypsinized. The micronucleus (MN) frequency in cells without BUdR labeling was determined by means of incubation with cytochalasin-B (a cytokinesis-blocker) and immunofluorescence staining for BUdR. When the tumors were not pretreated with BUdR before the first irradiation, the MN frequency in all tumor cells was determined. To determine the labeling indices of SCC VII and EMT6/KU tumors at the time of the second irradiation, each group also included mice that were continuously administered BUdR until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the first irradiation. The MN frequency of all tumor cell populations obtained immediately after the second irradiation decreased in proportion to the increase in interval time. However, in both tumor systems, the MN frequency of unlabeled cell populations, which could be regarded as quiescent cells in the tumors at the time of the first irradiation, was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings support the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation.

Animals↗

Two phosphatase sites on the Ca2+ channel affecting different kinetic functions.

1. Changes in dihydropyridine-sensitive (L-type) Ca2+ channel kinetics were studied after prolongation of intrinsic phosphorylated time by the phosphatase inhibitor okadaic acid (OA) in cell-attached patches made from single isolated rabbit ventricular myocytes, using barium as the charge carrier. 2. At low concentrations (0.001-1 microM), OA decreased the number of sweeps without openings, while open duration was not changed. However, when cells were pretreated by a membrane-permeant cyclic AMP, 0.1 microM OA induced long-lasting channel openings as well. 3. At high concentrations (10-750 microM), OA additionally induced long-lasting openings, resulting in open time distributions that were best fitted by two exponentials. 4. The durations of an available state (TS) and an unavailable state (TF) were estimated by the numbers of non-blank sweeps per run and blank sweeps per run by applying repetitive 45 ms steps at 2 Hz to 0 mV from holding potentials of -80 mV. TS was well fitted by an exponential curve, of which the time constant was increased from 0.67 to 1.60 sweeps by 0.1 microM OA, while TF was 0.347 sweeps and remained unchanged. 5. OA activated brief openings and long-lasting, wide openings in a concentration-dependent manner. Namely, we find different dose-response relationships for the two kinetic effects of increased opening probability (mode 1) and prolongation of opening (mode 2). This behaviour suggests that there are at least two modulatory phosphorylation sites that are dephosphorylated by different phosphatases.

Animals↗

Unusual neuroradiological findings in systemic lupus erythematosus.

A 47-year-old woman affected by systemic lupus erythematosus (SLE) presented with headache, fever, splenomegaly and edema of the lower extremities. CT showed diffuse low density in the cerebral white matter and marked splenomegaly in the abdomen. T2-weighted MR images showed diffuse high intensity lesions in the white matter. After immunosuppressive therapy with prednisolone, there was marked improvement in the cranial CT and MR appearances. The underlying pathological process was probably edema secondary to a lupus microangiopathy. SLE can be complicated by a widespread abnormality of the white matter with marked radiological changes but few neurological signs. In the present case, only an episodic mild hemiparesis for 3 weeks without seizure and psychiatric disturbance was found neurologically during the whole clinical course.

Activities of Daily Living↗

A seroimmunological analysis of Down syndrome.

Down syndrome (DS) was studied in terms of immunological function and serological aspects. It was found that antibody levels against rubella and pertussis in the sera from 36 institutionalized DS patients were comparable with those of healthy controls while low antibody levels were detected against mumps and measles. Six tumor markers were also assayed in the serum from DS patients and the serum concentration of alpha-1-acid glycoprotein (alpha 1-AGP) and immunosuppressive acidic protein, an analogous glycoprotein of alpha 1-AGP, were significantly higher than those of the control group. Multivariate discriminant function was constructed based on the concentration of tumor markers. The function could discriminate between the two groups at a sensitivity of 92.3%. Flow-cytometrical analysis has revealed that helper T level of DS patients' sera was lower than that of the control group.

Adolescent↗

Mechanism of cAMP-dependent modulation of cardiac sodium channel current kinetics.

beta-Adrenergic modulation is one of the most important regulatory mechanisms of ion channel function. Only recently, however, have beta-adrenergic effects on cardiac Na+ channel activity been recognized, and some diversity of effects has been reported in different preparations. We report studies of protein kinase A-dependent phosphorylation effects on cardiac Na+ current using the macropatch on-cell mode voltage-clamp technique to maintain cytoplasmic composition intact. During the first 5 minutes after addition of 8-(4-chlorophenylthio)cAMP to the bath, the midpoints of both voltage-dependent availability and conductance shifted in the hyperpolarizing direction an average of -7.5 +/- 2.8 mV (n = 31). Moreover, these effects were not species specific; similar results were obtained in canine, rabbit, and guinea pig myocytes, and a similar shift occurred after exposure to 5 microM isoproterenol. Maximum conductance did not change, nor did single-channel conductance. The shifts of conductance and voltage-dependent availability that were induced by protein phosphorylation were distinct from and independent of the slow background shift in kinetics. We measured the background shift to be less than 0.3 mV/min and to be restricted to the channels within the patch. Pretreatment of cells with a blocker of protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H-89), prevented the effect of 8-(4-chlorophenylthio)cAMP while not affecting the background shift in kinetics. Although clearly not the result of addition of a negatively charged phosphate to the inside face of the channel, cAMP-dependent phosphorylation affects the voltage-dependent kinetics, as expected, by an electrostatic interaction with the voltage sensor.

Animals↗

Transforming growth factor-beta 1 stimulates chondrogenesis and inhibits osteogenesis in high density culture of periosteum-derived cells.

Chick periosteum-derived mesenchymal cells have been reported to exhibit both osteogenic and chondrogenic potentials in high cell density culture conditions. Using this culture system, the effects of transforming growth factor-beta (TGF beta) on proliferation and differentiation of periosteal mesenchymal cells were studied. Supplementation with TGF beta 1 at doses of 0.3-1.0 ng/ml shortened the time course of chondrogenesis and increased the amount of cartilage formed in the lower part of the culture. On the other hand, the amount of bone formed in the upper part of the culture decreased with TGF beta treatment, whereas the time course of osteogenesis remained unaffected.

Animals↗

The detection and modification of the hypoxic fraction in quiescent cell populations in murine solid tumours.

Mice bearing SCC VII or EMT6/KU tumours were irradiated after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumour cells, and the tumours were then excised and trypsinized. The tumour cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BUdR labelling was determined using immunofluorescence staining to BUdR. This MN frequency was then used to calculate the surviving fraction of unlabelled cells from the regression line for the relation between MN frequency and the surviving fraction of all tumour cells. Thus a cell survival curve could be determined for cells not labelled by BUdR, which can be regarded as quiescent tumour cells for all practical purposes. Assays performed immediately after irradiation of both normally aerated and hypoxic tumours showed that quiescent cells contained higher hypoxic fractions than the tumour cells as a whole. Furthermore, administration of nicotinamide before irradiation or the placement of mice in a circulating carbogen (95% O2, 5% CO2) chamber for 30 min before and during irradiation altered the acutely and chronically hypoxic fractions of the proliferating and quiescent tumour cell populations in a way which depended on the tumour system. Combined nicotinamide and carbogen therapy was shown to have a large potential to sensitize cells to low-dose radiation in vivo. In addition, this assay method appears to be useful for determining the size of the hypoxic fraction of quiescent tumour cells in murine solid tumours.

Animals↗

Malignant histiocytosis with multiple skin lesions in a dog.

A 7-year-old male Yorkshire terrier was examined for multiple plaques and nodules on the skin. The clinical, cytological and histopathological features indicated a malignant histiocytosis. Cytoreductive chemotherapy produced moderate clinical improvement, but died at day 90 after the first admission. Pathological examination revealed the neoplastic histiocytes in the skin as well as in the myocardium and skeletal muscles.

Animals↗

Placental and plasma cystine aminopeptidase in pregnant animals.

The placental and plasma cystine aminopeptidase (CAP) in pregnant animals was examined on stability after the treatment with L-methionine, ethylene diamine tetra-acetic acid (EDTA) and heat. Inhibitory effects of these treatments on enzyme activities were different among CAPs from the animal species, however, significant correlation in those effects between placental and plasma CAPs was observed. These results suggested that plasma CAP might reflect placental CAP and seemed to be available for estimating maternal gestational conditions.

Animals↗

Experimental implant-related osteomyelitis treated by antibiotic-calcium hydroxyapatite ceramic composites.

The efficacy of locally implanted antibiotic-calcium hydroxyapatite ceramic composites was investigated for the treatment of experimentally produced, implant-related osteomyelitis in rats. High concentrations of antibiotics were detected at the site of infection and bacteria were eradicated without removal of the metal implants. Parenteral antibiotics and surgical debridement, alone or in combination with antibiotic-impregnated acrylic bone cement, all failed to eradicate the infections.

Animals↗

Bone induction in monkeys by bone morphogenetic protein. A trans-filter technique.

We investigated bone induction by bone morphogenetic protein in primates, comparing it with that seen in rodents. Twelve Millipore diffusion chambers containing 5 mg of semipurified bone morphogenetic protein were implanted into the dorsal muscles of 12 young, adult crab-eating monkeys (Macaca fascicularis) and were retrieved six weeks later. In six of nine unbroken chambers, new bone with haematopoietic marrow had been induced on the host-side surface of the filter. The incidence of trans-filter bone induction in the monkeys was almost equal to that observed in mice, and the new bone yield was approximately half as much as in mice. Our results show that bone morphogenetic protein can induce new bone formation in primates within six weeks, and support the hope that it will be useful as a substitute for bone graft in man.

Animals↗

Dome osteotomy of the pelvis for osteoarthritis secondary to hip dysplasia. An over five-year follow-up study.

We performed Kawamura's dome osteotomy of the pelvis, with simultaneous distal transfer of the greater trochanter on 101 hips in 91 patients with osteoarthritis secondary to hip dysplasia. The mean age at operation was 30 years (15 to 55), and follow-up was for a mean of 8.3 years (5 to 14). Clinical evaluation using the Merle d'Aubigné score showed 92% excellent or good results. Radiologically, 91 hips had good acetabular remodelling and showed no signs of progression of osteoarthritis. In ten hips the osteoarthritic process progressed despite the osteotomy and six of these eventually underwent total hip replacement. Factors which were significantly associated with a poor outcome included an advanced stage of osteoarthritis, valgus deformity of the proximal femur, old age at the time of operation and postoperative persistence of abductor insufficiency.

Adolescent↗

The lumbar spine in spastic diplegia. A radiographic study.

Some radiological features of the lumbar spine of 84 patients with spastic diplegia were compared with 50 control subjects. The average age of the patients was 20.1 years (3 to 39). Spondylolysis of the fifth lumbar vertebra was found in 21%, four times more frequently than in normal subjects. No patient under nine years of age had spondylolysis and the frequency increased with age. The average angle of lumbar lordosis in spastic patients in the standing position was greater than in normal subjects, and increased with age. The patients had a decreased sacrofemoral angle which caused an increase in Ferguson's angle and explained the increased angle of lumbar lordosis.

Adolescent↗

Evoked spinal cord potentials for diagnosis during brachial plexus surgery.

We used evoked spinal cord potentials (ESCP) for intraoperative diagnosis in 17 cases of traumatic brachial plexus palsy. Forty spinal nerves were directly stimulated during exploration of the brachial plexus and ESCP recorded from the cervical epidural space were compared with simultaneously observed somatosensory evoked potentials (SEP) and myelographic findings. Both SEP and ESCP could be evoked in 21 spinal nerves but ESCP were always more distinct and five to ten times greater in amplitude than SEP. In four nerves, ESCP but no SEP were produced, suggesting that there was continuity from the nerves to the spinal cord. ESCP were obtained from two spinal nerves which appeared to be abnormal on the myelogram. The results show that intraoperative electrodiagnosis by epidural ESCP recordings can provide useful information on the lesions of traumatic brachial plexus palsy.

Adolescent↗

Disseminated pancreatic polypeptidioma.

Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon disease and its clinical features and responses to therapy are not well known. We present a 33-year-old woman with disseminated pancreatic polypeptidioma, who subsequently showed various signs and symptoms of metastases, including bone pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after the presentation. Responses to various therapeutic regimens including hepatic arterial embolization, radiation therapy, systemic chemotherapy, and administration of interferon-alpha or somatostatin analogue, are discussed. Particular note in this case is a prompt response of bone metastases to the radiotherapy.

Adult↗