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Biomedical subjects

K Ohno

Publications and source records attributed to K Ohno.

At least 361 records · Page 20Linked to original sources

Neuroradiological findings in the carbohydrate-deficient glycoprotein syndrome.

The carbohydrate-deficient glycoprotein syndrome is a newly recognised genetic disorder characterised by mental retardation, liver disfunction during infancy, cerebellar ataxia and atrophy, polyneuropathy, growth retardation, stroke-like episodes, and the appearance of carbohydrate-deficient fractions of multiple glycoproteins in the serum. The neuroradiological findings have been known as features of olivopontocerebellar atrophy. However, whether the abnormalities in the cerebellum and brain stem progress after birth is not known. We have carried out serial CT and MRI on three Japanese patients with this syndrome at different ages. A small cerebellum, with peculiar enlargement of the cisterna magna, and a small brain stem are present in infancy and atrophy of the anterior vermis and from before backwards in the cerebellar hemispheres seem to progress throughout early childhood.

Adolescent↗

Regulation of mRNA expression involved in Ras and PKA signal pathways during rat hypoglossal nerve regeneration.

Using in situ hybridization histochemistry and immunohistochemistry, the present study examines the cooperative regulation of transcription of molecules involved in the Ras-signal and the cAMP dependent protein kinase (PKA) pathways during peripheral nerve regeneration in rats. Injury to hypoglossal motor neurons resulted in an increase in extracellular regulated kinase (ERK, or MAP kinase) and ERK kinase (MEK, or MAP kinase kinase) mRNAs, but in a decrease in the expression of the catalytic subunits of PKA (C alpha and C beta) mRNAs. These results show the importance of the Ras-signal pathway in the nerve regeneration process and extend recent observation which suggested a cross-talk between the Ras and PKA pathways in vitro. The down-regulation of PKA may facilitate the activation of the Ras pathway which is located downstream of the growth factor receptor. The present study may suggest a possibility of regulatory talk between these two major signal transduction pathways.

Animals↗

Cell-cycle dependent biosynthesis and localization of p53 protein in untransformed human cells.

Localization of p53 in human cultured lymphocytes and in cultured skin fibroblasts was studied by immuno-fluorescent microscopy and post-embedded immunoelectron microscopy using Lowicryl K4M. In quiescent lymphocytes, p53 was found in small amounts in both the cytoplasm and the nucleus. p53 in the nucleus was found associated with the non-chromatin structure. At 24 h or 72 h of PHA stimulation, p53 increased markedly just beneath the plasma membrane and in the nucleus, which stained diffusely with anti-p53. In resting fibroblasts, small amounts of p53 were present in both the cytoplasm and the nucleus. After 16 h of stimulation of confluent-resting fibroblasts by trypsinization and replating, a phase just prior to the initiation of DNA synthesis, p53 slightly increased in both the cytoplasm and the nucleus. Afterwards, p53 was present predominantly in the cytoplasm, closely associated with the cytoskeletal actin filaments. In mitotic cells, p53 was distributed throughout the cytoplasm. When fibroblasts were extracted with saponin, p53 was still associated with the actin filaments, as well as mitochondrial membranes and granular structures of the nuclear matrix. Our data suggest that the initial increase of p53 in cells that enter the cell cycle through G1 first bind to the actin cytoskeleton, and that some of the p53 then move into the nucleus to initiate gene activation and DNA synthesis for cell proliferation. This implies that there is some functionally significant interaction between p53 and actin in the cells.

Cell Cycle↗

Experimental reconstruction of mandibular defects with vascularized iliac bone grafts.

PURPOSE: The study evaluated the processes of incorporation and bone remodeling after microsurgical transplantation of iliac crest grafts for mandibular defect reconstruction. MATERIALS AND METHODS: A defect in the mandibular angle measuring 2 x 4 x 1 cm was reconstructed in six Göttingen minipigs with a microvascularized iliac bone graft based on the circumflex artery. The animals were killed at 14, 28, and 56 days after transplantation and the healing process was histologically examined. RESULTS: Although a constant vascular supply to the graft was restored by the microvascular reanastomosis, necrosis occurred in the major part of the bone marrow. New bone formation from the graft was markedly delayed compared with that from the mandible. Some osteocytes and marrow survived after grafting, but the volume of iliac bone tended to decrease gradually over time. In the 56-day specimens, the border between the graft and the mandible was not clear. CONCLUSION: These findings indicate that survival of the vascularized iliac bone graft in the minipig is not complete.

Animals↗

The messenger RNAs encoding metabotropic glutamate receptor subtypes are expressed in different neuronal subpopulations of the rat suprachiasmatic nucleus.

Glutamate is the principal transmitter of retinal projections to the rodent suprachiasmatic nucleus, a circadian clock synchronized with the light-dark cycle through the activation of glutamate receptors of the ionotropic type. In vitro, an intracellular mobilization of calcium can be induced by glutamate within cells of the suprachiasmatic nucleus maintained in a calcium-free medium, suggesting a participation of metabotropic glutamate receptors coupled to phospholipase C. Using in situ hybridization histochemistry, we examined the expression of messenger RNAs encoding the mGluR1 and mGluR5 subtypes of metabotropic glutamate receptors in the suprachiasmatic nucleus of the adult rat and during postnatal development. In the adult, mGluR1 was expressed in a small subset of neurons segregated caudally within the ventrolateral subdivision of the nucleus, while mGluR5 was mainly expressed in ventrolateral neurons within the middle third of the nucleus. Both subtypes were expressed in morphologically similar small cells, but mGluR5 was also solely expressed in a small population of larger neurons located at the dorsalmost aspect of the ventrolateral subdivision. In addition, with mGluR1 probe silver grain clusters exhibiting a grain density close but below the significant level were observed throughout the ventrolateral subdivision of the nucleus. At birth, mGluR1 and mGluR5 were similarly expressed throughout the caudal half of the nucleus. The expression of mGluR1 increased during early postnatal development and exhibited an adult pattern at postnatal day 21. The expression of mGluR5 increased from postnatal day 7 and reached the adult pattern at postnatal day 45. These observations suggest that each subtype of metabotropic glutamate receptor coupled to phospholipase C underlies specific roles within the rat suprachiasmatic nucleus during postnatal development and in the adult. In the adult, ionotropic and metabotropic receptors likely co-expressed within neuronal subsets located in the retinal terminal field may have interactive and/or additive effects on intracellular calcium concentration. Metabotropic receptors may thus participate in the mediation of photic information conveyed to a subset of neurons. During postnatal development, metabotropic receptors may play a role in the maturation of glutamatergic synapses associated with the retinal input.

Animals↗

Effects of mazindol in two patients with Prader-Willi syndrome.

Two patients with Prader-Willi syndrome, including gross obesity with food-related behavior and mild mental retardation, are presented. One patient was an 11-year-old girl with the diagnosis of development delay, hypoactivity, and waxy skin with normal female karyotype. The other patient was a 15-year-old girl with the diagnosis of abnormal chromosome 15. Obesity had been present since early childhood, and it was difficult for them to manage their weight control by means of diet and exercise therapy. With 24-week mazindol administration, they demonstrated marked improvement in weight control during the early period and improvement in pathologic behavior without side effects. Mazindol was given orally, 1.0-2.0 mg/day, in one or two daily doses. Mazindol may prove to be useful in the treatment of patients with Prader-Willi syndrome.

Adolescent↗

Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity.

In five members of a family and another unrelated person affected by a slow-channel congenital myasthenic syndrome (SCCMS), molecular genetic analysis of acetylcholine receptor (AChR) subunit genes revealed a heterozygous G to A mutation at nucleotide 457 of the alpha subunit, converting codon 153 from glycine to serine (alpha G153S). Electrophysiologic analysis of SCCMS end plates revealed prolonged decay of miniature end plate currents and prolonged activation episodes of single AChR channels. Engineered mutant AChR expressed in HEK fibroblasts exhibited prolonged activation episodes strikingly similar to those observed at the SCCMS end plates. Single-channel kinetic analysis of engineered alpha G153S AChR revealed a markedly decreased rate of ACh dissociation, which causes the mutant AChR to open repeatedly during ACh occupancy. In addition, ACh binding measurements combined with the kinetic analysis indicated increased desensitization of the mutant AChR. Thus, ACh binding affinity can dictate the time course of the synaptic response, and alpha G153 contributes to the low binding affinity for ACh needed to speed the decay of the synaptic response.

Acetylcholine↗

Speech function following maxillectomy reconstructed by rectus abdominis myocutaneous flap.

Post-surgical maxillary defects have recently been reconstructed by microvascularized free flaps. However, few reports have evaluated the resulting speech function. This study compared the speech intelligibility of four maxillectomy patients who underwent reconstruction by rectus abdominis myocutaneous flaps (RAMCF) with that of four non-reconstructed patients who were treated with split-skin grafts and prostheses, to explore ways of achieving better speech function. Speech function was assessed by a Japanese language speech intelligibility test. Intelligibility scores ranged from 57.3% to 75.8% (mean, 70.4%) in the non-reconstructed group and from 66.2% to 77.2% (mean, 71.0%) in the reconstructed group. An analysis of articulatory manners and sites revealed that speech disorders resulted mainly from poor oronasal separation in the non-reconstructed group and from incorrect linguopalatal contact in the reconstructed group, especially for linguodentoalveolar and linguovelar sounds. Therefore, for higher speech function in the reconstructed group, dentoalveolar and palatal contours of the maxilla must be restored as closely as possible. This must also be done in patients whose maxillae are reconstructed by other types of microvascularized myocutaneous or cutaneous flaps that have similar postoperative palatal contours.

Adult↗

Effect of age and radiation on bone healing adjacent to hydroxyapatite placed in the tibia of rats.

This study investigated the effect of age and radiation on healing after implantation of hydroxyapatite granule in bone. Two groups of 16 male Wistar rats, aged 4 weeks and 2 years were used for this study. Hydroxyapatite particles were placed into the tibia 28 days after the delivery of 15 Gy of irradiation from a Linac source. The results of the present study suggest that an old rat was more vulnerable to the radiation than a young rat. It seemed that age might also be an important factor in the prognosis of the implanted hydroxyapatite in irradiated bone.

Age Factors↗

Fractures of the floor of the anterior cranial fossa.

We treated 28 patients with anterior cranial fossa floor fractures. Computed tomography (CT) scans adjusted to bone density disclosed three fracture types: (1) penetrating fractures through the orbita or ethmoid sinus; (2) simple or multiple linear fractures; and (3) extensive comminuted anterior cranial fossa floor fractures. Thirteen patients underwent emergent surgery for treatment of open depressed fractures (most common in type 3 fractures), for foreign bodies (in type 1 fractures), and for optic canal decompression. Large dural lacerations were always present in patients with type 3 fractures, and repairs were made with dural substitutes. Only one patient developed postoperative cerebrospinal fluid leakage. Nine (32%) of the patients in our series had visual involvement, but visual acuity recovered or improved in six patients. Our study shows that initial neuroradiologic evaluation with CT scans is important in patients with frontobasal fractures, and that secure dural repair during primary operation helps prevent cerebrospinal fluid leakage.

Adolescent↗

Immunohistochemical detection of progesterone receptors and the correlation with Ki-67 labeling indices in paraffin-embedded sections of meningiomas.

Female sex steroids may play a role in the proliferation of meningiomas. We investigated the progesterone receptor (PgR) immunoreactivities and the Ki-67 labeling indices in the formalin-fixed, paraffin-embedded sections of meningiomas from 39 patients. After autoclave pretreatment of the sections (which were immersed in a citrate buffer), the sections were incubated with the monoclonal antibody for the PgR and the MIB-1 monoclonal antibody for the Ki-67 antigen. In the meningiomas studied, the immunoreactivity for the PgR was moderately to strongly positive in 51%, weakly positive in 21%, and negative in 28%. The nuclear staining for the PgR was clear, and no tumors were positive for the estrogen receptor. The Ki-67 labeling indices of the PgR-positive meningiomas (mean +/- standard deviation, 2.35 +/- 2.12%) were significantly lower than those of the PgR-negative meningiomas (6.53 +/- 4.83%) (P < 0.05). Two meningiomas that had recurred more than once showed high Ki-67 labeling indices and negative immunostaining for the PgR. These findings indicate that the PgR status may be closely related to the growth potentials of the meningiomas. Our results confirm that the immunodetection of the PgR and the Ki-67 antigen on the paraffin sections of meningiomas provides a practical tool for estimating the biological behavior of the meningiomas.

Adult↗

Reproductive and developmental toxicity studies of toluene. I. Teratogenicity study of inhalation exposure in pregnant rats.

Toluene is a widely used solvent in industry which is the subject of abuse among the younger generation. A teratogenicity study of toluene by inhalation exposure was carried out in Sprague-Dawley rats and the effects on dams, fetuses and offspring were assessed. Pregnant females were exposed to 600 or 2000 ppm toluene for 6 h/day from day 7 to day 17 of pregnancy. The control group inhaled conditioned clean air under the same exposure conditions. Maternal exposure to 2000 ppm toluene caused significant toxic effects such as body weight suppression of dams and offspring, high fetal mortality and embryonic growth retardation, but no external, internal or skeletal anomalies were observed in the fetuses of any treated group. In addition, there were no differences in the results of pre- and postweaning behavioral tests of the offspring. However, no toxic or teratogenic changes which could be related to toluene exposure were apparent in the 600 ppm group. Further studies are warranted with toluene at higher concentrations applied during the period of organogenesis.

Abnormalities, Drug-Induced↗

Glutamate receptor gene family expressed in vestibular Scarpa's ganglion of rat.

The expression of glutamate receptor gene family in the vestibular Scarpa's ganglion (VG) of rat was determined using molecular biological techniques including reverse transcription (RT), polymerase chain reaction (PCR), amplification, DNA sequencing, and immunocytochemistry. Oligonucleotide primers were designed from the previously cloned sequences of the AMPA-selective glutamate receptors (GluR1-4), KA-selective glutamate receptors (GluR5-7, KA1&2), NMDA-selective glutamate receptors (NMDAR1&2), and metabotropic glutamate receptors (mGluR1-4). The cDNAs synthesized from the VG mRNAs were amplified with the specific primers for the subunits of each glutamate receptor gene family. Analysis of the nucleotide sequences of the amplified cDNAs identified the expression of GluR1-4, GluR5, and NMDAR1 in the VG. Sequence analysis identified the expression of all the four subunits of GluR1-4 in two alternative spliced versions named "flip" and "flop" in the VG. In an immunocytochemical study, a large number of VG neurons showed only GluR2/3-like immunoreactivity (IR) while GluR1- or GluR4-IR could not be determined in the VG. The present study suggested that the subunits of GluR1-4, GluR5, and NMDAR1 may be assembled into the hetero-oligomeric glutamate receptor complex in the VG and that the VG neuron-specific stoichiometry of the receptor complex may be functionally significant for the afferent signal transduction in the rat peripheral vestibular system.

Animals↗

[A case of thymic enlargement with hyperthyroidism].

A case of thymic enlargement with hyperthyroidism is reported. Hyperthyroidism was diagnosed in an 18-year-old woman, and a chest roentgenogram showed an anterior mediastinal mass. The mass had shrunk after anti-thyroid medication was given. This patient was thought to have thymic hyperplasia associated with hyperthyroidism.

Adolescent↗

[Alcohol drinking patterns among policemen in Shiga, Kyoto, Yamaguchi and Okinawa prefectures].

Alcohol drinking patterns among policemen in Shiga, Kyoto, Yamaguchi and Okinawa prefectures were surveyed using a questionnaire on alcohol drinking during 1987-88. The responses from 1812 (male) subjects (average age of 36) were compared to a similar survey in 1975-79. Drinkers accounted for 91.3% of all subjects, of which 6.6% drank daily, 65.6% drank more than once a week, 6.5% usually did not drink at all and 2.1% were abstainers. The percentage of daily drinkers decreased during the 10 years (13.5%) though the total number of drinkers slightly increased nationwide. Preferred beverages were, beer 39.9%, whisky 21.4% Japanese sake 17.9%, Japanese shochu 11.0%. The percentage of beer and Japanese shochu drinkers increased and that of Japanese sake decreased during the ten-year period. However, Japanese sake was the second most popular beverage in Shiga, Kyoto and Yamaguchi prefectures. In Okinawa, awamori (a strong kind of shochu) was the favorite. Especially, drinkers aged over 50 in Okinawa preferred awamori rather than beer. Though drinking frequency at home (banshaku) and parties (enkai) did not change, the consumption volume decreased during the ten-year period. In In particular, young drinkers drank less frequently at home. Intake increased with age. Our results indicate that drinking frequency and volume decreased during the ten-year period. In general, drinking frequency and volume is reported to have increased. This difference might be related to the character of a policeman's occupation.

Adult↗

[Niemann-Pick disease types A and B].

The molecular basis of Niemann-Pick disease, type A and B, has been confirmed by detection of mutations causing deficiency of the acid sphingomyelinase activity in the patients. It has been shown that mutations, which cause no activity of acid sphingomyelinase, are responsible for the type A and mutations which cause residual activities of the enzyme are responsible for the type B. Acid sphingomyelinase deficient mice have been established and confirmed to show a similar abnormality observed in human disease type A. These knock-out mice should serves as a useful model for somatic gene therapy. The mechanism of neuronal cell dysfunctions in the type A patients has not been well-characterized. Progress suggest that ceramide, which is produced by sphingomyelinase from sphingomyelin, is an important factor for signal transduction of cell differentiation. In addition, a lysosphingolipid (sphingosylphocholine), which accumulates in the tissues of the patients, has been reported to act as a strong mitogen in several types of cells through activating a transcription factor. AP-1. It is possible that abnormal phospholipid signaling is involved in the pathogenesis of neuronal cell dysfunction of Niemann-Pick disease type A.

Animals↗

[Niemann-Pick disease type C].

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder, but the basic defect has not yet been clarified. Diagnostic biochemical makers are intracellular accumulation of free cholesterol or the decreased esterification of exogenous cholesterol. The differences in the severity of defective esterification are related to the onset of the disease. Genetically, an abnormal gene is located on the human chromosome 18. Biochemically, many drugs, i.e. imipraine, progesterone and bafilomycin A1 are known to interfere with cholesterol esterification. Clinically, vertical supranuclear gaze palsy and cataplexy are specific symptoms. The filipin stain of the foamy cell in bone marrow is available for rapid diagnosis. Many therapies, i.e. dimethyl sulfoxide, low-cholesterol diet and transplantations, have been challenged but improvement of neurological symptoms have not been reported.

Animals↗