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Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 145 records · Page 8Linked to original sources

Syndrome of inappropriate antidiuresis seen twice in eight years.

We present a rare case of a 66-year-old woman with the syndrome of inappropriate antidiuresis (SIAD) accompanied by an empty sella whose symptoms were seen twice in the eight years after the administration of non-steroidal anti-inflammatory drugs (NSAID) or prochlorperazine. No diuresis or suppression of the plasma level of vasopressin (AVP) was observed after water loading upon cessation of the causative agents. Suppression of the renin-aldosterone system and a low plasma level of atrial natriuretic peptide (ANP) were observed during natriuresis. The plasma levels of AVP were increased after water loadings. Restriction of water intake ameliorated the symptoms and reduced hyponatremia. These findings suggest that NSAID or prochlorperazine caused overt SIAD twice in eight years. The water loading test itself stimulated the release of AVP and a suppression of the renin-aldosterone system played a more important role in natriuresis than ANP in this case.

Aged↗

Ventral spinal subdural hematoma--case report.

A 26-year-old male presented with a very rare spinal subdural hematoma which developed 3 days after minor trauma. Magnetic resonance imaging showed the very large hematoma, extending from the C-1 to the T-11 levels, ventral to the spinal cord. An attempt to remove the hematoma via a posterior approach on the next day failed. On the 3rd hospital day, the hematoma was partially removed at the C7-T1 intervertebral level through an anterior approach. Neurological signs of paraplegia, and urinary and bowel disturbances did not improve postoperatively.

Adolescent↗

Cochlioquinone A, an inhibitor of diacylglycerol kinase.

The effects of cochlioquinone A, isolated from Drechslera sacchari, were studied in vitro and in vivo. This compound specifically inhibited diacylglycerol kinase activity with Ki = 3.1 microM. The kinetics revealed that cochlioquinone A inhibited diacylglycerol kinase in competition with ATP, and non-competitively with diacylglycerol. The compound inhibited neither protein kinase C, epidermal growth factor receptor-associated protein tyrosine kinase, nor phospholipase C. Cochlioquinone A reduced the concentration of phosphatidic acid in T cell lymphoma with a half maximal concentration of 3 microM, and simultaneously augmented the phosphorylation of 80 kDa protein, a known substrate of protein kinase C. The degree of the phosphorylation of 80 kDa protein in the presence of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 microgram/ml). These results demonstrate that cochlioquinone A is a specific inhibitor of diacylglycerol kinase, which regulates the activity of protein kinase C.

Animals↗

Transforming growth factor beta 1 and beta 2 induce down-modulation of thrombomodulin in human umbilical vein endothelial cells.

To investigate the effects of transforming growth factor-betas (TGF-betas) on endothelial anticoagulant activity, we assayed thrombomodulin (TM) activity and antigen levels of human umbilical vein endothelial cells (HUVECs) incubated with TGF-betas in vitro. TGF-beta 1 suppressed surface TM activity and surface TM antigen levels maximally 12 h after incubation in dose-dependent manners. TGF-beta 2 was almost equipotent with TGF-beta 1 for the suppression of them. Both TGF-betas suppressed total TM antigen level in HUVECs, and the time course of the suppression was similar to that of the cell surface TM antigen level. The maximal reductions of TM mRNA levels by TGF-betas were observed at several hours ahead of those observed in both surface and total TM antigens levels, suggesting that the TGF-beta-mediated suppression of TM antigen of HUVECs is primarily regulated at the TM mRNA level. Our present work suggests that the down-modulation of TM level induced by TGF-betas in HUVECs contributes in vivo to promoting the thrombogenesis either at the sites of injury of vessel walls, such as atherosclerotic lesions where TGF-beta 1 is released from platelets, smooth muscle cells and monocytes, or at neovascular walls in tumors secreting TGF-beta 2.

Cells, Cultured↗

Effects of rhIL-1 alpha, rhIL-1 beta, and rhIL-1 receptor antagonist on erythroid progenitors (CFU-E and BFU-E) in human bone marrow.

Interleukin-1 (IL-1) is known to promote the production of colony-stimulating factor (CSF) and to possess the ability to protect the bone marrow suppression in granulocyte-macrophage (GM) series associated with radiotherapy or chemotherapy. There are conflicting reports concerning the action of IL-1 on erythroid progenitors, however, and no consensus has been established. In the present study, the influences of recombinant human IL-1 alpha (rhIL-1 alpha), rhIL-1 beta, and rhIL-1 receptor antagonist (rhIL-1ra) on erythroid progenitors (colony-forming units-erythroid, CFU-E; and burst-forming units-erythroid, BFU-E) in human bone marrow were studied. rhIL-1 alpha and rhIL-1 beta (1-1000 pg/mL) enhanced the CFU-E and BFU-E growth in human nonadherent (NA) bone marrow cells. rhIL-1 alpha and rhIL-1 beta also stimulated the formation of CFU-E and BFU-E in the NA and T cell-depleted bone marrow fraction. Moreover, rhIL-1 alpha and rhIL-1 beta enhanced the CFU-E and BFU-E in the CD34+ bone marrow cell fraction. These data and the results of limiting dilution analysis indicate that the stimulatory effect of IL-1 may consist of direct actions on erythroid progenitors. The enhancing effect of rhIL-1 alpha and rhIL-1 beta on erythroid progenitors was inhibited by rhIL-1ra. These data suggest that the stimulatory effect of IL-1 on CFU-E and BFU-E is mediated via the IL-1 receptor.

Antigens, CD↗

[Sisters with early onset hereditary dentatorubral-pallidoluysian atrophy of childhood--DNA analysis and clinicopathological findings].

Two sisters were presented, 16 years old and 12 years old, who showed similar clinical courses. They had had mental retardation since early childhood, and then ataxia began. They suffered from astatic and tonic seizures from early school age, which gradually evolved to intractable epilepsies. Spasticity progressed, and they deteriorated both physically and mentally. They revealed photo-sensitivity; convulsions were induced by the flickering of light. They were attacked by myoclonic seizures as well as choreoathetosis, and became bedridden by the latter part of the elementary school age. There were no fruitful results of any kind from the laboratory examinations for metabolic disorders. EEG showed that the epileptic seizure discharges were induced by photic stimulation; there were frequent 3-4 Hz diffuse spike-and-wave short bursts during waking and sleep periods. MRI findings of the elder sister at the age of 16 revealed remarkable diffuse brain atrophy. Gene analysis showed abnormally enlarged DNA fragments localized on the short arm of chromosome 12. This meant expanded CAG trinucleotide repeats. The younger sister died at the age of 12 years. Autopsy findings revealed degeneration of both dentatorubral and pallidoluysian pathways. There were especially remarkable gliosis and neuronal cell loss in the outer segment of globus pallidus, and moderate neuronal cell loss and typical grumose degeneration in the dentate nucleus. The diagnosis of juvenile-type hereditary dentatorubral-pallidoluysian atrophy was compatible with the pathologic findings. This diagnosis will be made possible before death through the understanding of the clinical symptoms and molecular genetics.

Adolescent↗

The Pmel 17/silver locus protein. Characterization and investigation of its melanogenic function.

The silver mutation in mice causes progressive graying of hair due to the loss of functional follicular melanocytes. Recently the silver locus gene (called Pmel 17) has been cloned; its encoded product shares homology with a chick melanosomal matrix protein and a bovine retinal pigment epithelial protein. Although the sequence of the silver gene and the correlation of its expression with pigment production have been reported, its function in melanogenesis is still unknown. In an effort to characterize that function, we have synthesized the predicted carboxyl-terminal peptide of the mouse Pmel 17 protein and generated a rabbit polyclonal antibody (alpha PEP13) to it; that antibody recognized the silver protein specifically. The immunoaffinity-purified silver protein lacked all of the known melanogenic catalytic activities which other tyrosinase-related proteins (TRP) have, nor did it appear to modulate any of those TRP activities. Metabolic labeling experiments demonstrated that the silver protein disappears in vivo within a few hours, indicating that it is rapidly degraded, or quickly processed to lose its carboxyl terminus. Cross-reactivity experiments showed that a recently reported anti-melanosomal matrix protein antibody (alpha MX) also recognizes the silver protein, although at a different epitope from that of alpha PEP13. Using Western immunoblotting, we analyzed subcellular fractions isolated from B16 F10 melanoma cells and found that the silver protein was rich in the melanosome fraction but was absent from coated vesicles which deliver TRPs to melanosomes. These results suggest that the silver locus product is a melanosomal matrix protein which may contribute to melanogenesis as a structural protein, although the possibility remains that it also has a novel catalytic function in melanogenesis.

Amino Acid Sequence↗

Induction of heat shock 70 mRNA by cadmium is mediated by glutathione suppressive and non-suppressive triggers.

The induction mechanism of heat shock 70 (Hsp70) gene by cadmium was investigated. In human amniotic WISH cells, Hsp 70 was induced by cadmium in a dose- and time-dependent manner. Cadmium-induced Hsp70 mRNA levels were enhanced 3- to 4-fold after depletion of intracellular glutathione (GSH) by either diethylmaleate or buthionine sulfoximine. Under these conditions, hydrogen peroxide might increase in the absence of substrate for glutathione peroxidase. We found that exogenous hydrogen peroxide alone induced Hsp70 which was further enhanced significantly after GSH-depletion by diethylmaleate. On the other hand, treatment of cells by diethyldithiocarbamate, an inhibitor of superoxide dismutase, induced Hsp70 2-fold over the level of control. This induction was further stimulated by cadmium even in the presence of GSH. Furthermore, a 4-fold increase of intracellular GSH by the treatment of cells with glutathione isopropyl ester did not diminish the cadmium-induced Hsp70. Gel mobility shift assays of nuclear extracts, from these differently treated cells, with oligonucleotide containing a promoter region of Hsp70 gene revealed that the levels of Hsp70 mRNA observed in the present study corresponded to the changes of transcription. These results imply that the induction of Hsp70 mRNA by cadmium is mediated at least partly via reactive oxygen species and attenuated by cellular GSH and that some part of cadmium-induced Hsp70 can not be eliminated by GSH, suggesting that multiple signals are functioning for this induction.

Base Sequence↗

Daidzein inhibits insulin- or insulin-like growth factor-1-mediated signaling in cell cycle progression of Swiss 3T3 cells.

An isoflavone compound, daidzein, inhibits the cell proliferation of Swiss 3T3 cells. Analysis of entry in S phase of Swiss 3T3 cells reveals that daidzein blocked cell cycle G1 phase progression 4.6 h after stimulation by bombesin plus insulin. After removal of daidzein, insulin or insulin-like growth factors (IGFs) reinitiate cell cycle progression of daidzein-blocked cells without further addition of bombesin. The order in the mitogenic action of insulin or IGFs is as follows: IGF-1 (5 ng/ml) >> IGF-2 (0.5 microgram/ml) congruent to insulin (1 microgram/ml). Studies in vivo of protein kinase activation by mitogenic stimulation reveal that the treatment with daidzein decreased the activation of a MAP2 phosphorylating protein kinase (MAP2 kinase). In vitro kinase assays showed that daidzein inhibits casein kinase II activity, but does not inhibit MAP2 kinase activity. Activation of casein kinase II by polylysine augments the activity of MAP2 kinase in digitonin-permeabilized 3T3 cells. These results suggest that daidzein blocked G1 phase cell cycle progression of Swiss 3T3 by inhibiting the activity of casein kinase II which is required for the commitment of mitogenic signal by insulin or IGF-1 in G1 phase.

3T3 Cells↗

Increase of hepatic mRNAS of profilin, actin and extracellular matrix proteins after carbon tetrachloride treatment and partial hepatectomy in rats.

The synthesis of liver collagen increases during the fibrotic process after administration of carbon tetrachloride and during regeneration after partial hepatectomy in rats. In the present study, we investigated the behavior of profilin and actin mRNA under such conditions. Profilin and actin mRNA increased after acute and chronic treatments of carbon tetrachloride, which is associated with the increase of fibronectin, type-III and -IV collagen mRNA. Furthermore, a simultaneous expression of profilin, actin and extracellular matrix proteins was observed during the regeneration of rat liver, that is, all mRNAs of these proteins showed biphasic peaks around 6 h and 48 h after partial hepatectomy. These results suggest that possible coupling might occur between the changes of extracellular matrix and the reorganization of actin cytoskeleton in vivo.

Actins↗

Analysis of lower aliphatic aldehydes in water by micellar electrokinetic chromatography with derivatization to 2,4-dinitrophenylhydrazones.

The analysis of lower aliphatic aldehydes in water following derivatization to 2,4-dinitrophenylhydrazones, was investigated by micellar electrokinetic chromatography (MEKC). The effects of the buffer pH and acetonitrile addition on the separation were investigated. Under optimized conditions the 2,4-dinitrophenylhydrazine (DNPH) reagent was completely separated from four DNPH derivatized aldehydes with high separation efficiency. DNPH-formaldehyde and DNPH-acetaldehyde were also completely separated from one another. Their relative standard deviation of migration times and peak areas were within 1.0% and 3.3%, respectively. The reproducibility of peak areas in this MEKC analysis was as good as that of high-performance liquid chromatography (HPLC) analysis with the same derivatization method. The recovery values from tap and river water were in the range of 97-102%. The detection limits of formaldehyde and acetaldehyde were 0.05 mg/L and 0.08 mg/L respectively.

Acetaldehyde↗

The effect of blood volume replacement on the mortality of head-injured patient.

In 77 head-injured and transfused patients, the amount of blood volume replacement (BVR) and patient outcome were retrospectively analyzed. They were divided into four groups of intracranial lesion by initial CT; acute subdural hematoma (SDH) with or without other lesions, traumatic subarachnoid hemorrhage only, epidural hematoma only and all other lesions. Result shows SDH is the most vulnerable to massive transfusion and BVR more than 5000 ml was fatal. Patients with other lesions have high possibility of survival even if BVR amounts to 7000ml. It is concluded, for patients resuscitated with excessive amount of transfusion (> 5000 ml), follow up CT and some vigorous treatment such as administration of hypertonic solutions should be scheduled.

Adolescent↗

Adaptation of hepatitis C virus for persistent infection in patients with acute hepatitis.

Nucleotide sequencing was used to analyze amino acid substitutions in the putative envelope 1 (E1) and envelope 2/nonstructural 1 (E2/NS1) regions of hepatitis C virus (HCV) to clarify a viral mechanism of persistent infection in three patients with acute hepatitis C who developed chronic hepatitis and two patients with chronic hepatitis. The HCV RNA titer in serum decreased markedly after the onset of acute hepatitis and then re-elevated. During this period, the substitution rate in the E2/NS1 region (especially in the hypervariable region located in the N-terminus) was significantly higher in patients with acute hepatitis than in patients with chronic hepatitis (P < 0.05). When patients with acute hepatitis C became persistent HCV carriers, the substitution rate decreased to the level seen in patients with chronic hepatitis. The amino acid substitution rate in the E1 region in the acute phase was similar to that found in the chronic HCV carrier state. These observations suggest that rapid substitution of the amino acid sequence in the hypervariable region of the E2/NS1 region may be one of the mechanisms of persistent HCV infection.

Acute Disease↗

Effects of neural blockade and general anesthesia on the laser-Doppler skin blood flow waves recorded from the finger or toe.

Effects of neural blockade and general anesthesia on the basic wave (BW) and the reflex wave (RW) among the laser-Doppler (L-D) skin blood flow waves recorded on the finger or toe were studied in 2 volunteers and 42 patients. The BW was continuous, rhythmic and independent of respiratory movements. The RW, which was induced by a deep inspiration or a snapping sound, was a transient marked reduction in blood flow. The BW was almost flattened and the RW was no longer induced at the finger under complete wrist block (n = 2), or under cervical or upper thoracic epidural anesthesia extended caudally over T7 (n = 2). On the other hand, the BW was still detected with reducing frequency and the RW could be provoked with one exception at the finger on the side with a sympathetic ganglion block at the C6 vertebral level (n = 14). The BW and RW at the toe were retained under lumbar subdural anesthesia (n = 6) as well. However, under the combination of lumbar subdural anesthesia and lower thoracic epidural anesthesia extending rostrally over T4 (n = 6), both the BW and the RW disappeared at the toe. In the course of deepening nitrous oxide/enflurane anesthesia (n = 10), the BW gradually reduced in frequency until it was almost flattened, and it became difficult to provoke the RW. L-D flowmetry of the finger or toe could be a useful clinical measure for detecting the presence or absence of sympathetic function controlling cutaneous vasomotion.

Adult↗

Cloning of cDNAs with possible association with senescence and immortalization of human cells.

Normal human diploid fibroblasts (HDF) have a finite life span in vitro and have been used as a model system for the study of in vivo aging. Little is known about how changes in gene expression may affect the immortalization of human fibroblasts. We looked for cDNA clones whose mRNAs were differentially expressed between mortal senescent SV40-transformed human fibroblasts (B-32) and the immortal counterparts (B-32F) derived from B-32 cells. We identified three cDNA isolates by subtractive differential hybridization with 32P-labeled cDNA probes from B-32 cells and B-32F cells. Nucleotide sequence analysis of these cDNA clones revealed that they were homologous to the human vimentin, a human mitochondrial gene and a human gene of unknown nature. Slot blot and Northern blot analyses demonstrated that the former two were preferentially expressed in senescent B-32 cells and the last one was less expressed in B-32F immortal cells.

Brain Chemistry↗

Coffin-Lowry syndrome with sensorineural deafness and labyrinthine anomaly.

A case of Coffin-Lowry syndrome is described. The child had the typical face and also soft and puffy hands with tapering fingers. His psychomotor development was retarded. Audiological tests revealed profound hearing impairment. Anomalous labyrinths were shown by CT scan of the temporal bones. It is inferred that deafness is one of the symptoms of this syndrome.

Ear, Inner↗