Biomedical subjects

A Sakurai

Publications and source records attributed to A Sakurai.

At least 127 records · Page 7Linked to original sources

PubMed1995

DIF-1, morphogen of Dictyostelium discoideum, induces the erythroid differentiation in murine and human leukemia cells.

The structure of morphogen of Dictyostelium discoideum, DIF-1, which was elucidated by Morris et al. proved to be closely similar to that of differanisole A which had been isolated by us from the metabolites of a simple eucaryote, Chaetomium, as the differentiation-inducer of murine and human undifferentiated tumor cells. This fact seemed to suggest the molecular structure playing an important part in differentiation and development beyond species. We have already examined whether differanisole A induces the differentiation in Dictyostelium discoideum, and it was morphologically and biochemically confirmed. In this study, we examined whether DIF-1 induces the differentiation in murine and human leukemia cells. Above the concentration of 2 micrograms/ml (6.5 microM), DIF-1 induced the differentiation in murine erythroleukemia B8 cells and in human leukemia K562 cells into the hemoglobin-synthesizing erythrocyte-like cells.

Animals↗

PubMed1995

Parvalbumin-positive small myelinated fiber bundles in anterior marginal areas in the human cervical cord.

During pathological examinations of amyotrophic lateral sclerosis (ALS) patients, we noticed that bundles of dense small myelinated fibers were relatively well preserved in the anterior marginal areas of the cervical cords in a few ALS patients with diffuse myelin pallor. Moreover, these fibers were strongly immunostained by anti-parvalbumin antiserum. These parvalbumin-positive fiber bundles were also seen in other ALS and non-ALS patients, and they were continuously traced up to the spinothalamic tract areas of the medulla oblongata. Therefore, it is suggested that these fiber bundles belong mainly to the ventral spinothalamic tract. We considered that these fiber bundles became conspicuous in shape since other areas in the anterolateral funiculus showed myelin pallor in such ALS patients.

Adult↗

PubMed1995

Carbachol-induced desensitization of rat basophilic leukemia (RBL-2H3) cells transfected with human m3 muscarinic acetylcholine receptors.

1. Carbachol-induced homologous desensitization of the secretory response was investigated by transfecting RBL-2H3 cells with cDNA encoding the human m3 muscarinic acetylcholine receptor (RBL-m3). 2. Exposure of RBL-m3 cells to 100 microM carbachol for 30 min in Ca2+-free medium inhibited the secretion induced by the subsequent addition of 10 microM carbachol plus Ca2+. 3. Desensitized cells bound [3H]quinuclidinyl benzilate with a similar Bmax and Kd to those of control cells. 4. The carbachol-induced transient increase in levels of inositol 1,4,5-trisphosphate was not changed by desensitization. 5. Homologous desensitization persisted when desensitized cells were permeabilized with Staphylococcal alpha-toxin.

Animals↗

PubMed1995

Combination therapy with traditional Chinese medicines and Streptococcus pyogenes products (OK 432) for endogenous tumor necrosis factor therapy. A preliminary report.

The antitumor activity of combination therapy with traditional Chinese medicines and OK432 (Streptococcus pyogenes) for cancer patients was investigated. Excellent antitumor activity of this treatment was achieved in one patient with hepatocellular carcinoma. The present report describes the clinical course of this patient and examines the contribution of production of tumor necrosis factor (TNF) and interferon-gamma (IFN). Endogenous production of TNF could be observed after drip intravenous injection of OK 432 in the serum of patients treated by previous oral administration of traditional Chinese medicines. The serum levels of IFN were very low and remained at almost undetectable levels under these conditions. The selective use of immunostimulants such as traditional Chinese medicines may be of value in combination with other therapies such as drip infusion of OK 432, in the treatment of advanced cancer or of aged patients because of the low toxicity. One patient out of 12 revealed a partial response as assessed by the antitumor activity. However, with this treatment, patients did become free from pain and a good performance status was supported.

Aged↗

PubMed1995

A novel point mutation (R243Q) in exon 7 of the c-erbA beta thyroid hormone receptor gene in a family with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is characterized by variable tissue hyporesponsiveness to thyroid hormones. Recently, a large number of different point mutations have been identified in the c-erbA beta thyroid hormone receptor (TR beta) in subjects with RTH. We describe a Japanese family with RTH with a novel point mutation in exon 7 of the TR beta gene. A single nucleotide substitution, guanine for adenine, was identified at the second position of codon 243 located in the hinge domain between the ligand binding and DNA binding domains in one of the two alleles of the proband and his mother, resulting in the substitution of the normal arginine (CGG) with a glutamine (CAG). Except for one family, point mutations so far described in RTH are clustered at exons 8-10 of the TR beta gene. This report presents a novel mutation in the characteristic portion in exon 7 of the TR beta.

Amino Acid Sequence↗

PubMed1995

Determination of the absolute configuration of urothion.

In order to determine the absolute configuration of urothion (1), the CD spectra of tri-4-chlorobenzoyl derivatives of 2-amino-6-[(3R)-3,4-dihydroxybutyl]pteridin-4(3H)-one and its (3S) compound were compared with that of the tri-4-chlorobenzoyl derivative obtained from the natural product. R-Configuration was concluded for the secondary hydroxyl group on the side chain of 1, which is the same configuration as that of molybdopterin (2). This supports the view that 1 might be a urinary metabolite of 2.

Circular Dichroism↗

PubMed1995

A case of initially undiagnosed hypoadrenalism presenting inappropriate secretion of anti-diuretic hormone.

The case of a 55-year-old woman with inappropriate secretion of anti-diuretic hormone (ADH) is reported. Her pituitary-adrenocortical function test showed normal values on admission, but when she recovered from hyponatremia, severe panhypopituitarism became overt. Her adrenal insufficiency was considered to have been "masked" by endogenous stimulation of the hypothalamus-pituitary-adrenal axis under severe stress. One should be cautious in estimating the pituitary-adrenal function of severely ill patients.

Adrenal Insufficiency↗

PubMed1995

Differences in cellular transport of tri-iodothyronine and thyroxine: cell cycle-dependent alteration of tri-iodothyronine uptake.

Cellular and nuclear uptake of tri-iodothyronine (T3) and thyroxine (T4) was examined using the cultured cell line derived from rat liver, clone 9, and rat hepatoma, dRLH-84. The saturable cellular uptake of T3 and T4 was demonstrated in these cells. First we examined the cell cycle-dependent alteration of thyroid hormone uptake. Cellular T3 uptake was minimal in the early G1 phase and increased in the late G1 phase, reaching a maximal level in the S phase. Alterations in nuclear T3 uptake were in accordance with the changes in cellular T3 uptake. On the other hand, cellular and nuclear T4 uptake was unchanged throughout the cell cycle, suggesting the T3 specificity of the cell cycle-dependent alteration of cellular hormone transport. Next we examined the effect of sodium butyrate on the cellular transport of thyroid hormones. After treatment with 5 mM sodium butyrate, cellular and nuclear uptake of T3 was increased, reaching a maximal level (four- to sevenfold increase) after 48 h. When cells were incubated for 48 h with various concentrations of sodium butyrate, T3 uptake was enhanced by 1 mM sodium butyrate, reaching a maximal level with 5 mM. Although cellular T4 uptake was also increased after treatment with sodium butyrate, the degree and time-course of the increase were different from those of T3. The maximal increase in cellular T4 uptake (two- to threefold increase) was attained 20 h after treatment. Despite the increase in cellular T4 uptake, nuclear T4 uptake was decreased after treatment with sodium butyrate. For both T3 and T4, the enhanced cellular uptake was due to the increased Vmax without changes in the Michaelis-Menten constant. These data indicate that cellular transport of T4 is different from that of T3 in rat hepatic cells.

Animals↗

PubMed1994

Two thyroid hormone response elements are present in the promoter of human thyroid hormone receptor beta 1.

Autoregulation of the human thyroid hormone receptor beta 1 (hTR beta 1) promoter was assessed by chloramphenicol acetyltransferase and luciferase reporter assays of transient transfections into COS1 and GH3 cells, DNase I footprinting, and gel shift assays. A 5'-deletional analysis of the promoter showed that the region between -906 and -839 and the sequence from -438 to -130 were positively regulated by T3 in COS1 cells cotransfected with an hTR beta 1 expression vector. We also transfected deletion constructs into GH3 cells and showed similar effects of T3 on the trans-activation of the reporters. DNase I footprinting showed a protected inverted palindromic thyroid response element (TRE) at position -890 to -866 in the distal fragment and a direct repeat at position -190 to -166 in the proximal fragment, which were protected by TRs. Mutation of each TRE significantly decreased the trans-activation of the promoter by T3. Gel mobility shift assays showed both proximal and distal TREs formed a retarded band with hTR alpha 1 or hTR beta 1 expressed in COS1 cells and reticulocyte lysates. The bands formed on the distal TRE and the proximal TRE appear to be preferentially formed by a TR homodimer and a heterodimer, respectively. Furthermore, the band formed on the distal TRE disappeared after adding T3 but that on the proximal TRE did not. These results indicate that hTR beta 1 expression is directly regulated by hTR alpha 1, beta 1, and their ligand through two TREs. The different structure of the TREs in this promoter suggests their physiological role in transcriptional regulation may be different.

Animals↗

PubMed1994

Response of hepatic proteins to 3,5,3'-tri-iodo-L-thyronine in diabetic rats.

In order to study whether peripheral action of thyroid hormones is altered in insulin deficiency and to elucidate the biological consequences of alteration of the cytosolic 3,5,3'-tri-iodo-L-thyronine (T3) binding protein (CTBP), we measured malic enzyme, T3-responsive nuclear n protein, CTBP and nuclear thyroid hormone receptor in the liver and kidney of streptozotocin (STZ)-induced diabetic rats that were treated with or without insulin and/or a receptor-saturating dose of T3. The following results were obtained. 1. Induction of malic enzyme by T3 was apparently diminished in diabetic rats. However, supplementary injection of insulin enabled previously given T3 to take effect in diabetic rats. 2. T3-responsiveness of other hepatic proteins (n protein and CTBP) was not altered by insulin in diabetic rats. 3. The level of n protein was increased by insulin in diabetic rats in vivo and in perfused rat liver, indicating that the hepatic n protein is a novel insulin-responsive protein. T3 and insulin increased the level of n protein non-synergistically in diabetic rat liver. 4. Hepatic nuclear receptor levels were not altered in diabetic rats. 5. Hepatic CTBP levels were decreased in diabetic rats. This was not due to the toxic effect of STZ. Low CTBP level was only partially increased by insulin after 30 days of diabetic period. Renal CTBP levels were not altered in diabetic rats with or without insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Painful bipartite patella in young athletes. The diagnostic value of skyline views taken in squatting position and the results of surgical excision.

Nine patients with painful bipartite patella associated with young athletes were evaluated clinically and radiologically at an average of 60 months (range, 21 to 145 months) after excision of accessory nucleus of the patella. All patients were male and between 14 and 21 years of age when they were operated on. The indications for excision of separated fragments of the patella included: failure of nonoperative treatment for more than 3 months; radiographic evidence of significant irregularities of the articular surface of the separated fragment of the patella; and symptoms severe and prolonged enough to warrant surgery. Skyline views taken with the patient in a squatting position with weight bearing showed a wider separation of the accessory fragment from the main patella than did the nonweight bearing skyline views. This appears to be an important and useful diagnostic feature in a painful bipartite patellae; the authors propose that this radiographic examination should be called a "squatting position test". Histologically, the interface between the accessory and main patella was fibrocartilaginous, and the adjacent bone tissue was clearly demarcated by a dense lamina, indicating that the initial lesion was probably a traction lesion. All patients returned to full sports activity at their previous highest level within 4 to 7 weeks. The excision of accessory bone appears to be a simple and reliable procedure for avoiding prolonged postoperative treatment, reducing the length of incapacitation, and minimizing the danger of permanent stiffness of the joint.

Adolescent↗

PubMed1993

Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum.

Bunina bodies (BBs), small eosinophilic intraneuronal inclusions in the remaining lower motor neurons, are the only pathologically specific hallmark of amyotrophic lateral sclerosis (ALS). During immunohistochemical examinations of spinal cords of patients with ALS, we noted that BBs were positive for anti-cystatin C (CC) serum. Immunoelectron microscopically, many small deposits of immunoperoxidase products were seen in the cytoplasms and dendrites of the anterior horn cells. Some immunoperoxidase products exhibited a tubular or vesicular pattern, but no rough endoplasmic reticula, mitochondria, lipofuscin granules or nuclei were detected. The presence of BBs, especially in the periphery, was marked. In an adult cat, CC was mainly localized in the medial aspects of Golgi apparatus and in lysosomes in the anterior horn cells of the spinal cord. BBs may represent an abnormal accumulation of unknown proteinous material associated with the Golgi apparatus.

Adrenal Medulla↗

PubMed1993

Differanisole A, an inducer of the differentiation of Friend leukemic cells, induces stalk cell differentiation in Dictyostelium discoideum.

Differanisole A isolated from the conditioned medium of a soil microorganism, Chaetomium strain RB-001, is an inducer of the differentiation of the Friend leukemic cells (mouse leukemia cells). The chemical structure of this substance is very similar to that of stalk cell differentiation-inducing factor (DIF) isolated from the cellular slime mould, Dictyostelium discoideum. We examined the effects of differanisole A on Dictyostelium HM44 cells, a mutant strain which is defective in DIF production, and found this substance to be an inducer of stalk cell differentiation in D. discoideum.

Animals↗

PubMed1993

Characterization of a novel mutant human thyroid hormone receptor beta in a family with hereditary thyroid hormone resistance.

OBJECTIVE: We wished to determine the abnormality responsible for Generalized Resistance to Thyroid Hormone in a family with this syndrome. DESIGN: Molecular biological studies were performed on a mutant human thyroid hormone receptor beta (hTR beta) cloned from fibroblasts of the patient. PATIENTS: The patient is from a previously reported family with typical features of Generalized Resistance to Thyroid Hormone, demonstrating goitre, elevated thyroid hormone levels, slightly elevated TSH, and retarded bone age. MEASUREMENTS: A cDNA for hTR beta 1 was cloned using specific oligonucleotide primers from fibroblast DNA. A mutant hTR beta 1 expression vector was constructed, and an in-vitro expressed mutant receptor was tested for T3 binding. Receptor binding to DNA was studied in a DNA cellulose assay and gel mobility shift assay. RESULTS: Two mutations were found in the cloned hTR beta. One was silent but the second changed arginine 438 to histidine. The mutation was present in RNA and genomic DNA, as shown by allele-specific amplification. The mutated receptor had reduced T3 binding affinity but demonstrated normal binding in a DNA cellulose assay and in a gel mobility shift assay. The receptor did not have altered heat sensitivity. CONCLUSIONS: In the T sibship with Generalized Resistance to Thyroid Hormone, resistance to thyroid hormone is apparently produced by a substitution of a histidine for arginine at amino acid 438, which causes reduced binding of receptor to T3, although the receptor remains able to bind to DNA and, for this reason, functions as a dominant negative in affected subjects who are heterozygous with one normal and one mutated allele.

Base Sequence↗

PubMed1993

Induction of cytosolic triiodo-L-thyronine (T3) binding protein (CTBP) by T3 in primary cultured rat hepatocytes.

Cytosolic 3, 5, 3'-triiodo-L-thyronine (T3)-binding protein (CTBP) plays an important role in the regulation of intracellular T3 translocation from cytoplasm to the nuclear T3 receptor. We examined whether the CTBP activity could be induced by T3 or not in cultured hepatocytes prepared from thyroidectomized rats. CTBP activity was not detected in primary cultured hepatocytes from thyroidectomized rats. However, the protein was induced by the addition of T3 to the culture medium. The increase in the activity of CTBP was time dependent and the maximal level was obtained by 48 h in the presence of 300 nM T3. CTBP activity was also increased by retinol (35 microM) or by 1,25-(OH)2-vitamin D3 (10 nM). On the other hand, the activity of malic enzyme (ME) was induced by the addition of T3 to the culture medium. The maximal activity of ME was obtained by 48 h in the presence of 300 nM T3. The increase in ME activity was also induced by retinol or 1,25-(OH)2-vitamin D3. These results suggested that not only ME activity but also CTBP activity is induced by T3. Further, retinol and vitamin D3 have similar effects on the induction of CTBP activity and ME activity.

Animals↗

PubMed1993

n-Butyrate enhances induction of thyroid hormone-responsive nuclear protein.

Effects of n-butyrate on nuclear thyroid hormone receptors and on thyroid hormone-responsive nuclear protein were investigated by means of a perfusion system in rat liver. Treatment with 5 mM n-butyrate resulted in an increase (150%) in the maximal binding capacity of 3,5,3'-L-triiodothyronine (T3) nuclear receptors without altering the affinity of receptor for T3. However, further perfusion for 4 h decreased the number of the receptors to the control level. n-Butyrate increased the amount of acetylated histone H4. The ability of nuclear T3 receptors to bind to core histones was diminished by acetylation of the core histones. Thyroid hormone-responsive nuclear protein (n protein) was increased by T3. The induction of the n protein by T3 was augmented by n-butyrate. These results suggested that n-butyrate modulates thyroid hormone-responsive gene expression in rat liver via the increased number of nuclear receptors or changes in the chromatin constitution.

Acetylation↗

PubMed1993

A further study on the left-right asymmetry of the planum temporale.

By means of a rubbed copy method using India ink and an image-analysis system (IBAS 2000), the areas of 106 left-right plana temporalia were compared using fixed brains of both sexes. The left planum was of a larger size than the right planum in two-thirds of the cases. This result was confirmed statistically by the least-squares analysis of variance method (p < 0.01).

Adult↗

PubMed1993

[Magnetic stimulation of the facial nerve].

Intracranial activation of the facial nerve and the face-associated motor cortex are now possible with noninvasive magnetic stimulation techniques. Compound muscle action potentials (CMAPs) and the Blink reflex, in response to magnetic stimulation, were investigated. Subjects were 10 normal controls and 2 Bell's palsy patients. CMAPs were elicited in the orbicularis oris muscle by magnetic stimulation at the parieto-occipital skull and stylomastoid foramen. Furthermore, CMAPs were evoked by a magnetic coil oriented over the cortex. CMAP recording was possible with magnetic stimulation and the latencies of CMAPs at the parieto-occipital skull were slightly greater than those at the stylomastoid foramen. In 10 normal subjects, the mean onset latency following transcranial magnetic stimulation of the facial nerve at the parieto-occipital skull was 5.07 msec (SD = 0.40), while transcutaneous latency at the stylomastoid foramen was 2.77msec (SD = 0.539). In the blink reflex, R1 latency was 10.99 msec (SD = 1.27), ipsilateral-R2 latency was 37.46 msec (SD = 2.57), and contralateral-R2 latency was 38.925 msec (SD = 3.20). The blink reflex thus had a configuration similar to that evoked by conventional electrical stimulation. In the patients with Bell's palsy, CMAPs elicited by magnetic stimulation were of low amplitude with normal latency. However, in the blink reflex, only a contralateral R2 response could be recorded, and R1 and ipsilateral-R2 showed no response to stimulation at the affected side. Investigation of patients with Bell's palsy using this technique may therefore prove useful in the evaluation of peripheral facial nerve disorders.

Action Potentials↗