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Biomedical subjects

S Hirayama

Publications and source records attributed to S Hirayama.

At least 19 recordsLinked to original sources
PubMed2001

LR11, a mosaic LDL receptor family member, mediates the uptake of ApoE-rich lipoproteins in vitro.

Since the molecular identification of the low density lipoprotein receptor (LDLR), an ever increasing number of related proteins have been discovered. These receptors belonging to the LDLR family are thought to play key roles in lipoprotein metabolism in a variety of tissues, including the arterial wall. We have discovered that the expression of a 250-kDa mosaic LDLR-related protein, which we termed LR11 for the presence of 11 LDLR ligand-binding repeats, is markedly induced in smooth muscle cells in the hyperplastic intima of animal models used for the study of atherosclerosis. Here, we demonstrate that the human LR11, when overexpressed in hamster cells, binds and internalizes 39-kDa receptor-associated protein (RAP), an in vitro ligand for all receptors belonging to the LDLR family. Furthermore, LR11 binds the apolipoprotein E (apoE)-rich lipoproteins, beta-very low density lipoproteins (VLDLs), with a high affinity similar to that of other members, such as the LDLR and VLDL receptor. RAP and beta-VLDL compete with each other; however, other serum lipoproteins are not able to inhibit their binding. LR11 shows specific binding of apoE-enriched HDL prepared from human cerebrospinal fluid as well as of beta-VLDL, suggesting that the apoE content of lipoproteins is most likely important for mediating the high-affinity binding to the receptor. LR11-overexpressing cells are able to internalize and degrade the bound beta-VLDL; these cells also show increased accumulation of cholesteryl esters when incubated with beta-VLDL. Incubation for 48 hours with beta-VLDL of LR11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets. Taken together, LR11, a mosaic LDLR family member whose expression in smooth muscle cells is markedly induced in atheroma, has all the properties of a receptor for the endocytosis of lipoproteins, particularly for the incorporation of apoE-rich lipoproteins.

Animals↗
PubMed2001

Sarcoid reaction in primary tumor of bronchogenic large cell carcinoma accompanied with massive necrosis.

A 49-year-old woman consulted our hospital for evaluation of a tumor with cavitation in the S6 segment of the right lung. She was given a diagnosis of pulmonary tuberculoma because percutaneous needle aspiration cytology revealed epithelioid cells with a background of necrosis. However, a diagnosis of large cell carcinoma with central necrosis (p-T2NOM0) was established by thoracoscopic lung biopsy six months later. Pathological findings of surgical resection specimens showed that epithelioid cell granulomas adjacent to the neoplasm had a sarcoid reaction and the necrosis was related to the rapidly growing tumor because there was no clinical evidence of systemic sarcoidosis and pulmonary mycobacterial or fungal infection. This is the first report in which sarcoid reactions were recognized in a primary large cell carcinoma.

Antitubercular Agents↗
PubMed2001

Time course of leucine-induced 4E-BP1 and S6K1 phosphorylation in the liver and skeletal muscle of rats.

The purpose of the current study was to assess the involvement of the branched-chain amino acid leucine in the regulation of translation initiation in the liver and to compare the time course of leucine action on the translation initiation in the liver and skeletal muscle of rats. The phosphorylation of the eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1) frees eIF4E and stimulates protein synthesis by accelerating translation initiation. Phosphorylation of the 70-kDa ribosomal protein S6 kinase (S6K) is thought to be involved in regulating the synthesis of certain ribosomal proteins and other selected proteins with polypyrimidine clusters near the transcription start site. Food-deprived (18 h) male rats were orally administered 135 mg/100 g body weight L-leucine and sacrificed at 0, 1, 3, or 6 h after administration. The oral administration of leucine resulted in an enhanced phosphorylation of 4E-BP1 and S6K1 in both the liver and skeletal muscle. A time-dependent change in the phosphorylation state of 4E-BP1 and S6K1 was more acute in the skeletal muscle than in the liver and closely paralleled the changes in plasma leucine concentration. Our results indicate that the primary mediator in 4E-BP1 phosphorylation and S6K1 phosphorylation by the oral administration of leucine is an increase in the plasma concentration of leucine. Furthermore, our findings suggest differential sensitivity in the tissue response to oral administration of leucine.

Administration, Oral↗
PubMed2001

[Prevalence of asthma in adults in Menda town rural-mountain area in Japan].

Several reports have suggested that the prevalence of asthma in adults is currently increasing. However, recent prevalence of asthma has not reported in Japan, especially in rural-mountain areas. To investigate the prevalence of asthma in adults in Japan, we conducted clinical epidemiological research on 5066 inhabitants of Menda town, in a rural-mountain area of Japan. The study population comprised 98.7% of adults in the town, including senior high school students whose age were more than 15 years old. The prevalence of asthma among adults was 3.6%. The ratio of prevalence in males to prevalence in females was 1.44. Peaks prevalences were observed in the age ranges of 15-19 and > 70 years old in males, and 15-19, 40-49 and > 70 years old in females.

Adolescent↗
PubMed2000

Differential expression of LR11 during proliferation and differentiation of cultured neuroblastoma cells.

An involvement of the low density lipoprotein receptor (LDLR) gene family in both intracellular signal pathways for neural organization and metabolic pathways for lipoprotein homeostasis is now well established. The discovery of LR11, a mosaic LDLR family member offers the opportunity to gain new insights into receptor multifunctionality. Here, we studied the proliferation-dependent expression of LR11 mRNA and protein using two cultured cell lines, IMR32 neuroblastoma and PC12 pheochromocytoma. Within 24 h, the LR11 protein rose 1.9-fold in proliferating IMR32 cells, and increased further to 5.3-fold at 72 h. This conformed with a transcript level increase of 4.7-fold at 72 h in the proliferating cells. On the other hand, under differentiation conditions, a 2.9-fold increase was observed within 24 h, but at 72 h thereafter the protein levels decreased to 60% of control. The transcript also increased to 1. 8-fold within 24 h, and then decreased to 1.1-fold at 72 h. In order to assess the transcriptional activities of the LR11 gene, we identified the 5'-flanking region of the murine LR11 gene. Transfection of IMR32 and PC12 cells with plasmids containing the whole or deleted fragments of 5'-flanking region showed that element(s) responsible for the above described different transcriptional activities are located in the upstream sequence between -861 and -396. Thus, the transcription of LR11 in these two cell systems is regulated differently during proliferation and differentiation, suggesting that the multifunctionality of LR11, as well as other LDLR family members, for rapid cell growth in malignant cells and neural outgrowth in cultured neurons, respectively. The possible involvement of LR11 in cellular proliferation and differentiation sheds new light on its functions in neurons, malignant, and vascular cells.

Animals↗
PubMed2000

Differential regulation of leptin receptor expression by insulin and leptin in neuroblastoma cells.

Leptin exerts its effects by interacting with specific membrane receptors (Ob-R). We studied the exact localization of long intracellular domain form (Ob-Rb) in human brain. In addition, we analyzed the regulatory features of Ob-Rb expression in two neuroblastoma cell lines. The Ob-Rb mRNAs were abundant in putamen, frontal lobe, medulla, cerebral cortex, cerebellum, thalamus, hippocampus, corpus callosum, caudate nucleus, and amygdala, indicating that Ob-Rb transcripts are expressed differently from that of other Ob-R isoforms. In SK-N-MC cells, the expression of Ob-Rb mRNA was induced by increasing doses of insulin, and the maximum amount of mRNA expression was 9.4-fold higher in the presence of insulin (100 nM for 24 h), compared to the absence of insulin. In IMR32 cells, the transcripts were increased 4.0-fold when cells were incubated with 1 nM of insulin for 48 h. In contrast, Ob-Rb expression in IMR32 cells decreased to 18% of control following a 24-h incubation period with 50 ng/mL of leptin, compared to incubation in the absence of leptin. These results indicate that expression of Ob-Rb is differentially regulated by inhibitory signals of energy balance in neuroblastoma cells. The identification of the novel regulatory mechanisms involving the Ob-Rb isoform by insulin and leptin now makes it possible to elucidate the underlying mechanisms involving increased food intake and uncontrolled energy balance associated with leptin resistance in obese individuals.

Brain↗
PubMed2000

Diametral tensile strength and compressive strength of a calcium phosphate cement: effect of applied pressure.

The diametral tensile strength (DTS) and compressive strength (CS) of a calcium phosphate cement comprised of tetracalcium phosphate and dicalcium phosphate anhydrous were studied. Cement powder and water were mixed at a powder/liquid ratio of 4.0. The resulting cement pastes were placed in molds and a pressure ranging from 0-2.8 MPa was applied for various lengths of time (0.5-24 h). DTS and CS measurements were conducted on 24-h wet samples. The strength was found to be significantly (p<0.05) affected by the pressure but not by the time. Samples prepared under a pressure of 0.7 MPa had a mean DTS value of 10.8+/-1.0 MPa (n = 5), which is comparable to the values reported in the literature for the same cement prepared under similar conditions. In contrast, the mean CS value obtained in the present study, 66.1+/-5.0 MPa (n = 5), was significantly higher than the value (51+/-4.5 MPa) previously reported. The higher CS may be attributed to an improved mold design that may reduce sample damage during demolding, and to the use of a loading device that applied a constant pressure to the sample during setting. The average standard deviation of the mean for the 19 DTS sample groups (n = 5 in each group) was 1.1 MPa, corresponding to 9.6% of the mean DTS value. The average standard deviation of the 7 CS sample groups (n = 5 in each group) was 4.5 MPa, corresponding to 7.1% of the mean CS value. Published 2000 John Wiley & Sons, Inc.

Bone Cements↗
PubMed2000

Marked elevation in serum apolipoprotein E in a case of heterozygous cholesteryl ester transfer protein deficiency.

The subject was a 57-year-old Japanese woman with a body mass index of 21.2 kgm(-2). Her serum total cholesterol (TC), triglycerides (TG) and HDL-cholesterol levels were 7.11 mmoll(-1), 0.53 mmoll(-1) and 2.05 mmoll(-1), respectively. She had a marked increase of serum apolipoprotein (Apo) E concentration of 25 mgdl(-1) with normal concentrations of serum Apo A-I, A-II, B, C-II and C-III. Polymerase chain reaction-restriction fragments length polymorphism analysis of the cholesteryl ester transfer protein (CETP) gene from this subject revealed the heterozygous nucleotide change causing a Asp442 to Gly substitution (D442G) in the CETP protein. For comparison, 11 unrelated female subjects with this mutation (age, 57+/-5.1 years; BMI, 22+/-1.5 kgm(-2); TC, 7.23+/-1.16 mmoll(-1); TG, 1.44+/-0.80 mmoll(-1); HDL-C, 2.47+/-0.53 mmoll(-1)) were found to have a serum Apo E concentration of 7+/-1.5 mgdl(-1), about a third of the patient's concentration. The lipoprotein profile of the proband's serum analyzed by disk polyacrylamide gel electrophoresis showed a trace amount of VLDL. A vitamin A fat-loading test showed little increase in serum triglycerides and retinyl palmitate levels compared with control subjects at 2, 4 and 6 h after fat loading. Ultracentrifugation analysis of her serum revealed no detectable Apo E in the VLDL fraction but showed a large amount of Apo E in the HDL fraction, in contrast to a normal control, who had Apo E in the VLDL fraction as well as in the HDL fraction. Sequence analysis of the Apo E gene from the subject showed no nucleotide changes in exon 3 and exon 4, which code the mature Apo E protein, indicating there is no structural abnormality in the Apo E protein. Direct sequence analysis of the LDL receptor gene also did not show any nucleotide change. Based on these findings, it was hypothesized that the marked increase of Apo E in the patient's serum was caused by a decreased transfer of Apo E from HDL particles to TG-rich lipoproteins or impaired uptake of Apo E-containing HDL by LDL receptor or remnant receptor, due presumably to a dysfunction of these receptors in the patient.

Apolipoproteins E↗
PubMed1999

Expression of LR11, a mosaic LDL receptor family member, is markedly increased in atherosclerotic lesions.

Receptors belonging to the LDL receptor (LDLR) family are thought to play key roles in lipoprotein metabolism in a variety of tissues, including the arterial wall. Here, we report that the expression of a 250-kDa mosaic LDLR family member, which we called LR11 for the presence of 11 ligand-binding repeats, is markedly induced during the process of atherogenesis in 2 animal models. Analysis by reverse transcription-polymerase chain reaction and RNase protection assays revealed that LR11 transcript levels rise in rabbit aortas displaying atheromatous lesions after the rabbits have been fed a high-cholesterol diet. Immunohistochemistry demonstrated that the highest induction of LR11 occurs in intimal smooth muscle cells (SMCs), followed by medial SMCs close to the intimal border of the atheromatous lesions. Experimental intimal hyperplasia by endothelial denudation showed that LR11 mRNA levels were also increased in the arteries after balloon injury, with the transcripts localized primarily in the hyperplastic intimal layer. In agreement with the correlation of LR11 induction during increased cell proliferation, cultured SMCs showed an increase in LR11 expression in the proliferative phase. Furthermore, Northern and Western blot analyses showed that medium conditioned by the monocyte-macrophage cell line THP-1 enhanced LR11 expression in cultured SMCs. These findings suggest that upregulation of LR11 might be contributing to the pathological roles of intimal and medial SMCs during arteriosclerotic lesion development and provide the first insight into the as yet unknown functional significance of this intriguing LDLR family member.

Angioplasty, Balloon↗
PubMed1999

[Levofloxacin concentrations in serum, sputum and lung tissue: evaluation of its efficacy according to breakpoint].

The levels of levofloxacin (LVFX) in the serum, sputum and lung tissue were measured by a high-performance liquid chromatography method, and the penetration ratio of LVFX into respiratory tissue was investigated. The subjects of this study were 23 patients under pulmonectomy or brochoscopy. LVFX at the dose of 200 mg was given orally and specimens were collected as follows; serum at 2, 3 and 5 hours after, sputum at 2 hours after, and lung tissue at 3 and 5 hours after the administration, respectively. The mean level of LVFX in lung tissue at 3 hours was 3.91 +/- 2.33 micrograms/g, and those in sputum and in serum at 2 hours were 0.71 +/- 0.63 and 2.08 +/- 1.01 micrograms/ml, respectively. A very strong correlation was demonstrated between the level of LVFX in lung tissue and that in serum (p < 0.0001), but correlation between those in sputum and in serum was not significant. The penetration ratio of LVFX into lung tissue was 217.2% and that into sputum was 4.05%. Based on the results of this study, the breakpoints (BPs) of LVFX for pneumonia and chronic respiratory tract infections were calculated to be 4 micrograms/ml and 1 microgram/ml, respectively. It was concluded that penetration of LVFX into lung tissue was satisfactory, and the tissue level of LVFX exceeded greatly the MIC90s against the typical pathogenic bacteria of respiratory tract infections. Taking the excellent BP for pneumonia, 4 micrograms/ml, into consideration, it was thought that LVFX is an effective antibacterial agent against pneumonia and other respiratory tract infections.

Adult↗
PubMed1998

Developmental regulation of LR11 expression in murine brain.

Receptors belonging to the low density lipoprotein receptor (LDLR) superfamily play important biological roles in addition to mediating lipoprotein metabolism. The recent discovery of a novel mosaic LDLR family member by us (Yamazaki H., Bujo, H., Kusunoki, J., Seimiya, K., Kanaki, T., Morisaki, N., Schneider, W.J., and Saito, Y. (1996) J. Biol. Chem. 271, 24761-24768) and others, which we termed LR11, offers the opportunity to gain new insights into receptor multifunctionality. The predominant expression of LR11 in brain and the presence of elements found in neural adhesion molecules suggested a function(s) in the central nervous system (CNS). In order to gain information about this complex receptor in an accessible system, we have molecularly characterized the murine LR11 and report on its detailed localization and developmental expression pattern. The primary sequence of the murine protein further establishes that LRlls are among the closest relatives within the LDLR family and that brain is the predominant site of expression. In situ hybridization showed that neuronal bodies such as Purkinje cells in the cerebellum and other neurons in the hippocampal formations and the cerebral cortex are particularly rich in LR11 transcripts. The developmental pattern of LR11 expression in brain, which peaks at 2 weeks, is in contrast to those of two other LDLR family members, the very low density lipoprotein receptor and the LDLR. During early development, murine LR11 expression levels are highly dependent on neural cell types. These findings are compatible with function(s) of LR11 in neural organization and, possibly, pathogenesis of degenerative brain diseases. In addition, detailed knowledge of LR11 biology will help to elucidate the roles of other mosaic proteins that share with LR11 elements whose function is not yet known.

Amino Acid Sequence↗
PubMed1998

[Psychosocial evaluation on the correct recollection of periodic medical checkups of workers. 2. Long-term change in the recalled results of medical checkups].

A self-administered questionnaire study of 333 workers (male 253, female 80) in a manufacturing company was carried out one month after informing the workers of the results of their medical checkups in 1993. The questionnaire included several items such as recalled abnormal findings of health examination and ways of overcoming the abnormal findings, recalled results of their medical checkups in 1992, self-confidence in their recollection of the results, and the usefulness of medical checkups. The following were investigated: the relationship between actual as well as recalled results of medical checkups in 1992 and the recollection of them after one year, the effects of examinations after medical checkups in 1992 on their recollection of the checkup results after one year, the effects of actual as well as recalled 1992 checkup results on the recollection of the results one month after informing the workers of the results of their medical checkups in 1993, assurance of correct recollection of the results, the relationship between the usefulness of medical checkups, explanation of abnormal findings and the percentage of correct answers to the results of medical checkups in 1993 one month after informing the workers of their results. It was found that the percentage of correct answers to the results after one year was significantly lower than that after one month in 1992. The rate decreased with the increase in the number of abnormal items in medical checkups. Moreover, the rate also decreased when the results were abnormal. Further examinations in addition to the medical checkups influenced their recollection somewhat after one year. The results that the workers still remembered in 1992 had a stronger effect on their recalling the results one month after informing them in 1993 than the actual results in 1992. The workers' confidence in their recollection of the results was untrustworthy in the same way as their recollection of the results, and they were not able to maintain the recollection of the correct results, although many of the workers realized the usefulness of the medical checkups. Our results suggest that explanation of abnormal medical findings in 1993 was effective because the percentage of partial concordance between actual and recalled results was much higher in the workers who received the explanation than in the workers who did not receive it.

Adult↗
PubMed1997

A case of a non-insulin dependent diabetic patient with regular spontaneous hypoglycemic attacks, which were due to insulin-binding antibodies induced by human insulin therapy.

A 74-year-old diabetic patient had been treated with oral hypoglycemic agents from the age of 40 years until the age of 72, when his treatment regimen was changed to human insulin. He began experiencing hypoglycemic attacks 14 months after the initiation of insulin therapy. He continued to experience hyperglycemia every morning and hypoglycemia every day at 5:30 p.m. even after insulin therapy was withdrawn. His plasma levels of C-peptide immunoreactivity, total and free immunoreactive insulins were 4.2 ng/ ml, 740 microU/ml and 141.8 microU/ml, respectively. His 125I-insulin binding rate was 94.4%. These findings suggest that his hypoglycemic attacks may have been due to insulin antibodies. Analysis revealed that insulin binding antibodies belonged to IgG with kappa light chains. The patient's genotype was HLA-DR4. He had not received animal insulin or any medications containing a sulfhydryl group. Although the IgG antibody was produced against injected human insulin, his HLA type and the characteristics of his antibodies resembled those of a patient with insulin autoimmune syndrome (IAS). We hypothesize that this patient represented a rare instance of a patient constitutionally similar to a patient with IAS, but whose hypoglycemic attacks resulted from the antibodies induced by the administration of human insulin. This case seems to be the first one with hypoglycemic attacks due to anti-human insulin antibody produced by human insulin therapy.

Aged↗
PubMed1997

[The relationship between workers' attitudes towards health, lifestyle and mental health].

In order to investigate the relationship between health practices, various psychosocial factors, and mental health, a survey was conducted by means of a self-rating questionnaire on 424 industrial workers. The questionnaire included items concerning Goldberg's 12 selected items from the Japanese version of the General Health Questionnaire, the Type A scale used in the Framingham study, Breslow's 7 health practices, and other original psychosocial, health practicing items. A total of 391 or 92.2% responded to the questionnaire. Among them, 354 (266 males and 88 females) complete responders to the GHQ were analysed for the present study. As a result, several factors such as decrease in age, perceived present illness, worsening of perceived health status, increase in anxiety concerning health, exacerbation of alcohol and smoking related behaviour, decrease in physical exercise, reduction of Breslow's 7 health practices, perceived stress and difficulty in dealing with stress, increase in stress content, negative and malfunctional coping strategies, and decrease in relaxation were, according to the GHQ scores, related to negative mental health. Furthermore, Type A scores were significantly correlated to GHQ scores, the number of stress factors, and Breslow's 7 health practices in males, but they were weak or had no correlation in females. It is considered that favorable health practices and attitudes towards health might help to maintain positive mental health, but further analysis is needed to determine their causal relationships because of the cross-sectional design of the present study.

Adaptation, Psychological↗
PubMed1997

[Psychosocial evaluation on the correct recollection of periodic medical checkups of workers. 1. The ratio of correctly recalled results of medical checkups].

To investigate the usefulness of a periodic medical checkup at the workplace from the standpoint of remembering the results, a survey was performed by a self-rating questionnaire on 424 industrial workers in a certain manufacturing company. The questionnaire included several items, such as their recalled abnormal medical findings and follow-up toward them, Breslow's 7 health practices, Goldberg's 12 selected items from the Japanese version of the General Health Questionnaire, and other original health related items. The study was conducted a month after the workers received their results. A total of 391 (290 males and 101 females) or 92.2% responded to the questionnaire. Several factors, such as age, gender, the type of occupation, and perceived health status were significantly correlated to the recalled results of medical checkups, but, only age and the way of observing the results were in accordance with the actual results. Only forty-nine percent of the responders correctly remembered their results. Age and perceived health status were significantly correlated to the exact recollection of the results. In particular, those who had poor perceived health status tended to have a wrong understanding of their medical results. Furthermore, there were those with the highest averaged GHQ scores who responded as having some abnormal findings even though no abnormalities were discovered in the medical checkups. On the other hand, there were those with the lowest averaged GHQ scores who answered that they had no abnormal findings even though some abnormalities were revealed in the medical checkups. The frequency of correct follow-up of the results was lower than the exact recalling of the results. In addition, those who made a mistake in the follow-up were inclined to have an optimistic view. Therefore, comprehensive health care for precise recalling of the results of medical checkups should be required to improve abnormal findings or maintain a good health status.

Adult↗
PubMed1996

Mobilization of peripheral blood progenitor cells following CHOP treatment combined with delayed granulocyte colony-stimulating factor administration in patients with non-Hodgkin's lymphoma.

The kinetic change in peripheral blood progenitor cells (PBPC) during 3 to 6 cycles of standard CHOP regimen supported with human recombinant granulocyte colony-stimulating factor (rG-CSF) was investigated in three patients with newly diagnosed intermediate grade, diffuse large cell type, non-Hodgkin's lymphoma (NHL) without bone marrow invasion. Patients were given rG-CSF subcutaneously (2 mu g/kg/day) initiated when total leukocytes was < 3.0 x 10(9)/1. When the leukocyte count remained at >3.0 x 10(9)/1, rG-CSF was started 10 days following the prior CHOP. Treatment with rG-CSF was discontinued after the leukocyte count reached >10.0 x 10(9)/1, and CHOP was started the next day (CHOP-G regimen). The number of PBPC was monitored by clonal assay in patients 1-3. No severe leukopenia with <0.5 x 10(9)/1 of neutrophils was seen in any patient. Colony-forming unit granulocyte-macrophage (CFU-GM) significantly increased after 2-3 days of consecutive administration of rG-CSF. The magnitudes of maximum amplification of CFU-GM in patients 1, 2, and 3, were 56-fold (during 3 cycles of CHOP-G), 216-fold (during 2 cycles), and 67-fold (during 4 cycles), respectively, and the absolute numbers of the maximum CFU-GM/ml blood were 983, 7,568, 9,865, respectively. In one patient who was given 6 cycles of CHOP-G, the peak values of mobilized CFU-GM in each cycle did not substantially decrease until 6 cycles of CHOP-G had been completed. Thus, the CHOP-G regimen described here seems to be very efficient increasing the circulating CFU-GM prior to harvesting PBPC.

Adolescent↗