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H Nomiyama

Publications and source records attributed to H Nomiyama.

At least 55 records · Page 3Linked to original sources
PubMed1997

Human monocyte chemotactic protein-2: cDNA cloning and regulated expression of mRNA in mesenchymal cells.

Stimulated MG-63 osteosarcoma cells have been used as a source to purify and identify the monocyte chemokines MCP-1, MCP-2 and MCP-3. In comparison with MCP-1, the production yields of MCP-2 and MCP-3 in these cells are rather low and variable. Although the protein sequence of human MCP-2 is identified, its DNA sequence remains elusive. A degenerate primer set was used to isolate an MCP-2 gene fragment from the chemokine YAC contig on human chromosome 17. Based on the gene sequence of MCP-2, a unique primer set was synthesized and used to screen cDNA libraries for the presence of MCP-2 transcripts by PCR. The complete MCP-2 cDNA was cloned from a human bone marrow cDNA library and sequenced. The cDNA-derived protein sequence was identical to that of purified natural MCP-2, except for Gln46 which replaced Lys46. There seem thus to exist two MCP-2 allelic variants because at position 46 the codons of two residues (Lys46 and Gln46) were detected in individual genomes. As shown by Northern hybridization, the MCP-2 steady-state mRNA levels in normal diploid fibroblasts were increased by IL-1 beta, IFN-gamma and the double-stranded RNA poly rI:rC. RT-PCR analysis showed induction of MCP-2 mRNA in MG-63 cells by IFN-gamma and IL-1 beta. The regulated production of MCP-2 by tumor cells and normal mesenchymal cells is indicative of a role in neoplasia and inflammatory host responses.

Amino Acid Sequence↗
PubMed1997

Novel lymphocyte-specific CC chemokines and their receptors.

By using a cloning method termed the signal sequence trap as well as by searching for chemokine homologous sequences in the database of expressed sequence tags, cDNA fragments potentially encoding novel CC chemokines were initially identified. Using these sequences, we have cloned five novel human CC chemokines termed TARC, LARC, ELC, SLC, and PARC. These chemokines are constitutively expressed especially in some lymphoid tissues with individually unique expression patterns. The recombinant proteins are all found to be selectively chemotactic for lymphocytes but not for monocytes or neutrophils. Each chemokine appears to interact with a class of receptors on lymphocytes that is not shared by any other chemokines so far tested. Furthermore, we have identified CCR4 as the specific receptor for TARC, GPR-CY4/DRY6/CKR-L3/STRL22 as that for LARC (CCR6), and EBI1/BLR2 as that for ELC (CCR7). Only the gene for PARC is mapped to the traditional CC chemokine gene cluster at chromosome 17q11.2, whereas those for TARC, LARC, ELC, and SLC are localized at different loci. Collectively, these five CC chemokines may constitute a new category of CC chemokines that are involved in trafficking and homing of particular subsets of lymphocytes in particular lymphoid tissue microenvironments.

Amino Acid Sequence↗
PubMed1997

The effect of wedged insoles on the thrust of osteoarthritic knees.

We describe a method of quantifying the lateral/medial thrust of the knee which occurs in the early phase of walking. We have used this method to evaluate the effects of wedged insoles on the lateral and medial thrust for normal knees and knees with unicompartment osteoarthritis (OA). A laterally elevated (valgus) insole decreased the lateral thrust of both normal and osteoarthritic knees. A medially elevated (varus) insole increased the lateral thrust. In 50 symptomatic knees with medial compartment OA, decreasing the lateral thrust with a valgus insole reduced pain on walking in 27. Patients whose pain was reduced by valgus insoles tended to have earlier OA and to have a significantly greater reduction in the lateral thrust than in the 23 remaining unaffected knees. A varus insole was effective in decreasing the medial thrust and reducing pain in all ten knees with lateral compartment OA. We recommend the use of valgus insoles for patients with painful early medial compartment OA and the use of varus insoles for lateral compartment OA.

Acceleration↗
PubMed1997

Structural and functional analysis of the promoter region of the human MCP-3 gene: transactivation of expression by novel recognition sequences adjacent to the transcription initiation site.

Human monocyte chemotactic factor-3 (MCP-3) belongs to the C-C chemokines, which are cytokines involved in cell recruitment in inflammation and cancer. Northern blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses showed that the MCP-3 gene is expressed in many human tissues and tumor cell lines and that the expression level is increased by various stimuli. Measles virus and phorbol 12-myristate 13-acetate (PMA) induced MCP-3 mRNA after 6 hr of stimulation. Interferon-beta (IFN-beta) induced MCP-3 mRNA after 16 hr, a time point when the PMA-induced mRNA had the tendency to level off. No significant increase in MCP-3 mRNA levels was observed in MG-63 cells after stimulation with interleukin-1beta (IL-1beta). To elucidate the regulation of MCP-3 gene expression, we determined the sequence of 5 kb of the MCP-3 promoter. This sequence contained a microsatellite that was shown to be polymorphic in various cell lines. Next 5'-deletion mutants of the promoter were generated and transfected into MG-63 cells, demonstrating the presence of several positive and negative transcriptional regulatory elements. One of the positive elements was located at -37, only 21 bp upstream from the TATAA box. This element was similar to an AP-1 element and also to a homeodomain protein Pbx1 binding site. A deletion mutant from -110 to +52 possessed the highest promoter activity, and the longer deletion mutants had relatively low activities. The region between -190 and -172 contained an Ets-like element and inhibited promoter activity. Stimulation with PMA dramatically increased promoter activity through activation of a positive element present between -172 and -100. The same 5'-deletion mutants were transfected into HeLa and Jurkat cells. None of the deletion mutants had any significant activity in Jurkat cells. In HeLa cells, low levels of MCP-3 mRNA were detected by RT-PCR, but the profile of the promoter activities of the deletion mutants was different from that seen in MG-63 cells.

Base Sequence↗
PubMed1997

Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.

Human macrophage inflammatory protein-1 alpha (hMIP-1 alpha), also known as LD78, is a member of the chemokine/ intercrine family and an inhibitor of the proliferation of the hematopoietic stem cells in vitro. Using a specific monoclonal antibody, we observed significant localization of hMIP-1 alpha in eosinophilic myelocytes in human bone marrow. We further examined the expression of hMIP-1 alpha mRNA in human bone tissue by in situ hybridization. A high level of hMIP-1 alpha mRNA expression was detected in eosinophilic myelocytes in bone marrow, confirming these cells as the site of hMIP-1 alpha synthesis. hMIP-1 alpha mRNA expression was also detected in osteoblasts in the bone-remodeling sites, and osteoclasts were frequently observed in the vicinity of these osteoblasts. hMIP-1 alpha was also able to induce osteoclastogenesis on calcified matrices in the absence of any other osteotropic hormones. These results strongly suggest that hMIP-1 alpha is involved not only in the regulation of hematopoiesis but also in the modulation of bone remodeling.

Animals↗
PubMed1996

A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2.

CC chemokines are cytokines that attract and activate leukocytes. The human genes for the CC chemokines are clustered on chromosome 17. To elucidate the genomic organization of the CC chemokine genes, we constructed a YAC contig comprising 34 clones. The contig was shown to contain all 10 CC chemokine genes reported so far, except for one gene whose nucleotide sequence is not available. The contig also contains 4 CC chemokine-like genes, which were deposited in GenBank as ESTs and are here referred to as NCC-1, NCC-2, NCC-3, and NCC-4. Within the contig, the CC chemokine genes were localized in two regions. In addition, the CC chemokine genes were more precisely mapped on chromosome 17q11.2 using a somatic cell hybrid cell DNA panel containing various portions of human chromosome 17. Interestingly, a reciprocal translocation t(Y;17) breakpoint, contained in the hybrid cell line Y1741, lay between the two chromosome 17 chemokine gene regions covered by our YAC contig. From these results, the order and the orientation of CC chemokine genes on chromosome 17 were determined as follows: centromere-neurofibromatosis 1-(MCP-3, MCP-1, NCC-1, I-309)-Y1741 breakpoint-RANTES-(LD78gamma, AT744.2, LD78beta)-(NCC-3, NCC-2, AT744.1, LD78alpha)-NCC-4-retinoic acid receptor alpha- telomere.

Animals↗
PubMed1996

Comparison between males and females with respect to the porphyrin metabolic disorders found in workers occupationally exposed to lead.

To elucidate the sex difference in porphyrin metabolic disorders induced by lead exposure, we determined plasma delta-aminolevulinic acid (ALA), urinary ALA, and urinary coproporphyrin (CP) in 298 lead-exposed workers (160 males and 138 females), and compared the data thus obtained. The use of fluorometric high-performance liquid chromatography (HPLC) method which is highly sensitive and specific made possible the measurement of ALA in a small volume (50 microliters) of plasma. The concentrations (mean +/- SD) of lead in blood (males: 55.1 +/- 12.9 micrograms/dl; females: 54.7 +/- 13.5 micrograms/dl) indicated that the intensity of occupational exposure to lead was almost equal in the two groups. However, the elevation of plasma ALA concentration and the increased urine ALA and CP excretion among these lead workers were much higher in females than in males, confirming the finding of a sex difference in the biological effect of human exposure. The difference in urine CP excretion was especially pronounced, the mean concentration of urinary CP in the female workers being 3.5-5 times higher than that in the male workers.

Adult↗
PubMed1995

Autonomic and central nervous system effects of lead in female glass workers in China.

To clarify the effects of lead on autonomic and central nervous system functions, electrocardiographic R-R interval variability (CVRR) as well as visual and brainstem auditory evoked potentials (VEP and BAEP) were measured in 36 female workers exposed to lead (exposed group) and in 15 female textile workers (unexposed group). The C-CVLF, C-CVHF (two component CVs of the CVRR reflecting sympathetic and parasympathetic activities, respectively), and LF/HF ratio (indicator of sympatho-vagal balance) were also computed from component spectral powers by means of autoregressive spectral and component analyses. The exposed group had engaged in glass work for 2-17 (mean 7.8) years. Blood lead (BPb) concentrations were 25.8-79.3 (mean 55.6) micrograms/dl in the exposed group and 4.7-8.6 (mean 6.3) micrograms/dl in the unexposed group. The CVRR, C-CVLF, C-CVHF, and LF/HF ratio in the exposed group were significantly lower than those in the unexposed group. Also, the exposed group had more complaints of subjective symptoms and signs than did the unexposed group. On the other hand, no significant differences in either VEP or BAEP latencies were found between the two groups. It is suggested that autonomic nervous function is more susceptible to lead than visual and auditory nervous functions; lead affects sympathetic activity more strongly than parasympathetic activity.

Adult↗
PubMed1995

[Cadmium].

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Cadmium↗
PubMed1994

A nine-year chronic toxicity study of cadmium in monkeys. II. Effects of dietary cadmium on circulatory function, plasma cholesterol and triglyceride.

The effects of long-term (9 y) po administration of daily low doses of cadmium on blood pressure, heart rate, electrocardiogram and plasma cholesterol and triglyceride concentrations were examined in rhesus monkeys. Thirty-five male rhesus monkeys were divided into 5 groups and fed pelleted food containing cadmium chloride at dosages of 0, 3, 10, 30 or 100 micrograms cadmium/g food (= ppm). The 100 ppm group had increased blood pressure during the initial 1 1/2 y. Thereafter, the expected increase in blood pressure that occurred due to aging in the control and 3 ppm groups was not evident in the 100 ppm group. No changes attributable to cadmium were detected in pulse rates or in electrocardiograms. Plasma cholesterol in the 2 highest dosage groups and triglyceride in the 100 ppm group were slightly lower than in controls after 2 1/2 y. Long-term exposure to cadmium contributed to the development of elevated blood pressure during the first and second years and then inhibited the hypertension expected due to aging.

Animals↗
PubMed1994

A nine-year chronic toxicity study of cadmium ingestion in monkeys. I. Effects of dietary cadmium on the general health of monkeys.

Thirty-five male rhesus monkeys (Macaca mulatta) 2-5 y-of-age were separated into 5 groups and fed 200 g solid food daily which contained 0, 3, 10, 30 or 100 micrograms cadmium/g (ppm) as cadmium chloride for 462 w (9 y). The control feed (0 ppm) contained 0.27 micrograms cadmium/g. Dietary zinc intake was limited to the minimum requirement of 6 mg zinc/day (control food concentration was 3 mg zinc/100 g) to avoid impacting cadmium toxicity due to excessive zinc intake. Urine was collected at 3-w intervals. Decreased development (reduced body weight and body length) was observed in groups that received 10 ppm cadmium or more. The 100 ppm group had glucose in the urine after 48 w, elevated urine protein at 98 w, and markedly increased urine volume after the 102nd week. No abnormalities in renal functions were noted in the 3 or 10 ppm groups. Despite the development of these clinical signs of renal dysfunction, none of the 100 ppm group had aggravated renal dysfunction or renal failure during the 9 y of study.

Animals↗
PubMed1993

Characterization of cytokine LD78 gene promoters: positive and negative transcriptional factors bind to a negative regulatory element common to LD78, interleukin-3, and granulocyte-macrophage colony-stimulating factor gene promoters.

Cytokine LD78 is a human counterpart of the mouse macrophage inflammatory protein 1 alpha/hematopoietic stem cell inhibitor. Promoters of the LD78 alpha and LD78 beta genes showed similar inducible activities in two leukemic cell lines, K562 and Jurkat, but the induction mechanisms differed between the two cell lines. Further characterization of the LD78 alpha promoter indicated that multiple positive and negative regulatory elements are present, some of which are differentially required for induction and repression of the promoter activity in different cells. One of the negative regulatory elements, ICK-1, functioned in both cell lines in the absence and presence of stimulation and was shown to be a recognition site for positive and negative transcriptional factors. This ICK-1 element contained a direct repeat, and similar repeats were also found in the negative regulatory elements of hematopoietic growth factor interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoters. Nuclear extracts from K562 and Jurkat cells formed several protein-DNA complexes with the LD78 alpha ICK-1 element, one of which was also observed with the IL-3 and GM-CSF ICK-1 elements. Results from in vivo and in vitro analyses suggested that the protein forming this complex functions as a negative factor. The binding affinity of this protein, ICK-1A, to the LD78 alpha ICK-1 element was low and was significantly affected by the incubation temperature and the salt concentration in the binding buffer. ICK-1B, another protein bound specifically by the LD78 alpha ICK-1 element, was shown to be a positive factor important for induction of the promoter. These results suggested that ICK-1A plays an important role in balanced expression of LD78, IL-3, and GM-CSF during hematopoietic cell growth and differentiation.

Animals↗
PubMed1993

T-cell chemotactic activity of cytokine LD78: a comparative study with interleukin-8, a chemotactic factor for the T-cell CD45RA+ phenotype.

The recombinant LD78 cytokine (rLD78) promoted migration of human peripheral T lymphocytes at concentrations from 10(-11) M to 10(-7) M, with a peak of activity at 10(-8) M. There was no difference in migration promoting activity between LD78 alpha and its variant LD78 beta. Checkerboard analysis indicated that the migration of T cells attracted by rLD78 was chemotaxis but not chemokinesis. The chemotactic activity of rLD78 was apparently ten-fold lower than that of recombinant inteleukin-8 (rIL-8) when peripheral T cells were used as the indicator cells. Subset analysis on T cells responding to rLD78 or rIL-8 indicated that rIL-8 was more chemotactic for the CD45RA+ T cell subset than the CD45RO+ subset, but did not distinguish between CD4+ and CD8+ T cell subsets. In contrast, rLD78 apparently distinguished neither between CD4+ and CD8+ T cell subsets nor between CD45RA+ and CD45RO+ subsets.

Cell Movement↗
PubMed1992

Recombinant LD78 protein, a member of the small cytokine family, enhances osteoclast differentiation in rat bone marrow culture system.

Cytokine LD78 is a member of the small inducible protein family involved in cell growth, wound healing and inflammation. However, its exact function is not known. In this study, we demonstrated that recombinant LD78 alpha and its variant LD78 beta proteins stimulate osteoclast-like cell formation in rat bone marrow cultures in the presence of 1 alpha, 25-dihydroxyvitamin D3. This enhancing activity was independent of prostaglandin synthesis. This is the first report which describes the effect of proteins involved in the small inducible protein family on the differentiation of osteoclasts.

Animals↗
PubMed1992

Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17.

Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed.

Base Sequence↗
PubMed1992

Critical levels of blood and urinary cadmium, urinary beta 2-microglobulin and retinol-binding protein for monitoring cadmium health effects.

The critical levels for monitoring cadmium health effects in 358 workers engaged in ore crushing/roasting (cadmium concentration in the workplace air 2.5-6.5 mg/m3), dry smelting (10.8-23.3 mg/m3), cadmium melting (0.01-0.16 mg/m3), and ingot making (2.8-4.7 mg/m3), were investigated. Exposure parameters such as blood and urinary cadmium were determined, together with biological parameters such as proteinuria, amino acids, glucose, beta 2-microglobulin, retinol-binding protein, albumin, plasma beta 2-microglobulin, creatinine clearance, tubular reabsorption of beta 2-microglobulin and phosphate, and blood and urinary levels of zinc, copper and lead. Factor analysis and stepwise regression analysis were then applied to the data to classify parameters and to find the main contributing parameter. Blood and urinary cadmium, urinary beta 2-microglobulin, retinol-binding protein and the ratio of urinary beta 2-microglobulin to albumin were also subjected to multiple correlation analysis, multiple regression analysis and the Chi-square test was applied to contingency tables. It is concluded, based on the data, that cadmium health effects may be assessed by using the following critical levels: blood cadmium: 10 micrograms/l, urinary cadmium: 10 micrograms/g creatinine; urinary beta 2-microglobulin: 2000 micrograms/g creatinine, urinary retinol-binding protein: 200 micrograms/g creatinine and a ratio of urinary beta 2-microglobulin to albumin of 0.001.

Adult↗