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Biomedical subjects

M Hagiya

Publications and source records attributed to M Hagiya.

At least 19 recordsLinked to original sources
PubMed2000

Molecular computation by DNA hairpin formation.

Hairpin formation by single-stranded DNA molecules was exploited in a DNA-based computation in order to explore the feasibility of autonomous molecular computing. An instance of the satisfiability problem, a famous hard combinatorial problem, was solved by using molecular biology techniques. The satisfiability of a given Boolean formula was examined autonomously, on the basis of hairpin formation by the molecules that represent the formula. This computation algorithm can test several clauses in the given formula simultaneously, which could reduce the number of laboratory steps required for computation.

Algorithms↗
PubMed2000

Augmenter of liver regeneration (ALR) may promote liver regeneration by reducing natural killer (NK) cell activity in human liver diseases.

Cytotoxicity of liver natural killer cells against regenerating hepatocytes has been reported as a possible mechanism of regeneration failure in fulminant hepatitis. An augmenter of liver regeneration (ALR) inhibits liver natural killer cell activity in rats. In this study, we measured hepatic expression of ALR mRNA, blood levels of ALR, and peripheral blood natural killer cell activity in patients with various types of acute liver disease to investigate the relationship between failure of liver regeneration and hepatic natural killer cells. Hepatic ALR mRNA expression was higher in liver disease patients than in non-liver disease controls, and a correlation was found between serum ALR values and hepatic levels of ALR mRNA. In acute liver injury, the serum ALR level also showed a negative correlation with NK activity. ALR was produced by and released from the liver at the time of hepatic injury. Our findings suggest that ALR may protect against failure of regeneration by inhibition of hepatic natural killer cell activity in acute liver injury.

Antibodies↗
PubMed1999

Characterization of free alpha- and beta-chains of recombinant macrophage-stimulating protein.

Human serum macrophage-stimulating protein (MSP) induces motile activity of murine resident peritoneal macrophages and is a growth and motility factor for epithelial cells. It belongs to the plasminogen-related family of kringle proteins, and is secreted as a single-chain, 78-kDa, biologically inactive pro-MSP. Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. However cleavage of recombinant pro-MSP yielded not only the disulfide-linked heterodimer, but also free alpha- and beta-chains, indicating that some of the recombinant molecules lacked an alphabeta-chain disulfide. We purified the free chains for characterization. The beta-chain of MSP has three extra cysteines, Cys527, Cys562, and Cys672, which are not found in the plasminogen beta-chain. Disulfide bond analysis showed a Cys527-Cys562, but also a Cys588-Cys672. Coopting Cys588 by Cys672 prevented the expected formation of a disulfide between alpha-chain Cys468 and beta-chain Cys588. Concomitant studies determined structures of oligosaccharides at the three Asn-linked glycosylation sites of MSP. The oligosaccharides at the three Asn loci are heterogeneous; 11 different sugars were identified, all being sialylated fucosyl biantennary structures. We also located the pro-MSP signal peptide cleavage site at Gly18-Gln19 and the scissile bond for formation of mature MSP at Arg483-Val484.

Amino Acids↗
PubMed1999

State transitions by molecules.

In our previous paper, we described a method by which a state machine is implemented by a single-stranded DNA molecule whose 3'-end sequence encodes the current state of the machine. Successive state transitions are performed in such a way that the current state is annealed onto an appropriate portion of DNA encoding the transition table of the state machine and the next state is copied to the 3'-end by extension with polymerase. In this paper, we first show that combined with parallel overlap assembly, a single series of successive transitions can solve NP-complete problems. This means that the number of necessary laboratory steps is independent from the problem size. We then report the results of two experiments concerning the implementation of our method. One is on isothermal reactions which greatly increase the efficiency of state transitions compared with reactions controlled by thermal cycles. The other is on the use of unnatural bases for avoiding out-of-frame annealing. The latter result can also be applied to many DNA-based computing paradigms.

Animals↗
PubMed1999

[Alpha 1-antitrypsin deficiency (Siiyama) with pulmonary emphysema].

A 44-year-old man was admitted to the hospital with dyspnea on exertion. Chest radiographs and pulmonary function tests showed evidence of pulmonary emphysema. Serum alpha 1-antitrypsin (alpha 1-AT) could not be detected by nephelometry, immuno-electrophoresis, or iso-electric focusing. However, allele-specific PCR revealed a genotype homozygotic for an alpha 1-AT deficient variant of the Siiyama allele. An elder sister of the proband was also a homozygous carrier of the Siiyama allele. The amino acid sequence for normal alpha 1-AT variants had been substituted by Arg101-Val213-Glu376 in the proband, demonstrating that the alpha 1-antitrypsin-deficient Siiyama variant in this pedigree was derived from M 1 (Val213).

Adult↗
PubMed1998

[Factors contributing to an increase in DLco (steady state) after exercise in healthy men].

We studied factors contributing to an increase of DLco (steady state) from rest to exercise in 10 healthy men. DLco(ss), Dm, and Vc were measured under three different conditions, rest, constant load exercise (50 watts), and hyperventilation (equal to the tidal volume and respiratory rate of exercise). DLco(ss) increased significantly during exercise and hyperventilation compared with at rest. DLco(ss) also increased significantly during exercise, compared with hyperventilation. During constant load exercise (50 watts) increased Dm and Vc, caused by increased ventilation, together with increased of Vc caused by increased of pulmonary blood flow resulted in an increase in DLco(ss).

Adult↗
PubMed1998

[One year follow-up of pulmonary rehabilitation in patients with pulmonary emphysema--physiological outcome].

To evaluate the long-term effects of pulmonary rehabilitation on physiological outcome, 12 patients with pulmonary emphysema were enrolled in an inpatient pulmonary rehabilitation program for 6 weeks. After discharge from the hospital, they were followed up for 1 year. The pulmonary rehabilitation program consisted of breathing retraining, thoracic mobilization, exercise training, and patient education. Although the subjects did not participate in outpatient maintenance group sessions after their discharge, they continued breathing retraining and exercise training at home. Their vital capacity improved significantly, and was sustained over the course of the year; other pulmonary functions, however, did not change significantly. Maximum exercise load increased 31% after the rehabilitation program; although it was 18% higher than baseline at follow-up one year later, that was not a significant change. The follow-up data on exercise traming had generally deteriorated 1 year after the rehabilitation program. The change in maximum exercise load from baseline before and after the inpatient pulmonary rehabilitation program correlated closely with the change in maximum exercise load thereafter to follow-up one year later (R = 0.62). We conclude that it is pessible to estimate long-term change in exercise capacity on the basis of short-term changes achieved during inpatient pulmonary rehabilitation. It may be necessary to develop maintenance programs of some kind to help pulmonary emphysema patients retain the benefits of pulmonary rehabilitation over the longer term.

Aged↗
PubMed1997

Cloning, expression, and characterization of a cDNA encoding a novel human growth factor for primitive hematopoietic progenitor cells.

Multiple growth factors synergistically stimulate proliferation of primitive hematopoietic progenitor cells. A human myeloid cell line, KPB-M15, constitutively produces a novel hematopoietic cytokine, termed stem cell growth factor (SCGF), possessing species-specific proliferative activities. Here we report the molecular cloning, expression, and characterization of a cDNA encoding human SCGF using a newly developed lambdaSHDM vector that is more efficient for differential and expression cloning. cDNA for SCGF encodes a 29-kDa polypeptide without N-linked glycosylation. SCGF transiently produced by COS-1 cells supports growth of hematopoietic progenitor cells through a short-term liquid culture of bone marrow cells and exhibits promoting activities on erythroid and granulocyte/macrophage progenitor cells in primary semisolid culture with erythropoietin and granulocyte/macrophage colony-stimulating factor, respectively. Expression of SCGF mRNA is restricted to myeloid cells and fibroblasts, suggesting that SCGF is a growth factor functioning within the hematopoietic microenvironment. SCGF could disclose some human-specific mechanisms as yet unidentified from studies on the murine hematopoietic system.

Amino Acid Sequence↗
PubMed1997

Macrophage stimulating protein (MSP) binds to its receptor via the MSP beta chain.

Macrophage stimulating protein (MSP) is a 78-kDa disulfide-linked heterodimer belonging to the plasminogen-related kringle protein family. MSP activates the RON receptor protein-tyrosine kinase, which results in cell migration, shape change, or proliferation. A structure-activity study of MSP was performed using pro-MSP, MSP, MSP alpha and beta chains, and a complex including the first two kringles and IgG Fc (MSP-NK2). Radioiodinated MSP and MSP beta chain both bound specifically to RON. The Kd of 1.4 nM for MSP beta chain is higher than the reported Kd range of 0.6-0.8 nM for MSP. Pro-MSP, MSP alpha chain, and MSP-NK2 did not bind. Only MSP stimulated RON autophosphorylation. Although the beta chain bound to RON and partially inhibited MSP-induced RON phosphorylation in kidney 293 cells, it did not induce RON phosphorylation. Pro-MSP, MSP alpha chain, or MSP-NK2 failed to activate RON, consistent with their inability to bind to the RON receptor. Functional studies showed that only MSP induced cell migration, and shape change in resident macrophages, and growth of murine keratinocytes. Our data indicate that the primary receptor binding domain is located in a region of the MSP beta chain, in contrast to structurally similar hepatocyte growth factor, in which the receptor binding site is in the alpha chain. However, full activation of RON requires binding of the complete MSP disulfide-linked alphabeta chain heterodimer.

3T3 Cells↗
PubMed1997

Crystallization and preliminary crystallographic data for the augmenter of liver regeneration.

A new cellular growth factor termed augmenter of liver regeneration (ALR) has been crystallized. ALR has been shown to have a proliferative effect on liver cells while at the same time producing an immunosuppressive effect on liver-resident natural killer cells and liver-resident mononuclear leukocytes. In addition, ALR appears to play an important role in the synthesis and stabilization of mitochondrial gene transcripts in actively regenerating cells. ALR crystals diffract to beyond 2 A resolution and belong to space group P2(1)2(1)2, with a = 125.1, b = 108.1 and c = 38.5 A. Based on four molecules per asymmetric unit, the Matthews coefficient is calculated to be 2.16 A(3) Da(-1) which corresponds to a solvent content of 43%.

Journal Article↗
PubMed1997

The in vivo effect of hepatotrophic factors augmenter of liver regeneration, hepatocyte growth factor, and insulin-like growth factor-II on liver natural killer cell functions.

Fine balanced sequential changes of the levels of circulating hepatotrophic factors are essential for normal liver regeneration. Our recent studies have indicated that liver-resident natural killer (NK) cells are important regulators of liver regeneration and have raised the possibility that hepatotrophic factors might mediate their activities through NK cells. In the present study, we assessed the effects of in vivo administration of three hepatotrophic factors (augmenter of liver regeneration [ALR], insulin-like growth factor-II [IGF-II], and hepatocyte growth factor [HGF]) on NK cells in normal rats. Each of the three, given over a 1-day period in doses known to produce hepatotrophic activity, induced inhibition of NK cell cytotoxic activities in the population of mononuclear leukocytes (MNL) in the liver, but not in MNL from the spleen or peripheral blood. In contrast to these results obtained by the whole animal treatment, the three molecules had no effect on NK cell functions when added to cultures of MNL from the livers, spleens, or blood of untreated rats. These data support and extend our previously advanced hypothesis that ALR and other hepatotrophic factors play an important role in liver regeneration by regional regulation of NK cells through some as-yet-unknown intermediary mechanism.

Animals↗
PubMed1997

Effect of respiratory rate on respiratory patterns in patients with chronic obstructive pulmonary disease.

We enrolled 22 patients with chronic obstructive pulmonary disease (COPD) and 20 normal subjects as controls. Using a hot-wire flow meter, we obtained tidal volume (VT), duty ratio (Ti/Ttot), and mean inspiratory flow (VT/Ti) as measures of respiratory pattern at two different respiratory rates; 0.5 Hz and 1.5 Hz. At 0.5 Hz, there were significant differences in Ti/Ttot and VT/Ti. At 1.5 Hz, patients with COPD had significantly lower values of VT and VT/Ti. Furthermore, we calculated the change ratios from 0.5 Hz to 1.5 Hz in these parameters as new parameters of respiratory pattern change by respiratory rate. VT0.5/1.5 and VT/Ti0.5/1.5 significantly correlated with FEV1.0/FVC. The findings suggest that the parameters of the respiratory pattern may change depending on respiratory rates, and that the ratios of those parameters obtained at two different rates could be helpful in diagnosing airflow obstruction.

Aged↗
PubMed1997

[Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema].

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.

Aged↗
PubMed1996

Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene.

BACKGROUND: The gene encoding the hepatotrophic factor Augmenter of Liver Regeneration (ALR) has recently been cloned in the rat. The availability of the mouse form of ALR would allow the analysis of the role of this factor in the physiology of liver and other organs, while the identification of the human homolog would allow the transfer of the great wealth of information that has been generated in animal models to clinically oriented pilot trials, and eventually the therapeutic application of this information. MATERIALS AND METHODS: Standard molecular biology approaches have been used to determine the genomic structure of the ALR gene in the mouse, and to characterize the ALR transcript and its protein product. The human ALR cDNA was also isolated and the amino acid sequence of the human gene product deduced. The mapping of mouse and human ALR genes on mouse and human chromosomes was then completed. RESULTS: The protein coding portion of the mouse ALR gene is comprised of three exons, the first containing the 5' untranslated sequence and the initial 18 bases after the ATG translation initiation codon, the second exon encompasses 198 bases, and the third exon contains the remaining portion of the protein coding sequence. Rat, mouse, and human ALR genes (and protein products) were found to be highly conserved and preferentially expressed in the testis and in the liver. The ALR gene maps to the mouse chromosome 17, in a region syntenic with human chromosome 16, where the T/t region has also been mapped. CONCLUSIONS: ALR appears to be a protein with important physiologic properties, not exclusively limited to liver regeneration, with roles that are involved in the synthesis or stability of the nuclear and mitochondrial transcripts that are present in actively regenerating cells, particularly the germ cells of the testes.

Amino Acid Sequence↗
PubMed1996

[Effects of pulmonary rehabilitation on vital capacity in patients with chronic pulmonary emphysema].

To evaluate the effects of pulmonary rehabilitation on pulmonary function, 15 patients with chronic pulmonary emphysema underwent pulmonary rehabilitation for six weeks as inpatients. Pulmonary rehabilitation consisted of relaxation techniques, breathing retraining, thoracic massage, physical exercise, and walking. In 8 of the 15 patients vital capacity increased by more than 200 ml (over 10%), and in 7 of the 15 patients the load of maximal exercise increased by more than 5 watts (over 10%). Increases in vital capacity were not associated with increases in maximal exercise load. The percent change in vital capacity associated with pulmonary rehabilitation correlated significantly with the percent change in tidal volume and the percent change in expiratory minute ventilation at the maximal load. The percent change in tidal volume at the maximal load correlated significantly with the percent change in maximum oxygen uptake. We attribute the increase in vital capacity to an improvement in thoracic cage movement. These findings suggest that pulmonary rehabilitation can increase vital capacity in some patients with chronic pulmonary emphysema, and that such an increase is not directly connected to increases in exercise capacity.

Aged↗
PubMed1996

[Psychological and physiological changes accompanying pulmonary rehabilitation in patients with chronic pulmonary emphysema].

In 14 patients with chronic pulmonary emphysema, the relations between changes in psychological status associated with pulmonary rehabilitation and exercise tolerance were studied with the Cornell Medical Index and the Yatabe-Guiford Personality Inventory. Although the scores on the latter did not change, the cardio-respiratory score on the Cornell Medical Index improved significantly (p < 0.05). The only index of exercise tolerance that improved significantly was the distance walked in 10 minutes (p < 0.05). The changes in the scores of "Lack of Objectivity" and "Rhathymia" correlated negatively with the change in the distance walked in 10 minutes (R = -0.80, p < 0.01; R = -0.81, p < 0.01). The change in psychological status that accompanied pulmonary rehabilitation has been related to the improvement in the distance walked in 10 minutes.

Aged↗
PubMed1994

Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution.

A full-length cDNA clone encoding a purified augmenter of liver regeneration (ALR) factor prepared from the cytosol of weanling rat livers was isolated. The 1.2-kb cDNA included a 299-bp 5' untranslated region, a 375-bp coding region, and a 550-bp 3' untranslated region. It encoded a protein consisting of 125 amino acids. The molecular weight of ALR calculated from the cDNA was 15,081, which is consistent with the size estimated by SDS/PAGE under reducing conditions. The molecular weight of the purified native ALR estimated by SDS/PAGE under nonreducing conditions was approximately 30,000; thus ALR apparently has a homodimeric structure. The recombinant ALR produced by expression of the cDNA in COS cells was tested in vivo in the canine Eck fistula model and found to have potency equivalent to the purified native ALR. The 125-aa sequence deduced from the rat ALR cDNA shows 50% homology to the amino acid sequence of the gene for oxidative phosphorylation and vegetative growth in the yeast Saccharomyces cerevisiae.

Amino Acid Sequence↗