Biomedical subjects

M Maki

Publications and source records attributed to M Maki.

At least 19 recordsLinked to original sources

PubMed1995

Analysis of a novel defective HTLV-I provirus and detection of a new HTLV-I-induced cellular transcript.

HTLV-I generally integrates at least one full-length copy in adult T-cell leukemia (ATL) cells. A group of patients without full-length provirus have a unique conserved truncation of the provirus which retains env-pX-3'LTR. Tumor cells of a patient from this group were genetically analyzed. Analysis of the 5' and 3' cellular flanking region adjacent to the provirus suggest that the defective provirus was integrated immediately downstream of a promoter of an unknown cellular gene. The activity of the promoter was weak but was responsive to Tax-like HTLV-I LTR. The provirus may have utilized it as a substitute for the 5'LTR and thus 3'LTR may have become an alternative promoter for the cellular gene, which may give similar viral-cellular interactions to that of general cases with full-length proviruses. Surprisingly, the 3' cellular flanking region which is thought to be controlled originally by the promoter is constitutively expressed specifically in an HTLV-I producing ATL cell line HUT1O2G, in which the corresponding region is not modified by provirus. The detection of this HTLV-I-induced transcript provides a probe to find an HTLV-I inducible unknown cellular gene that may be related to the pathogenesis of ATL.

Adult↗

PubMed1995

Purification of mu-calpain by a novel affinity chromatography approach. New insights into the mechanism of the interaction of the protease with targets.

A calmodulin-binding motif is a common structural feature of a number of calpain substrates (1). Since a calmodulin-like domain has been identified in both subunits of the calpain molecule, the proposal was made that the domain(s) would recognize the calmodulin-binding motifs of the substrates prior to the enzymatic modification by calpain. In keeping with the proposal, a successful attempt to purify mu-calpain from human erythrocytes was made by using an affinity chromatography approach in which the synthetic peptide C49, containing the calmodulin-binding domain of the plasma membrane Ca(2+)-ATPase, was coupled to a Sepharose matrix. The calmodulin-like domain of the catalytic subunit of human mu-calpain expressed in Escherichia coli was also retained by the C49-Sepharose column. Both mu-calpain and the calmodulin-like domain interacted with C49 in a Ca(2+)-dependent way and were eluted from the column by Ca(2+)-chelating agents. The finding confirmed the interaction between the calmodulin-binding domain of the plasma membrane Ca(2+)-ATPase and the calmodulin-like domain of mu-calpain. Experiments were performed to establish whether irreversibly inactivated mu-calpain or its expressed C-terminal portion containing the calmodulin-like domain could activate the hydrolysis of ATP by the plasma membrane Ca2+ pump, in keeping with evident ATPase stimulation of the same pump by calmodulin. A stimulation was observed, but it was much weaker than that induced by calmodulin.

Amino Acid Sequence↗

PubMed1995

Preference of calcium-dependent interactions between calmodulin-like domains of calpain and calpastatin subdomains.

Calpastatin molecule contains four repeated inhibition domains, each having highly conserved internal regions A, B and C. The synthetic oligopeptides of regions A and C had no calpain inhibition activity while region B oligopeptide showed weak inhibition activity. Real-time biomolecular interaction analysis using a BIAcore instrument revealed that the bacterially expressed calmodulin-like domain of the calpain large subunit (L-CaMLD) and that of the small subunit (S-CaMLD) interacted, in a Ca(2+)-dependent fashion, preferentially with the immobilized synthetic oligopeptide of region A and that of region C, respectively. Calmodulin showed no specific binding to these oligopeptides. The tripartite structure of the calpastatin functional domain may confer the specific interactions with the protease domain and the two CaMLDs of calpain.

Amino Acid Sequence↗

PubMed1995

Suppression of calphobindin I (CPB I) production in carcinoma of uterine cervix and endometrium.

Calphobindin I (CPB I) is a member of the family of Ca(2+)-dependent phospholipid binding proteins collectively termed as annexins. CPB I (Annexin V) has recently been shown to be an endogenous inhibitor of protein kinase C, a key enzyme in the cellular signal transduction and its inhibition by CPB I is presumed to be related ultimately to carcinogenesis. We therefore examined the level of production of CPB I in uterine cancer cells. Immunohistochemical analysis, northern blot, and in situ hybridization showed that the production of CPB I was markedly suppressed at the level of transcription in both cervical and endometrial carcinoma cells when compared to their normal counterparts. Decrease in production of CPB I may lead to dysregulated activation of protein kinase C and, accordingly, may be involved in a disorder of cell differentiation, proliferation, and carcinogenesis.

Annexin A5↗

PubMed1995

Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy.

Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells. An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells. The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev did not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell. We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Somatostatinoma of the pancreas associated with von Hippel-Lindau disease.

A 39-year-old man was admitted because of lumbago, vomiting and massive gastrointestinal bleeding. Oliguria developed a few days later, which was followed by hyperkalemia and cardiac arrest. Autopsy disclosed multiple renal cell carcinomas with diffuse metastasis to the liver, adrenal gland, psoas muscle and vertebrae. In addition, a somatostatinoma was found in the pancreas. From these findings and past history of cerebellar hemangioblastoma and spinal hemangioma he was diagnosed to have von Hippel-Lindau disease. Von Hippel-Lindau disease with islet cell tumor is very rare and is reported here with a review of literature.

Adult↗

PubMed1995

[Two cases of dilated cardiomyopathy with the relationship between the effect of beta-blocker therapy and the changes of myocardial clearance of 123I-metaiodobenzylguanidine].

Two cases diagnosed dilated cardiomyopathy received beta-blocker therapy, and underwent 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy before and after the treatment. In case 1, symptoms and cardiac function were improved in 1 month and 4 months after the treatment (LVEF increased from 19% to 32% and 40%), and myocardial clearance of MIBG decreased from 50% to 27% and 29%. In case 2, both symptoms and cardiac function were not improved in 1 month and 3 months after the treatment (LVEF was changed from 11% to 10% and 13%), and myocardial clearance was not significantly different between before (50%) and after (1 month: 46%, 3 months: 50%) the treatment. It was indicated that myocardial clearance of MIBG might depend on the extent of the improvement of cardiac function and symptoms, and might reflect the effects of beta-blocker therapy.

3-Iodobenzylguanidine↗

PubMed1994

Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B.

Activation of the NF-kappa B/Rel family of transcription factors is regulated by a cytoplasmic inhibitor, I kappa B alpha. Activity of I kappa B alpha is in turn modulated by phosphorylation and proteolysis. It has been postulated that phosphorylation of I kappa B alpha leads to its dissociation from NF-kappa B, and free I kappa B alpha is targeted for rapid degradation. However, this phosphorylation-mediated dissociation event has not been demonstrated in vivo. We demonstrate that, contrary to this hypothesis, phosphorylation of I kappa B alpha induced by tumor necrosis factor alpha in HeLa cells does not induce dissociation. We propose a model in which (i) induced phosphorylation of I kappa B alpha does not result in its dissociation from NF-kappa B, (ii) phosphorylation of I kappa B alpha serves as a signal for degradation, and (iii) degradation of I kappa B alpha occurs while it is still complexed with NF-kappa B.

Calpain↗

PubMed1994

[Therapeutic effectiveness of 131I-MIBG on malignant pheochromocytoma--results of long-term follow-up].

The therapeutic response of 131I-MIBG was evaluated in 4 patients with malignant pheochromocytoma who had been treated with 131I-MIBG and followed-up over 5 years. The patients were 2 men and 2 women with ages ranging from 41 to 69 years old (mean 53 years). The primary tumors in 3 of 4 patients had been resected four to eight years before 131I-MIBG treatment. One patient was diagnosed as adrenal pheochromocytoma, and two were retroperitoneal paraganglioma. And in one patient, the resection of primary mediastinal tumor was not performed due to the adhesion to pericardium but the diagnosis of paraganglioma was obtained by biopsy of bone lesion. All patients showed the clear accumulation of 131I-MIBG in tumor on scintigraphy. The number of doses of 131I-MIBG ranged from one to three times with 3.7 GBq per administration and a cumulative activity from 3.7 to 11.1 GBq. Treatment effect was obvious in one patient with lung, bone, and lymph node metastases whose cumulated absorbed dose with 11.1 GBq of 131I-MIBG exceeded over 150 Gy. At the present time, the duration of survival since the beginning of initial 131I-MIBG therapy is over 5 yrs. The other three patients, however, showed little effects, and died with the disease in 2.6 to 4.1 years after the initial 131I-MIBG therapy. 131I-MIBG will become a promising agent for therapy in patients with malignant pheochromocytoma with high degree of accumulation.

3-Iodobenzylguanidine↗

PubMed1994

[Evaluation of myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP)].

To evaluate the myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), nineteen patients with ischemic heart disease including left ventricular hypertrophy (mean age 63 +/- 7.8, 14 males and 5 females) underwent BMIPP myocardial scintigraphy. Myocardial uptake (MU) of BMIPP to the total injected dose was calculated from anterior view of the planar image in all subjects, and was compared with plasma glucose (BS), triglyceride (TG), and free fatty acid (FFA). It was also compared with left ventricular mass (LVM) calculated with echocardiography. MU was not related to BS, TG, and FFA, however had the positive correlation with LVM (r = 0.676, p < 0.01). Myocardial uptake per left ventricular mass (MU/LVM) had the negative correlation with LVM (r = -0.671, p < 0.01). Further studies for the significance of MU/LVM will be required.

Aged↗

PubMed1992

Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I.

We examined the distribution of calpains I and II in human hematopoietic system cell lines by Western and Northern blot analyses and enzyme activity assay. Expression of calpain I, a low Ca(2+)-requiring cysteine protease, was observed in all human T-cell lines tested. By contrast, expression of calpain II, a high Ca(2+)-requiring form, in human T-cells was closely correlated with human T-cell leukemia virus type I (HTLV-I) infection, which is known to result in the expression of adult T-cell leukemia-associated antigens, interleukin-2 (IL-2) receptor alpha, and Ca(2+)-dependent cell proliferation. Specific expression of calpain II in HTLV-I-infected cells occurred at the mRNA level. Furthermore, expression of calpain II in human natural killer-like cells was augmented by HTLV-I pX gene transfection. In HTLV-I-infected cells, the trans-acting transcriptional activation of the long terminal repeat and control elements for the IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor genes by the Tax from the pX gene is already known. Our results suggest that the similar trans-activation occurs to the calpain II gene in HTLV-I-infected hematopoietic system cells.

Blotting, Western↗

PubMed1992

Transforming activity and the level of Tax protein: effect of one point mutation in HTLV-I tax gene.

The transcriptional trans-activator molecule of HTLV-I, Tax, is known to transform rodent fibroblasts. A revertant clone expressing Tax was obtained by treating transformed Rat-I cells harboring a single copy of the tax gene with a mutagen. Sequence analysis of the tax gene of the revertant clone revealed that it had one point mutation at codon 12(CTT----TTT), resulting in a change from Leu to Phe. The colony-forming efficiencies of the cells transfected with the mutant tax gene (mu71 tax) were significantly lower than those transfected with the wild-type by the soft-agar method. This difference was shown to be due to the instability of mu71 Tax.

Amino Acid Sequence↗

PubMed1992

Molecular diversity in amino-terminal domains of human calpastatin by exon skipping.

Calpastatin, a specific inhibitor of calpain, consists of a unique N-terminal domain (domain L) and four repetitive calpain-inhibition domains (domains 1-4). Calpastatin cDNA of human was reported to have two deletions in domains L and 1, as compared with that of pig and rabbit. We isolated human calpastatin genomic DNA clones, and the sequence analysis revealed seven exons for domain L and five exons for domain 1. Those deletions in the human cDNA were retained in its genomic DNA as exons 3 and 11. By the reverse transcription polymerase chain reaction method, three calpastatin cDNAs, full-length domains L and 1, and two natural mutants with deletions in either exon 3 or in both exons 3 and 5, were cloned from human fibroblast WI-38 cell line mRNA. Domain L was found to be rich in basic amino acid residues, especially for exon 3, and its N-terminal half was highly conserved among species. The isoelectric points (pI) of domain L and domains 1-4 were calculated to be 10.27 and 4.26-4.90, respectively. Moreover, human tissues and cell lines displayed different patterns of reverse transcription polymerase chain reaction products in agarose gel electrophoresis. Therefore, alternative splicing is most likely the cause for the molecular diversity, and the multiple isoforms are implicated for specific physiological roles.

Base Sequence↗

PubMed1992

Multiple forms of rat calpastatin cDNA in the coding region of functionally unknown amino-terminal domain.

Partial mouse and rat calpastatin cDNAs containing functionally unknown amino-terminal regions were cloned by the polymerase chain reaction (PCR) method. Two types of clones were obtained for the rat calpastatin; one had a sequence similar to mouse and human calpastatins, while the other had a deletion of 38 amino acid residues in this region. Both types of the rat sequence differed from the previously reported rat calpastatin which had additional deletions. The occurrence of multiple forms of calpastatin suggests alternative splicing in the functionally unknown domain.

Amino Acid Sequence↗

PubMed1992

The relation between amniotic fluid surfactant concentration in preterm labour and histological evidence of chorioamnionitis.

Concentration of amniotic fluid disaturated phosphatidylcholine (DSPC), factors related to cervical ripening, and histopathological evidence of chorioamnionitis were studied in 38 patients in preterm labour with intact membranes; all of them delivered spontaneously before 37 weeks. There was no correlation between the amniotic fluid DSPC level and gestational age at the time of amniocentesis. However, a significant inverse correlation was found between the amniotic fluid DSPC level and the interval between the onset of labour and delivery. The amniotic fluid DSPC level in cases with onset-delivery interval of less than 48 h was significantly higher than that in cases with an onset-delivery interval of 48 h or more. The gestational age in the former group was significantly lower than in the latter (28.6 vs 32.0 weeks). The amniotic fluid DSPC level in the patients with chorioamnionitis was significantly higher than that in the patients without chorioamnionitis, although the gestational age did not differ between the two groups. All 3 infants with RDS were associated with cervical incompetence. Patients in preterm labour with chorioamnionitis may be refractory to tocolysis and have higher amniotic fluid surfactant levels.

Adult↗

PubMed1992

Effects of danazol at the immunologic level in patients with adenomyosis, with special reference to autoantibodies: a multi-center cooperative study.

OBJECTIVE: We attempted to evaluate the effects of danazol on autoantibodies, in particular, to phospholipids, and on the immune system in patients with adenomyosis. STUDY DESIGN: Forty-two patients with adenomyosis who had high titers of autoantibodies were randomly chosen, and they received 400 mg/day of danazol for 4 months (n = 22) or underwent hysterectomy (n = 20). RESULTS: Among the six autoantibodies we investigated, the incidence of antiphosphatidylinositol immunoglobulin G was the highest (42.9%), followed by antiphosphatidylglycerol immunoglobulin G (38.1%). The autoantibody titers decreased with time and were comparable to the control values 16 weeks after treatment in both groups. Total serum levels of immunoglobulin G and M were high before treatment, but immunoglobulin M levels decreased significantly in week 8 during treatment with danazol, whereas C4 levels increased and C3 levels decreased with danazol. CONCLUSION: Danazol has an inhibitory effect on the autoimmunologic response associated with adenomyosis.

Autoantibodies↗

PubMed1992

A comparison of observed and self-reported compliance with universal precautions among emergency department personnel at a Minnesota public teaching hospital: implications for assessing infection control programs.

STUDY OBJECTIVES: To determine the level of universal precautions compliance in a hospital emergency department by two methods (direct observation of subjects versus self-reporting by questionnaire). SETTING: A Level II trauma center located within a university-affiliated medical center in Minneapolis/St Paul, Minnesota. Glove and needle disposal containers were available in each treatment room; gowns, masks, and goggles were readily available. PARTICIPANTS: ED physicians (12 staff plus rotating residents), medical students, nursing staff, and ancillary personnel. METHODS: Ten observers documented six specific behaviors among ED personnel: needle recap frequency, needle recap techniques, and use of gowns, gloves, masks, and goggles. After the observations, surveys were distributed to ED personnel by intrahospital mail in Fall 1989. RESULTS: During 270 observation hours, 1,018 patient-worker interactions were recorded. Gloves were the barrier worn most frequently when appropriate (74%), followed by goggles (13%), gowns (12%), and masks (1%). Needles were recapped 51% of the time, and most needles that were recapped (79%) were recapped by the two-hand technique; 5% of all needles used were left uncapped at bedside or in the trash. Physicians were observed to use gloves more frequently than registered nurses and nursing assistants; nurses were observed to recap more frequently than physicians. From the survey, the three most common reasons for noncompliance involved time (71%), dexterity (61%), and patient appearance (50%). CONCLUSION: Universal precautions are not consistently used by ED personnel, and ED personnel significantly overestimate their compliance with universal precautions.

Data Collection↗

PubMed1992

Calphobindins (placental annexins) inhibit protein kinase C.

Calphobindins (CPBs, placental annexins) are intracellular Ca(2+)- and phospholipid-dependent proteins like protein kinase C [EC 2.7.1.37]. We investigated the inhibitory effects of calphobindins on the protein kinase C activity in vitro. CPB I inhibited the protein kinase C activity for both histone phosphorylation and lipocortin phosphorylation, but CPB II and CPB III inhibited only the protein kinase C activity for histone phosphorylation. In the case of histone phosphorylation, all CPBs inhibited the protein kinase C activity in a concentration-dependent manner, and the IC50 (concentration required for 50% inhibition) value of CPB I was 70 nM. The inhibition of protein kinase C by CPB I was Ca(2+)-dependent, and did not disappear upon increasing the concentration of phosphatidyl-serine. Kinetic analysis by double-reciprocal plots indicated that CPB I interacted not only with phosphatidylserine but also with protein kinase C. Although CPB I partially interacts with phospholipid, it is conceivable that the inhibitory action of CPB I on protein kinase C results from direct interaction of CPB I with protein kinase C. Since CPBs are mainly present under the plasma membrane, it is presumed that CPB I is an endogenous inhibitor of protein kinase C, and according to intracellular circumstances, CPB II and CPB III may also be endogenous inhibitors.

Animals↗