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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 685 records · Page 38Linked to original sources

Nicardipine inhibits the endothelin-1-induced constriction of systemic capacitance and resistance vessels.

We estimated the effects of intravenous injection of endothelin-1 (ET-1; 400 pmol/kg) on the systemic capacitance and resistance vessels in anesthetized mongrel dogs by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR), respectively. In addition, the present study investigated the inhibiting action of nicardipine (NIC; 10 micrograms/kg bolus injection followed by 1.0-2.0 micrograms/kg/min continuous infusion) against the vasoconstrictor action of ET-1. We examined the effects of ET-1 (30 to 1,000 pmol/0.1 ml) on the femoral arterial system by measuring the percent changes in the perfusion pressure (% delta PP) of the femoral artery perfused with a constant flow, and investigated the effect of NIC on the vasoconstrictor action of ET-1 in this preparation. We obtained the following results: (a) Intravenous injection of ET-1 raised both TPR and MCP. However, in the presence of NIC, ET-1 raised TPR without influencing MCP. (b) Intra-arterial injection of ET-1 caused a dose-dependent increase in % delta PP. NIC shifted the dose-response curve of ET-1 for % delta PP to the right in a parallel fashion.

Animals↗

Effects of recombinant interleukin 4 on the growth and differentiation of blast progenitors stimulated with G-CSF, GM-CSF and IL-3 from acute myeloblastic leukaemia patients.

The effects of human recombinant interleukin 4 (rIL-4) on the growth of leukaemic blast progenitors were investigated. Cells obtained from 20 acute myeloblastic leukaemia (AML) patients were evaluated using the blast colony assay in methylcellulose and suspension cultures. While rIL-4 by itself did not show any colony stimulatory activity in the blast colony assay, it suppressed the blast colony formation in methylcellulose stimulated with G-CSF, GM-CSF or IL-3 in 14 patients. In another six patients, rIL-4 enhanced blast colony growth in four patients or did not show any significant effect with any CSF in two patients. In suspension cultures of 12 cases studied, the effects of rIL-4 on the clonogenic cell recoveries were essentially similar to the results of the blast colony assay in each case. In three patients, rIL-4 augmented the differentiation of the leukaemic cells to monocyte lineage. Further, the clinical outcome was significantly different between the patients whose blast progenitors were stimulated by rIL-4 and the patients whose blast progenitors were suppressed by rIL-4 (P less than 0.05); three out of four patients in the former group failed in achieving complete remission (CR), while 12 out of 14 patients in the latter group achieved CR. The results show that the effects of IL-4 on leukaemic blast progenitors were diverse and the responsiveness to IL-4 may be correlated with the prognoses of the patients.

Acute Disease↗

HSP47: a tissue-specific, transformation-sensitive, collagen-binding heat shock protein of chicken embryo fibroblasts.

We report the isolation and characterization of a cDNA clone encoding HSP47, a transformation-sensitive heat shock protein that binds to collagen. A cDNA library was prepared from total RNA isolated from heat-shocked chicken embryo fibroblasts and screened by using oligonucleotide mixtures prepared on the basis of the N-terminal amino acid sequence of biochemically purified HSP47. The cDNA insert contained 3,278 bp, which encoded a 15-amino-acid signal peptide and a mature protein coding region consisting of 390 amino acid residues; it also included part of the 5' noncoding region and a long 3' noncoding region. The deduced amino acid sequence revealed an RDEL sequence at the C terminus, which is a variant of the KDEL retention signal for retention of proteins in the endoplasmic reticulum. Northern (RNA) blot analyses and nuclear run-on assays established that the induction of HSP47 by heat shock and its suppression after transformation of chicken embryo fibroblasts by Rous sarcoma virus are regulated at the transcriptional level. A homology search revealed that this protein belongs to the serpin family, the superfamily of plasma serine protease inhibitors. Although structurally homologous to the serpins, HSP47 lacks the active site thought to be essential for the inhibition of proteases and does not appear to bind to intracellular proteases. HSP47 is the first heat shock protein found to be a member of the serpin superfamily. Conversely, it is the first serpin family member that is not secreted from cells, which could be explained by acquisition of the RDEL retention signal during evolution.

Amino Acid Sequence↗

Role of the kinin-kallikrein system in the vasodilator action of an angiotensin converting enzyme inhibitor (captopril) on the systemic resistance and capacitance vessels of dogs.

We investigated the vasodilator effects of captopril (CAP) on the systemic capacitance and resistance vessels by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR) that occurred in response to the intravenous injection of CAP (1 mg/kg) in open-chest dogs. The following five groups of dogs received CAP: (1) Group of untreated dogs, (2) TSA Group in which the dogs were subjected to total spinal anesthesia (TSA), (3) Ang II Group in which the dogs received a continuous intravenous infusion of angiotensin II (Ang II), (4) APR + Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with aprotinin (APR, 25,000 K.I.E.), a kallikrein inhibitor, and (5) IND + APR + Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with indomethacin (IND, 5 mg/kg), a prostaglandin synthesis inhibitor, and APR. 1) CAP significantly decreased TPR and MCP in the untreated Group. 2) CAP significantly decreased TPR and MCP in the TSA Group. There were no significant differences in percentage change of TPR (% delta TPR) and percentage change of MCP (% delta MCP) between the untreated and TSA Groups. 3) In the Ang II Group, CAP decreased the elevated TPR significantly, but hardly affected the elevated MCP. 4) CAP significantly decreased TPR without significant change in MCP in the APR + Ang II Group. The % delta TPR was significantly smaller in this Group than in the Ang II Group. 5) CAP significantly decreased TPR without significant change in MCP in the IND + APR + Ang II Group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Regulations of male-dominant P-450Md mRNA in rat liver by hormonal factors and xenobiotics.

Male-dominant P-450Md mRNA was undetectable in the livers of newborn rats. In female rat livers, the mRNA appeared at 17 days of age and then decreased to very low levels in the adult periods. The level of P-450Md mRNA in female rats was increased by phenobarbital or dexamethasone treatment, whereas the level in the males was depressed by methylcholanthrene. Hypophysectomy decreased the level of P-450Md mRNA in male rat livers, and continuous infusion or twice-daily injections of growth hormone to hypophysectomized rats caused further suppression or clear restoration, respectively, of the mRNA level.

Animals↗

Delayed traumatic intracerebellar hematoma: correlation between the location of the hematoma and the pre-existing cerebellar contusion--case report.

A rare case of delayed traumatic intracerebellar hematoma (DTIC1H) in a 54-year-old male achieved an excellent outcome without surgery. Analysis of this case and other reported cases suggests that DTIC1H occurs in two types: Group I with hematoma developing in previously contused areas, and Group II with hematoma developing in areas appearing normal on the initial computed tomographic scan. Group I hematomas occurred in the cerebellar cortex, but Group II hematomas occurred in the subcortical region or vermis where direct impact is less likely to have an effect. This suggests different mechanisms of development for DTIC1H.

Brain Concussion↗

[Biphenotypic acute leukemia with Ph1 chromosome, M-BCR-, myeloperoxidase+, and CALLA+].

A 63 year-old woman was referred to our hospital because of fever and increased number of blasts in the bone marrow. On physical examination she had slight hepatomegaly but no splenomegaly. Laboratory tests disclosed a hemoglobin level of 8.5 g/dl; a WBC count of 13,200/microliter with 26% blasts; a platelet count of 51,000/microliter. A bone marrow aspirate was normocellular with 74% blasts and 37% blasts were stained positive for myeloperoxidase. Cell surface markers for HLA-DR, CD10, CD19, CD13, CD33 were positive. Karyotype analysis revealed 46, XX, t (9q+; 22q-) and 45XX, -7, t (9q+; 22q-). Southern analysis showed rearrangement of immunoglobulin heavy chain but not T cell receptor beta gene. Rearrangements in M-BCR were not detected with 5' or 3' bcr probes. After 2 courses of chemotherapy, blasts decreased to 7% with recovery of normal elements and 11 out of 20 metaphases of the bone marrow cells were normal karyotype. These findings suggest that this case was de novo Ph1 positive acute leukemia which demonstrated both lymphoid and myeloid features.

Acute Disease↗

[Changes in the cytoskeletons during the differentiation of a myeloid leukemia cell line].

Cytoskeletons are supposed to play important roles in the cell growth, metastasis and invasion as well as the reduction of the adhesion to the matrix, which are characteristic of cancer cells. The dynamic changes of cytoskeletons were observed during the differentiation of mouse myelomonocytic leukemic cells, M1. We discuss an increase of the vimentin expression, which is correlated with the changes in the cell morphology, and a reduction of the vimentin degradation activity during the differentiation of M1 cells. And we also discuss about an increase of alpha-actinin synthesis, which is presumed to correlate with the cell adhesion and mobility.

Actinin↗

[A case of adult T cell leukemia/lymphoma with motor and sensory polyneuropathy].

A 62-year-old man was admitted to our hospital because of two months continuing paresthesia and muscle weakness of distal portions of the four limbs. On general physical examination, skin lesions, lymphadenopathy and hepatosplenomegaly were not found. Neurological examination revealed moderate weakness in the bilateral distal muscles of the lower limbs and left distal muscles of the upper limbs, and slight weakness in the right distal muscles of the upper limbs and the bilateral proximal muscles of the four limbs. Hand grasping powers were 24 kg and 2 kg on the right and left, respectively. The biceps, triceps and radial reflexes were decreased on the right, but normal on the left. The Achilles tendon reflex was decreased on the right and absent on the left. Paresthesia and superficial sensory disturbance were observed with glove and stocking distribution, which was more severe on the left side. The vibration and position senses were slightly decreased in the distal part of the lower limbs. On the laboratory examinations, serum anti-HTLV-I antibody was positive and no abnormal lymphocytes were observed in peripheral blood. Cerebrospinal fluid findings were normal, and anti-HTLV-I antibody was negative. Motor and sensory conduction velocities were normal or slightly decreased in all of the limb nerves examined, but the amplitudes of the compound muscle action potentials and the sensory nerve action potentials were asymmetrically decreased. Needle EMG showed fibrillation potentials and giant spikes with a reduction in number of motor unit potentials. The histological examination of the biopsied sural nerve revealed severe axonal degeneration without evidence of vasculitis or infiltration of abnormal lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-CD8 Ratio↗

[Non-Hodgkin's lymphoma with marked infiltration in calf muscle].

A 64-year-old male developed pain and marked swelling of his left calf muscle in September, 1989. Deep-vein thrombophlebitis was suspected, and therapy with warfarin sodium followed by urokinase was instituted. Because of unsatisfactory effect of the therapy, the patient was referred to another hospital on January 3rd 1990. A CT scan of the left leg showed a soft-tissue mass adjacent to the fibula. A biopsy of the mass revealed non-Hodgkin's lymphoma of diffuse medium-sized cell type. Immunohistologic examination confirmed B cell type. He was admitted to our hospital on January 31st 1990. A chest roentgenogram showed right pleural effusion. A CT scan of the abdomen revealed a space-occupying lesion in the liver. A Gallium scintigraphy showed markedly increased isotope uptake in the left calf and liver. He was classed as a Stage IV B. He responded well to combination chemotherapy with cyclophosphamide, THP-adriamycin, VP-16, and prednisolone and achieved a complete remission. Although prominent infiltration of lymphoma cells in skeletal muscles is rarely reported, it is important to perform the biopsy promptly when the mass is found in a muscle. In this case report, we describe a rare case of non-Hodgkin's lymphoma with muscle invasion presented as marked calf muscle swelling.

Humans↗

[Modified CHOP therapy in patients with non-Hodgkin's lymphoma].

From July 1983 to December 1989, 31 previously untreated patients with non-Hodgkin's lymphoma were treated with modified CHOP regimen (cyclophosphamide 300 mg/m2 on day 1, aclacinomycin 40 mg/m2 on day 1, vincristine 0.7 mg/m2 on day 1 and prednisolone 40 mg/m2 on days 1-5). The therapy was repeated at 2-week intervals. The complete response rate was 66.7% for clinical stage (CS) II according to the Ann Arbor criteria, 60.0% for CS III and 33.3% for CS IV, respectively. The 5-year survival rate was 100% for CS II, 36.6% for CS III and 34.6% for CS IV, respectively. Clinical effects of modified CHOP regimen were almost the same as those of other therapies including adriamycin from the standpoint of 5-year survival rate. On the other hand, the myelosuppression accompanying modified CHOP therapy was not severe. Only one patient had a white blood count below 1,000/microliters during 6 courses of the therapy. It is thought that this regimen is useful to enhance the quality of life of patients because of no severe complications such as myelosuppression.

Aclarubicin↗

[Multi-center evaluation of Showa disk susceptibility to presumptively determine minimum inhibitory concentrations through linear regression analysis].

To confirm the reliability of minimum inhibitory concentrations (MICs) determined by use of predefined linear regressions to bacterial growth inhibitory zone diameter on Showa disk susceptibility test, the multi-center evaluation along daily routines was performed in comparison with the standard agar dilution method. In total, 4,107 (89.0%) of 4,613 testings gave comparable MICs with 4-fold or less differences to those determined by the standard agar dilutions. The agreement of MICs (less than or equal to 4-fold differences) for gram-negative rods, excluding Pseudomonas aeruginosa, against 10 antimicrobial agents was estimated to 92.1%, and those for gram-positive cocci against 9 agents and for the strains of Pseudomonas aeruginosa against 8 agents were 84.5% and 81.7%, respectively. With these results, we can conclude that, under the well-controlled test procedures, the MIC correlates determined by Showa disk susceptibility test are enough comparable to those determined by the standard agar dilution method.

Anti-Bacterial Agents↗

Interleukin 1 autocrine growth system in human multiple myeloma.

The role of interleukin 1 (IL 1) in the growth of human multiple myeloma cells was studied in vitro. In the culture supernatant of myeloma cells, IL 1-like activities were detected by the stimulating on murine thymocyte proliferative response and these activities were completely inhibited by anti-IL 1 beta antibody but not by anti-IL 1 alpha antibody. Recombinant human IL 1 alpha (alpha) and IL 1 beta (beta) enhanced the proliferation of myeloma cells freshly isolated from the bone marrow of patients with multiple myeloma. Moreover, the spontaneous growth of myeloma cells was partly inhibited by anti-IL 1 beta antibody but not by anti-IL 1 alpha antibody. IL 1 receptor was detected on the surface of 50% of the myeloma cells by flow cytofluorometric analysis. The expression of IL 1 receptor (IL 1R) on myeloma cells was also analyzed using a binding assay with 125I-labeled IL 1 alpha. By Scatchard plot analysis, two classes of IL 1R were found on the myeloma cells. The major class (2700-7200 sites/cell) had the lower affinity (Kd = 0.88-1.2 x 10(-9) M) and the minor class (70-500 sites/cell) had the higher affinity (Kd = 3.1 - 38.0 x 10(-12) M). Furthermore, a tendency for a proliferation of IL 1R-positive myeloma cells to be induced by adding exogenous IL 1 was observed. These results suggest IL 1 beta to be one of the autocrine growth factors for multiple myeloma cells.

Antibodies↗

[Detection of methicillin-resistant Staphylococcus aureus by the Showa disk].

The Showa disk susceptibility test using two penicillinase-resistant penicillins (PRPs: methicillin and oxacillin) and four cephalosporins (cefazolin, cefmetazole, ceftizoxime, and latamoxef) was evaluated to discriminate between the strains of Staphylococcus aureus resistant to methicillin (MRSA) and those susceptible (MSSA). Among 129 MRSA and 112 MSSA strains, significant numbers of MRSA found to be false-susceptible to PRPs, especially when incubated at 37 degrees C. Using agar plates supplemented with 5% NaCl, oxacillin disk correctly categorized all the MRSA and MSSA strains, but two MSSA strains were mischaracterized with methicillin disk. All the MSSA strains found to be susceptible against cephalosporins tested, but significant numbers of MRSA were also interpreted to be susceptible. Only the result of ceftizoxime disk susceptibility test highly correlated with methicillin resistance, when incubated at 35 degrees C. All the MRSA did not produce any significant bacterial growth inhibitory zone around the disk, whereas all the MSSA found to be susceptible (19 mm or more), e.g., 100% correlation. With these data, we recommend that ceftizoxime disk susceptibility test, incubated at 35 degrees C, provides a more reliable method to characterize the strains of MRSA and MSSA. The interpretive breakpoint would be used as; less than or equal to 16 mm (greater than or equal to 25 micrograms/ml) for MRSA.

Methicillin Resistance↗

Promoter selectivity of Escherichia coli RNA polymerase: effect of base substitutions in the promoter -35 region on promoter strength.

A set of 18 variant lac UV5 promoters was constructed, each carrying a single base substitution within the -35 region (nucleotide positions from -36 to -31 relative to the transcription start site). Using truncated DNA fragments carrying these variant promoters and purified Escherichia coli RNA polymerase holoenzyme, in vitro mixed transcription assays were performed to determine two parameters governing promoter strength: i.e., the binding affinity to RNA polymerase (parameter I) and the rate of open complex formation (parameter II). The following conclusions were drawn from the data presented: (1) Alteration in the promoter strength of variant promoters is dependent on both the position and base species of substitutions; (2) the consensus sequence (TTGACA) exhibits the highest values for both parameters; (3) base substitutions at nucleotide position -34 cause marked effect on both parameters; (4) cytosine at nucleotide position -32 can not be replaced with other nucleotides without significant reduction of the promoter strength; and (5) base substitution at nucleotide position -31 exerts only a little effect on parameter I. All these findings were confirmed by abortive initiation assays.

Base Sequence↗

Effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine on blast progenitors of acute myeloblastic leukemia.

To determine the antileukemic effect of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a synthetic masked compound of 1-beta-D-arabinofuranosylcytosine, the pharmacokinetics and suppressive effect on leukemic blast progenitors of BH-AC were studied. When BH-AC was added to the suspension culture of leukemic cells, BH-AC gradually decreased in concentration in the culture media and was rapidly taken into the cellular fraction. The conversion from BH-AC to 1-beta-D-arabinofuranosylcytosine was noted in both the culture media and the cellular fraction. The concentration of 1-beta-D-arabinofuranosylcytosine converted from BH-AC in the culture medium gradually increased during 7 days of culture, although the rate of conversion was variable among the samples. BH-AC suppressed primary and secondary blast colony formation in a dose responsive manner. BH-AC also suppressed the recovery of clonogenic cells in suspension culture. The suppression by BH-AC was more prominent in secondary blast colony formation and the recovery of clonogenic cells in suspension culture than in primary blast colony formation. Secondary blast colony formation and the recovery of clonogenic cells in suspension are considered to reflect the self-renewal of blast progenitors, while primary blast colony formation is considered to reflect the terminal divisions of blast progenitors. The results obtained in the present study suggest that BH-AC is more effective to suppress the self-renewal of blast progenitors than the terminal divisions. The findings offer a theoretical basis in the utility of BH-AC in the therapy of acute myeloblastic leukemia.

Adult↗