Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 397 records · Page 22Linked to original sources

PubMed1994

Generation of hydrogen peroxide by varicella-zoster virus-stimulated polymorphonuclear leukocytes.

BACKGROUND: In varicella-zoster virus (VZV) infections, the initial response in cutaneous lesions is predominantly polymorphonuclear leukocytes (PMN). However, interaction of VZV and PMN has not yet been fully defined. OBJECTIVES: To explore the potential role of PMN in VZV infections, we investigated the ability of PMN to generate hydrogen peroxide (H(2)O(2)) after stimulation with VZV antigen. STUDY DESIGN: H(2)O(2), one of the reactive oxygen species, was measured by cytofluorography after PMN were incubated with varicella-zoster virus (VZV) antigen in the presence of seropositive or seronegative serum. RESULTS: H(2)O(2) was detectable in unseparated PMN obtained from seropositive children and adults, while unseparated PMN of seronegative donors were not capable of generating H(2)O(2). Separated PMN obtained from either seropositive or seronegative donors were capable of generating H(2)O(2) in the presence of seropositive serum. However, H(2)O(2) was not detectable in separated PMN of seropositive donors in the presence of seronegative serum. The of H(2)O(2) generation did not correlate with concentrations of serum antibodies to VZV. CONCLUSIONS: VZV antigen-antibody complexes might induce H(2)O(2) generation by PMN.

Journal Article↗

PubMed1994

Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA.

A series of Human Immunodeficiency Virus type-1 protease (HIV-1 PR) inhibitors that contain 3-amino-2-hydroxy-4-phenylbutanoic acid (AHPBA) at the scission site of the substrate were prepared and evaluated for their inhibitory activity. Preliminary studies on the chain length of inhibitors and the hydroxyl configuration of AHPBA indicated that small (2S,3S)-derivatives, composed of the regions between the P3 and P2' sites, showed enough inhibitory activity toward HIV-1 PR to become prototypes for further structural modification. Systematic replacement at the sites from P3 to P2' revealed that some bicyclic heteroarylcarbonyl derivatives possessed strong potency and good enzyme selectivity.

Amino Acid Sequence↗

PubMed1994

Chemical modification and site-directed mutagenesis of Tyr36 of 3-isopropylmalate dehydrogenase from Thermus thermophilus HB8.

3-Isopropylmalate dehydrogenase from an extreme thermophile, Thermus thermophilus HB8, was chemically modified with tetranitromethane which nitrated 1.5-2.0 Tyr residues per subunit. The nitration was biphasic and parallel to the loss of activity. The modified residue in the first phase was identified to be Tyr36, which is distantly located from the active site of the enzyme. The function of Tyr36 was investigated by site-specific replacement with Phe. The Michaelis constant for the substrate or co-enzyme was not altered by the replacement, whereas the catalytic constant decreased down to approximately 5%. X-ray analysis of the mutant enzyme revealed that Arg94 moved the largest distance among the active site residues, that is, the NH1 and NH2 of the guanidino group moved 1.11 and 1.32 A respectively. The results suggest that Arg94 is responsible for the enzyme catalysis.

3-Isopropylmalate Dehydrogenase↗

PubMed1994

Three-dimensional structures of chimeric enzymes between Bacillus subtilis and Thermus thermophilus 3-isopropylmalate dehydrogenases.

The 3-D structures of two chimeric enzymes (4M6T and 2T2M6T) between the Bacillus subtilis and Thermus thermophilus 3-isopropylmalate dehydrogenases were analysed by X-ray diffraction in order to investigate their different thermostabilities. The structure of 2T2M6T was determined by the difference Fourier method and that of 4M6T by rigid body refinement, as based on the structure of the T. thermophilus enzyme. These structures were refined stereochemically to an R-factor of 0.193 at 2.5 A resolution for 4M6T and to an R-factor of 0.195 at 2.2 A resolution for 2T2M6T. The 3-D structures of 4M6T and 2T2M6T were very close to the structure of the T. thermophilus enzyme, conspicuous differences being at the molecular surface. In particular, 2T2M6T having a larger reduction in thermostability was more closely related to the T. thermophilus enzyme. However, their correlations between C alpha-atom displacements and the root squares of the temperature factors were significantly different from each other.

3-Isopropylmalate Dehydrogenase↗

PubMed1994

Cytotoxicity against varicella zoster virus infected targets in children with acute leukemia.

To eliminate the role of natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), and polymorphonuclear leukocyte (PMN)-mediated cytotoxicity in Varicella zoster virus (VZV) infections, peripheral blood mononuclear cell (PBMC)-mediated NK and ADCC, and phorbol myristate acetate-stimulated PMN-mediated cytotoxicity against VZV-infected targets were studied in children with leukemia. Natural killer and PMN-mediated cytotoxic activity was depressed for 6 months after complete remission and ADCC activity was depressed for 1 year after complete remission. The magnitude of three cytotoxic mechanisms in leukemic children gradually increased while they continued in complete remission. These results suggested that decreased cytotoxic activities of PBMC and PMN might contribute to serious VZV infections and susceptibility to herpes zoster in leukemic children.

Adolescent↗

PubMed1994

A flow cytometric method for measurement of hydrogen peroxide generation by pediatric polymorphonuclear leukocytes stimulated by Staphylococcus aureus and Escherichia coli.

The generation of hydrogen peroxide (H2O2), one of the reactive oxygen species, by polymorphonuclear leukocytes (PMN) stimulated by Staphylococcus aureus and Escherichia coli was studied in infants by cytofluorography. After heparinized whole blood was incubated with bacteria for 60 min, generated H2O2 was measured. The positive rate of H2O2 generation of PMN and mean fluorescent intensity of positive PMN stimulated by S. aureus and E. coli were significantly reduced in infants aged < 1 year and H2O2 generation increased with advancing age. In 10-15 year old children, the level of generated H2O2 reached adult levels. When sera from 1 year old children were added to separated PMN from healthy adults, H2O2 generation was reduced. In contrast, H2O2 generation by PMN from 1 year old children was increased by the addition of adult sera. These results suggest that the ability to generate H2O2 in response to S. aureus and E. coli is lower in infants and that such reduced activity may be related to the susceptibility of such infants to S. aureus and E. coli infections.

Adolescent↗

PubMed1994

Effect of varicella zoster virus antigen-antibody complexes on hydrogen peroxide generation by human polymorphonuclear leukocytes.

Hydrogen peroxide (H2O2) generation by human polymorphonuclear leukocytes (PMN) incubated with varicella zoster virus (VZV) antigen was studied by cytofluorography. Hydrogen peroxide generation was detected in the presence of VZV-seropositive sera. When seropositive sera were heat-inactivated, H2O2 generation was reduced. When PMN were pre-incubated with Leu-11b, a monoclonal antibody to the Fc receptor on PMN, H2O2 generation was also reduced. These results suggest that VZV antigen-antibody-complement complexes induce H2O2 generation by PMN after these complexes attach to Fc receptors on PMN.

Antibodies, Viral↗

PubMed1994

Consecutive cerebral MRI findings of acute relapsing disseminated encephalomyelitis.

A seven year old girl with acute relapsing disseminated encephalomyelitis (ARDEM) was observed with serial magnetic resonance imaging (MRI) examination. She had the first encephalomyelitis episode at the age of 2 years 9 months. She entered remission with steroid therapy. She suffered a recurrence at the age of 7. Steroid therapy was instituted and consecutive magnetic resonance imaging (MRI) was performed. In spite of rapid improvement of neurological abnormality with steroid and steroid pulse therapy, disseminated high intensity lesions in T2-weighted imaging which were considered as demyelination remained for a long time. Magnetic resonance imaging seems to be most suitable for evaluating the clinical condition and long-term follow-up of ARDEM.

Adrenal Cortex Hormones↗

PubMed1994

Interferon-gamma induces interleukin-3 release from peripheral blood eosinophils.

Interferon-gamma (IFN-gamma) upregulates eosinophil effector functions and prolongs the in vitro survival of eosinophils. We examined the possible capacity of IFN-gamma to stimulate eosinophils to produce eosinophil-activating cytokines. Eosinophils purified from mild atopic volunteers were cultured with 100 U/ml IFN-gamma. Viability of eosinophils was counted and supernatants were tested for the presence of cytokines by neutralization of eosinophil viability-enhancing activity with specific antibodies to IFN-gamma, interleukin-5 (IL-5), IL-3, or granulocyte-macrophage colony-stimulating factor (GM-CSF). IFN-gamma-enhanced eosinophil viability was up to 95% on the 4th day of culture. Pretreatment with anti-IL-3 antibody partially blocked the IFN-gamma-enhanced eosinophil survival. IFN-gamma-stimulated eosinophil supernatants had eosinophil survival. IFN-gamma-stimulated eosinophil supernatants had eosinophil viability-enhancing activity that was blocked by pretreatment not only with anti-IFN-gamma but also with anti-IL-3. Antibodies to IL-5 or GM-CSF did not have the blocking effect. To further confirm the production of IL-3 by eosinophils, we performed reverse transcription polymerase chain reaction (RT-PCR) for IL-3 messenger RNA (mRNA) in IFN-gamma-stimulated eosinophils. Significant IL-3 mRNA expression in eosinophils was observed at 6 h of incubation with IFN-gamma. These results suggest that IFN-gamma stimulates the autocrine function of eosinophils and may play an important role in allergic inflammation.

Cell Survival↗

PubMed1994

Light microscopical immunohistochemical study on parathyroid adenoma in primary hyperparathyroidism.

Fifteen adenomatous parathyroid glands obtained from 15 patients with primary hyperparathyroidism were examined both pathologically and immunohistochemically and connected with the clinical data for each patient. Four consecutive sections of the largest section surface of each resected adenomatous parathyroid gland were utilized for 4 kinds of stains, that is, hematoxylin-eosin, Grimelius and the immunohistochemical stains for parathyroid hormone (PTH) and chromogranin A. The results were as follows: (1) The large adenomatous parathyroid glands showed strong reactions to PTH as well as chromogranin A and Grimelius. On the other hand, the parathyroid adenoma obtained from a 9-year-old boy with hypercalcemic crisis showed almost no stain-positive cells for both PTH and chromogranin A. It is assumed that the former phenomenon reflects a substantial storage of secretory granules, while the latter reflects exhaustion of these granules. (2) The normal parathyroid cells in the neoplastic parathyroid glands generally showed stronger reactions to PTH and chromogranin A than neoplastic parathyroid cells. This suggests that normal cells in the neoplastic parathyroid glands may have their release of PTH rather than its synthesis suppressed, and also might support the hypothesis of some authors that chromogranin A or SP-I might contribute to stabilization of PTH or the secretory vesicle.

Adenoma↗

PubMed1994

Ossification of the Achilles tendon: a case report.

Ossification of the Achilles tendon is a rare condition. We recently treated a patient with ossification of bilateral Achilles tendons. The patient was a 50 year old male whose chief complaint was discomfort around the Achilles tendon. He had a previous history of treatment of bilateral club feet. On the roentgenograms, the length of the bony mass in the Achilles tendon was 5.5 cm on the right side and 1.5 cm on the left side. The left side was treated by surgical removal of a bony mass and suture of the tendon. Microscopic examination of the extirpated specimen revealed bone formation through enchondral and intramembranous ossification in the Achilles tendon.

Achilles Tendon↗

PubMed1994

Studies of human immunodeficiency virus type 1 (HIV-1) protease inhibitors. III. Structure-activity relationship of HIV-1 protease inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere.

Systematic replacement of the P4-P2 subsites of substrate-based human immunodeficiency virus type 1 protease (HIV-1 PR) inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere (Cha-psi [H.E.]-Ala) at positions corresponding to the scissile sites of substrates was carried out. The structure-activity relationship revealed that compounds with the combination of hydrophilic P3 and beta-branched hydrophobic P2 amino acids generally showed strong inhibitory activity against HIV-1 PR. In particular, compounds 4 (Boc-Orn-Val-Cha-psi [H.E.]-Ala-NHBun; Bu(n) = n-butyl, Ki = 11 nM) and 6 (Z-Orn-Val-Cha-psi [H.E.]-Ala-NHBun, Ki = 8 nM) exhibited good enzyme selectivity, possessing no significant inhibitory activities toward closely related aspartic proteases, pepsin, cathepsin D, and renin. As a possible model system for (anti-Mo-MSV/MLV complex (Mo-MSV = Moloney murine sarcoma virus; MLV = murine leukemia virus)) activity was investigated. Both compounds were found to inhibit moderately the focus formation of Mo-MSV/MLV complex in NIH3T3 cells (compound 4, IC50 = 1.8 microM; compound 6, IC50 = 1.0 microM).

Amino Acid Sequence↗

PubMed1994

Cytokines and cytokine receptors in acute lymphoblastic leukemia expressing myeloid markers--role in growth regulation.

There is no evidence that cancer cells including leukemic cells are immortal. It has been clearly indicated that certain cytokines can significantly stimulate leukemic cell proliferation in vitro, and sustain the circuit of autocrine or paracrine stimulation. The biological roles of cytokines and cytokine receptors have been intensively investigated in acute leukemia. Recently coexpression of both lymphoid and myeloid features on a single leukemic cell has been well recognized using a flowcytometric technique. Studies of ALL cells expressing myeloid markers (My+ ALL) have indicated that the profiles of cytokines and cytokine receptors expressed by My+ ALL show both similarities and differences to those in My- ALL or acute myelogenous leukemia (AML), suggesting that My+ ALL cells may originate from uncommitted hematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages. The exact assessment of cytokine response of leukemic cells would provide an important tool for phenotyping acute leukemia based on the growth properties of the cells (cytokine phenotyping), in addition to the morphologic classification and immunological surface phenotyping. Additionally alteration of sensitivity to cytotoxic anticancer drugs by cytokine stimulation may be the new strategy for biologic therapy of acute leukemia.

Antigens, Surface↗

PubMed1994

Shedding of CD9 antigen in acute lymphoblastic leukemia.

A leukemia-associated CD9 glycoprotein antigen released into the extracellular milieu from acute lymphoblastic leukemia cells has been detected using a unique lectin-monoclonal antibody immunoassay. It has been demonstrated that the release of CD9 antigen is an active process and is associated with active cell growth. In addition, the difference of carbohydrate moiety, and hence glycosylation, in the CD9 antigen derived from lymphoblasts and neuroblasts was verified using lectin affinity chromatography. The lectin affinity of the carbohydrate moiety of lymphoblast CD9 antigen would indicate the presence of N-linked oligosaccharide chains having groups of N-acetyl glucosamine residues, a mannose core and a terminal D-galactose. The soluble CD9 antigen is specifically detected in plasma from ALL patients at the time of diagnosis, in cerebrospinal fluid from patients with central nervous system involvement, and spent medium from CD9-positive leukemic blasts obtained at the time of diagnosis. Interestingly when bone marrow cells taken from patients in complete remission were studied, a distinct amount of CD9 antigen was released into spent medium in some of the cases. All of these patients have subsequently developed hematological relapse. The present data suggest that shedding of CD9 antigen by leukemic cells may enable the clinical monitoring of residual leukemic cell burden.

Antigens, CD↗

PubMed1994

[A case of angiosarcoma with von Recklinghausen's disease].

We treated a patient with von Recklinghausen's disease and angiosarcoma. This combination has not been reported in Japan to the best of our knowledge. An emergency operation for massive gastrointestinal bleeding was performed on a 68-year-old woman with von Recklinghausen's disease, who had been known to have a retroperitoneal tumor; The bleeding was controlled and the tumor was also resected. Postoperative course was uneventful also but one month after operation intra-abdominal and intrathoracic bleeding developed, and the patient died of respiratory failure. Autopsy showed hemorrhagic lesions, which were diagnosed pathologically metastatic angiosarcoma. The possibility of hemorrhagic lesions in the patients with von Recklinghausen's disease should be kept in mind.

Aged↗

PubMed1994

[Pharmacokinetic and clinical studies of cefozopran in the field of pediatrics].

Cefozopran (CZOP) was administered intravenously to 22 infants (aged 3 months to 15 years) with infections excluding suppurative meningitis in doses of 10 to 40 mg/kg 3 to 4 times daily for periods of 3 to 16 days and its efficacy and safety in infantile infections as well as pharmacokinetic parameters were determined. The half-lives of CZOP after intravenous administration at doses of 10, 20 and 40 mg/kg were 2.84, 2.36 +/- 0.67, and 2.48 hours, respectively. The rates of recovery in the urine within 6 hours of administration were 83.6%, 62.9 +/- 23.1%, and 77.3%, respectively. The subjects for whom drug responses were evaluable consisted of 1 case of suppurative meningitis, 8 cases of respiratory tract infection, 2 cases of urinary tract infection, 2 cases of oral infection, 2 cases of pharyngotonsillitis, 1 case of skin soft tissue infection, and 1 case of external otitis, totaling 17 cases. The efficacy rate was 88.2%. The drug proved so effective on suppurative meningitis in particular that the patient was healed without leaving any sequela behind. Seven strains were identified as causative pathogens (5 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus, 1 strain of group B Streptococcus) isolated from 6 patients. All but 1 strain were eradicated (the rate of eradication 83.3%). In the patients with suppurative meningitis the bacterial count of spinal fluid was markedly decreased 6 hours after drug administration and the organism was eradicated in 45 hours. Eruption was noted in 1 patient as a side effect of CZOP, but disappeared soon after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

[Influence of extracorporeal shock wave lithotripsy (ESWL) on renal function assessed by 99mTc-DMSA scintigraphy: comparative analysis between ESWL and percutaneous nephroureterolithotripsy (PNL)].

99mTc-DMSA renal scintigraphy was utilized to investigate the influence of ESWL on renal function in comparison with that of PNL. In the beginning, the reproducibility of renal uptake rate by the scintigraphy was examined in eleven healthy volunteers under both non-diuretic and diuretic states. The renal uptake rate was shown to be sufficiently reproducible in the same person in the two different trials. However, the differences and the standard deviations were shown to be a few percentages, which were not statistically significant. Changes in the repeated renal uptake rate seem to indicate not only changes of renal function with the treatment but also some technical errors. Herein, to investigate changes in renal function of the therapeutic side, the uptake ratio rate (rate of uptake rate in the therapeutic side/uptake rate in the contral lateral side) was utilized instead of uptake rate. Renal scintigraphy was carried out in 48 patients with unilateral renal stones before and after ESWL or PNL monotherapy or the combined ESWL and PNL therapies. Within one week of treatment, the uptake ratio rate significantly decreased in patients with PNL or the combined ESWL and PNL, although DMSA uptake rate in the therapeutic side did not significantly changes. Neither renal uptake rate nor uptake ratio rate significantly changed after ESWL treatment. There was no significant difference in changes of uptake ratio rate between Siemens Lithostars Plus and the improved Dornier HM-3 lithotriptors. This study indicated that ESWL monotherapy did not affect the uptake ratio rate, although PNL monotherapy and the combined ESWL and PNL therapies may affect the uptake ratio rate to some extent.

Adult↗

PubMed1994

[Laboratory and clinical studies on combined effects of fosfomycin plus sulbactam/cefoperazone for mixed infections of MRSA and Pseudomonas aeruginosa].

The time-lag/sequential/step by step chemotherapy by fosfomycin plus sulbactam/cefoperazone including a short time small dose of steroid was done for 27 severely infected patients suffered from various cancer or other severe basal diseases. And the staggered "intensive" chemotherapy with added arbekacin or vancomycin to the previous staggered chemotherapy was done against 13 severely infected patients having MRSAs among their infecting pathogens. 1. Bacteriological effects Pseudomonas aeruginosa 6/8, Staphylococcus epidermidis 5/5, Enterococcus faecalis 3/6, Acinetobacter calcoaceticus 2/2, Klebsiella pneumoniae 2/2, MRSA 2/2, Xanthomonas maltophilia 2/3 and other 10/10 were eradicated (84.2%) by the staggered chemotherapy and MRSA 7/13, P. aeruginosa 3/4, E. faecalis 3/5, A. calcoaceticus 2/2, X. maltophilia 1/1 and others 2/2 were eradicated (53.8% in MRSA, 78.6% in others and 66.7% in total) and 3 of MRSAs were colonized. 2. Clinical effects 1) Staggered chemotherapy: Excellent 18/27, good 8/27, fair 1/27, poor 0/27 (96.3%). 2) Staggered "intensive" chemotherapy: Excellent 6/13, good 4/13, fair 2/13, poor 1/13 (76.9%) in total: excellent 60.0%, efficacy rate 90.0%.

Adult↗