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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 235 records · Page 13Linked to original sources

Detection of tet(K) and tet(M) in Staphylococcus aureus of Asian countries by the polymerase chain reaction.

This study describes the use of the polymerase chain reaction (PCR) to detect the tet(K) and tet(M) tetracycline resistance genes in Staphylococcus aureus. Primers based on the DNA sequence of the tet(K) and tet(M) genes from S. aureus were used as primers in the PCR assay to detect the presence of genes for resistance to tetracycline and minocycline. Two-hundred and fifteen isolates of S. aureus from Asian countries as Japan, Indonesia, China, Korea and Thailand were examined, and the results confirm that tet(K) specifies resistance to tetracycline but not to minocycline and tet(M) specifies resistance to both tetracycline and minocycline. We observed two different types of clinical isolates of S. aureus strains resistant to minocycline and tetracycline: the first carried only the tet(M) gene, while the second carried both the tet(M) and the tet(K) genes. Almost all of the clinical isolates of S. aureus resistant to minocycline and tetracycline from Indonesia, China and Thailand carried both tet(M) and tet(K) genes, while most of clinical isolates of S. aureuss from Japan and Korea carried only tet(M) gene.

Anti-Bacterial Agents↗

[Ganciclovir prophylaxis for cytomegalovirus interstitial pneumonitis after allogeneic bone marrow transplantation].

We evaluated the efficacy of ganciclovir to prevent the development of cytomegalovirus interstitial pneumonitis (CMV-IP) in patients with bone marrow transplants. Of 35 patients enrolled in this study, 33 were seropositive for CMV or had seropositive donors, and two were seronegative before transplant but were positive for CMV examined by polymerase chain reaction (PCR) on days 30-37. Ganciclovir was given at a dose of 250 mg/body daily from day 30-37 to day 70. Blood, throat swabs, urine and bronchoalveolar-lavage fluid (BALF) were screened for CMV by PCR on days 30-37, 70 and 100. CVM-IP developed in two of 35 patients (5.7%) who received ganciclovir for prophylaxis, as compared with six of 39 historical controls who did not receive ganciclovir. A significant reduction of CMV detection by PCR in blood, throat swabs, and BALF was observed after administration of ganciclovir, on day 70. The incidence of neutropenia, thrombopenia and renal impairment in the study period showed no difference between the study group and the historical control. Early prophylactic use of ganciclovir appears to reduce the risk of CMV disease in allogeneic transplant recipients with positive serology or positive CMV-PCR.

Adolescent↗

[Chronic myelocytic leukemia associated with cytomegalovirus induced sialoadenitis after unrelated allogeneic bone marrow transplantation].

A 26-year-old male with chronic myelocytic leukemia was admitted for unrelated allogeneic bone marrow transplantation (BMT). After BMT, he developed swelling of biateral submandibular glands accompanied with pneumonitis possibly due to cytomegalovirus (CMV). Biopsy from the left submandibular gland showed giant cells with nuclear inclusion bodies that were positive for anti-CMV-IE monoclonal antibody, there fore cytomegalic sialoadenitis was diagnosed. The administration of ganciclovir resulted in resolution of the pnumonitis and submandibular gland swelling. Although cytomegalic sialoadenitis is not a life-threating complication in BMT patients, it should be noted that biopsy is very useful for the diagnosis of systemic cytomegalovirus infection.

Adult↗

[Hypoplastic mixed lineage leukemia successfully treated with low-dose cytosine arabinoside].

A 54-year-old male was admitted because of dyspnea on exercise. His peripheral blood revealed pancytopenia with severely hypoplastic bone marrow. Bone marrow aspiration showed a marked hypocellular marrow with 62.4% of blast cells. Cytochemical studies showed that peroxidase activity, alpha-nephtyl buthylate esterase activity and PAS reaction were negative, and that only ASD-chroloacetate esterase activity was positive. Surface marker analysis of blast cells showed positive result for CD5, 7, 33 and 34 antigens. The T-cell receptor beta gene was rearranged, but the immunoglobulin H chain gene showed a germ line configuration. Terminal Deoxynucleotydyl Transferase (TdT) was positive, but cellular surface and cytoplasmic immunoglobulin were not recognized. A diagnosis of hypoplastic mixed lineage leukemia was made and treated with low dose cytosine arabinoside, he resulted in complete remission. The relation between hypoplastic leukemia, AML-M0 and mixed lineage leukemia was also discussed.

Antimetabolites, Antineoplastic↗

[Pancytopenia and Pneumocystis carinii pneumonia associated with low dose methotrexate pulse therapy for rheumatoid arthritis--case report and review of literature].

Low-dose weekly pulse MTX therapy is effective for rheumatoid arthritis (RA) and is used for patients with RA who are unresponsive to conventional disease-modifying antirheumatic drugs (DMARDs). We used MTX to a 62-year-old man with RA who had received DMARDs for 5 years. MTX was effective for RA but after 12 weeks MTX therapy started, he complicated pancytopenia and developed Pneumocystis carinii pneumonia. We reviewed all RA patients reported in Japan and in the world from 1965, complicated with Pancytopenia (37 cases) and Pneumocystis carinii pneumonia (13 cases) after MTX therapy. Results were as following; (1) MTX should not be used with TMP-SMX. and risk factors for pancytopenia were (2) age over 60 years old (3) renal hypofunction (4) use of NSAID.

Age Factors↗

[Low-grade non-Hodgkin's lymphoma: intensive combined chemotherapy].

The efficacy of various combination chemotherapies employed for the 37 patients with low-grade non-Hodgkin's lymphoma between 1981 and 1994 was evaluated retrospectively. The overall survival at 5 years was 68%. The 5-year survival of the 27 patients achieving complete response (CR) was 87%, which was significantly higher than that of 9 patients with partial response (p = 0.0005). The CR rate of stage III and IV patients was 64% for the 22 patients treated with ACOMP-B (D), and was 38% for 8 others treated with milder chemotherapy regimens including VEPA. The 22 advanced stage patients had a 5-year survival of 88% after the treatment with ACOMP-B (D) and 69% of them remained free of disease at 5 years. In this group no relapse occurred beyond 1.6 years after treatment. These findings suggest a possible role of third generation chemotherapy in the treatment of patients with advanced-stage low-grade non-Hodgkin's lymphoma.

Adult↗

Acquired type 2A von Willebrand disease in chronic myelocytic leukemia.

Acquired von Willebrand disease (vWD) has been described in a few patients with chronic myelocytic leukemia (CML). We present here acquired type 2 vWD associated with CML and provide characterization of an inhibitor to von Willebrand factor (vWF) from this patient. His bleeding time was prolonged. Ristocetin-induced platelet agglutination was abolished whereas botrocetin-mediated aggregation was normal. Multimeric analysis of vWF from patient's plasma showed that larger sizes of multimers were reduced. His past and family histories were negative for bleeding tendency. These results suggested that acquired type 2 vWD was present during his clinical course. The inhibitor was purified by Staphylococcal protein A, suggesting an IgG antibody. Both binding of 125I-vWF to GPIb and platelet agglutination by ristocetin were inhibited by the patient IgG with the concentrations of competing substances necessary to inhibit specific binding by 50% (IC50s) of 260 micrograms/ml and 420 micrograms/ml, respectively. However, the IgG had no effect on these studies mediated by botrocetin. The IgG only reacted with intact vWF and a 39/34 kDa fragment of vWF. These results indicate that the recognition of GPIb binding site(s) on vWF by the IgG is a central pathogenesis of acquired type 2 vWD in this case.

Bleeding Time↗

Value of intraoperative intrathoracic ultrasonography during video-assisted thoracoscopic pulmonary resection.

Recent advances in endoscopic surgical equipment, video monitoring, and endoscopic surgical techniques have expanded the application of thoracoscopic surgery to pulmonary resection. One of the major limitations of this technique is the difficulty in identifying invisible pulmonary nodules in which manual palpation is not possible. To resolve this problem, we employed intraoperative intrathoracic ultrasonography during video-assisted thoracoscopic pulmonary resection. We conclude that intraoperative ultrasonography during thoracoscopic pulmonary resection is useful to identify pulmonary nodules, except inflammatory lesions.

Adult↗

An evaluation of various indices of body weight change and their relationship with coronary risk factors.

OBJECTIVE: To compare interrelationships between different indices and their relationship with cardiovascular disease risk factors. METHOD: Longitudinal comparison among weight change indices in the observation of a fixed population from age 21-40. SUBJECTS: 215 non-obese blue-collar workers in a steel company. MEASUREMENTS: Systolic blood pressure, diastolic blood pressure, serum cholesterol, serum uric acid, past history of illness, present illness, body mass index (BMI: weight/height2 (kg/m2)), indices of weight change (the intrapersonal standard deviation of BMI (ISD), the coefficient of variation of BMI (CV), the root mean square error of variation (RMSE) around the slope of BMI vs age, weight change categories (cycler, weight gainer, no changer, etc.), and number of weight cycles (NWC: one cycle is defined as 5% weight loss and 5% weight gain)). Indices were calculated using yearly and five-yearly measurements of weight for analyses. RESULTS: The average RMSE distinguished large cyclers from other weight change categories, while ISD and CV did not. The correlation between ISD and CV was strong and significant. That between RMSE and ISD (or CV) was moderate and significant. Among the weight change categories, no weight change group included many actual weight cyclers. As for the relationship with coronary risk factors, no significant change in risk was noted in cyclers as determined by NWC or weight change category. The top one third of ISD and the top one third of CV was related with elevated risk of "any risk factor,' but at a lower level of significance. CONCLUSION: ISD and CV reflect almost the same aspects of weight change, but the other indices reflect different aspects. When investigating the relationship between coronary risk factors and weight variability (especially, weight cycling) among young adult non-obese men, it is preferable to use weight change patterns such as NWC and weight change categories, or RMSE in conjunction with or in place of CV (or ISD).

Adult↗

Investigation of genetic risk factors associated with alcoholism.

Alcoholism is a multifactorial disease influenced by genetic-environmental interaction. Genetic variation of the receptor may be associated with alcohol dependence due to its modified function in behavioral and physiological responses. In the present study, polymorphic alleles of cholecystokinin B receptor (CCKBR), serotonin 1A receptor (HT1AR) genes, and mitochondrial DNA were analyzed. DNAs were isolated from the blood samples of 112 healthy controls and 106 alcoholics. Genetic variation was detected by SSCP analysis, followed by direct sequencing of polymerase chain reaction product as well as restriction fragment-length polymorphism. Three different mutations were found in the exon 3 sequence of CCKBR: His (CAT) at aa207-->His (CAC) (5.4%), Arg (CGC) at aa215-->His (CAC) (4.5%), and Val (GTG) at aa138-->Met (ATG) (0.9%) in controls. Genotypic distribution of alcoholics was not significantly different with that in controls. A proline (CCG) to leucine (CTG) substitution at amino acid 16 of HT1AR was found in alcoholics (4.5%) and in controls (4.7%). This mutation site of HT1AR was different in comparison with the variants reported by Nakhai et al. (Biochem Biophys. Res. Commun. 210:530-536, 1995). Analysis of the mitochondrial DNA showed that a 491 bp deletion in the sequence of ATPase exists as heteroplasmy in 58% of alcoholics, but not in controls. Heteroplasmic deletion of mitochondrial DNA may be a useful marker for alcohol abuse. Further study is undergoing to elucidate the cause and significance of this deletion in alcoholics.

Alcoholism↗

[Airway hyperresponsiveness and airway mucosal permeability].

The relationship between airway mucosal permeability and airway hyperresponsiveness was examined with tachykinins, their selective antagonists, and superoxide dismutase in male Hartley guinea pigs. In animals with ozone-induced airway inflammation, airway hyperresponsiveness and mucosal permeability increased concurrently but there was a time lag before the increase in airway vascular permeability. To study the role of tachykinins in the increases in mucosal permeability and in hyperresponsiveness, we used a neurokinin-receptor antagonist, CP-96345, and a neurokinin-2 receptor antagonist, SR-48968. CP-96345 had no significant effect, but SR-48968 reduced the increase in airway mucosal permeability; their effects on airway hyperresponsiveness were the opposite of their effects on airway permeability. Tachykinins themselves, both substance P and neurokinin A, significantly increased airway mucosal permeability. Superoxide dismutase, a scavenger enzyme of superoxide, reduced the ozone-induced airway hyperresponsiveness. These data suggest that the factors causing airway hyperresponsiveness differ from those that influence mucosal permeability, but it is possible that these pathophysiologic conditions are caused by the same substances or processes.

Animals↗

Isolation and characterization of novel antimicrobial peptides, rugosins A, B and C, from the skin of the frog, Rana rugosa.

Three antimicrobial peptides were isolated from the skin of Rana rugosa. The major component, designated rugosin A, consisted of 33 amino acid residues and had structural homology (45%) with brevinin-2 of Rana porosa brevipoda. This peptide strongly inhibited the growth of gram-positive bacteria (e.g. Staphylococcus aureus 209P). The second peptide (rugosin B), a minor component, also had 33 amino acid residues, but was less homologous (33%) with brevinin-2. This peptide exhibited a striking antimicrobial activity against both gram-negative (e.g., Escherichia coli NIHJ) and gram-positive bacterial species. The third one, named rugosin C, composed of 37 amino acid residues, exhibited an antimicrobial activity against gram-positive bacteria. All three peptides had an intramolecular disulfide bond at the C-terminus.

Amino Acid Sequence↗

Platelet-activating factor mediates the ozone-induced increase in airway microvascular leakage in guinea pigs.

In the present study, we asked whether platelet-activating factor (PAF) mediates the ozone-induced increase in airway microvascular leakage. To answer this question, we examined the effect of a PAF receptor antagonist on the ozone-induced increase in airway microvascular leakage quantified by the extravasation of Evans blue dye in the guinea pig trachea and main bronchi. Guinea pigs were pretreated with the PAF receptor antagonist, E6123 ((S)-(+)-6-(2-chlorophenyl)-3-cyclopropane-carbonyl-8,11-dimethyl-2,3,4, 5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2- f][1,2,4]triazolo[4,3-a][1,4]diazepine) (0.01, 0.1 and 1.0 mg/kg i.v.) and then exposed to 3 ppm ozone for 30 min. The PAF receptor antagonist significantly reduced the ozone-induced increase in microvascular leakage in a dose-dependent manner in both the trachea and main bronchi. Our results indicate that PAF mediates the ozone-induced increase in airway microvascular leakage. We therefore suggest that PAF may be involved in ozone-induced airway inflammation.

Animals↗

Lack of the expression of EBNA-2 and LMP-1 in T-cell neoplasms possessing Epstein-Barr virus.

We investigated 34 cases of T-cell neoplasm [15 cases of T-cell granular lymphocytic leukemia (T-GLL), 10 cases of T-cell non-Hodgkin's lymphoma (T-NHL), six cases of T-cell chronic lymphocytic leukemia (T-CLL), and three cases of cutaneous T-cell lymphoma] to study their association with Epstein-Barr virus (EBV). In 4 (three T-NHL and one T-GLL) of 34 cases, EBV genome was detected in a single episomal form, while polyclonal EBV-DNA was detected in one (T-NHL) of the remaining cases. All three cases of T-NHL having monoclonal EBV episome showed histologically diffuse large-cell lymphoma and developed leukemic conversion. Phenotypic analysis showed that two of these four cases were CD4+, CD8-, and the remaining two cases were CD4-, CD8+. The cells from all four cases were confirmed to be in T-cell lineage by detecting the rearrangement of T-cell receptor (TCR) beta or gamma chain gene. By reverse transcription-polymerase chain reaction (RT-PCR), EBNA-1 was detected at low levels, and neither EBNA-2 nor LMP-1 were found in any of the three cases examined. Lack of the expression of EBNA-2 and LMP-1 was also confirmed by immunocytochemical staining. The cells of these four cases did not show rearrangement or overexpression of c-myc and bcl-2 genes by Southern and Northern blots, and the mutation of p53 gene was detected in only one patient. These results suggest that other latent gene products of EBV or other cellular oncogenes are involved in the development of Japanese T-cell neoplasm after EBV infection.

Antigens, Viral↗

Binding site in human plasma fibronectin to HL-60 cells localizes in the C-terminal heparin-binding region independently of RGD and CS1.

A 29-kDa monomeric dispase-digestive fragment of human plasma fibronectin has been purified by heparin affinity chromatography. The NH2-terminal sequence was determined as Ala1687-Val-Thr-Thr-Ile-Pro-Ala-Pro. By mass spectrometry the molecular weight was determined to be 30,241.9 with standard deviation of 3.9 amu. Therefore, we defined the C-terminal sequence of the 29-kDa fragment as Arg1957-Lys-Lys-Thr-Gly-Gln-Glu. This indicates that the fragment is composed of 277 amino acids. 125I-fibronectin and the 125I-labeled 29-kDa fragment bound to HL-60 (human acute promyelocytic leukemia) cells in a time-dependent, saturable, and reversible manner. Approximately 120 min was required to reach maximal binding. There were no differences in quantity or rate of binding of labeled fibronectin and 29-kDa fragment at temperatures of 4 degrees, 22 degrees, and 37 degrees C. The number of binding sites per HL-60 cell of fibronectin and the 29-kDa fragment were 140,000 with a Kd of 133 nM and 108,000 with a Kd of 250 nM, respectively. The binding of fibronectin to HL-60 cells was completely inhibited by this fragment, and by the peptides of RGDS and CS1 with IC50s of 3.6, 840, and 670 microM, respectively. Native fibronectin inhibited the direct binding of the 29-kDa fragment to HL-60 cells; however, RGDS peptide, peptide CS1, or two melanoma cell adhesion-promoting domain peptides in this 29-kDa fragment (peptide I; Tyr1906-Val1924, peptide II; Asp1946-Thr1960) did not block this binding. Neither heparitinase nor chondroitinase treatment of cells had any effect on these bindings. These results indicate that the C-terminal cell- and heparin-binding domain of fibronectin mediates HL-60 cell binding by direct interaction independently of RGD, CS1, and melanoma cell adhesion domains in this fragment.

Amino Acid Sequence↗

Juvenile xanthogranuloma with cutaneous and cerebral manifestations in a young infant.

Juvenile xanthogranuloma is usually a self-limiting disease of the skin. Intracranial manifestations are extremely rare. We report the clinico-pathological features of an 8-month-old boy suffering from a gradually enlarging nodule of the chest wall and subsequent epileptic seizures. The subcutaneous tumor and a cerebral subcortical tumor of the left temporal lobe were resected. The histological appearance of both tumors corresponded to juvenile xanthogranuloma and included histiocytes, foamy cells, giant cells, inflammatory cells, and collagen-producing fibroblasts showing a storiform pattern. Immunohistochemical studies demonstrated positivity of the tumor cells for lysozyme, CD68 and myeloid-histiocytic antigen, but not S-100 protein, supporting mono-histiocytic differentiation. This case indicates that juvenile xanthogranuloma should be considered in the differential diagnosis of intracranial "xanthomatous" and histiocytic lesions.

Antibodies↗