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Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 253 records · Page 14Linked to original sources
PubMed1999

Autologous and allogeneic transplantation with peripheral blood CD34+ cells: a pediatric experience.

BACKGROUND AND OBJECTIVE: Peripheral blood stem cells (PBSC) have replaced bone marrow (BM) as the primary form for autologous hematopoietic stem cell transplantation. Furthermore, the use of allogeneic PBSC transplantation is now rapidly expanding and several centers have adopted this procedure. A new strategy in the use of PBSC is positive selection of CD34+ hematopoietic progenitor (CD34+) cells, and indeed large-scale devices for the clinical exploitation of CD34+ cell selection are now commercially available. In the autologous setting, the primary advantage of using CD34+ selected PBSC is reduced tumor cell contamination during PBSC preparation. On the other hand, in the allogeneic setting, CD34+ selection methods are used to reduce the incidence and severity of GvHD. Initial trials of CD34+ selected PBSC transplants have mainly been performed in adult cancer patients, and experience with CD34+ selected PBSC transplantation in pediatric populations is still limited. The purpose of this review is to clarify the status of CD34+ selected PBSC transplantation in the pediatric population. EVIDENCE AND INFORMATION SOURCES: All authors of the present review work in the field of pediatric stem cell transplantation and in a stem cell processing laboratory, and have contributed to original papers published in peer-reviewed journals. The materials examined in the present review include articles and abstracts published in journals covered by the Science Citation Index and Medline. However, since there is still limited experience with CD34+ cell selection in pediatric populations, information on experience in adults will be discussed regarding the CD34+ cell-selection procedures and transplantation. Pediatric experience with transplants with CD34+ selected cells will be presented and discussed primarily based on our own experience. Specific problems related to PBSC mobilization and collection in children will also be discussed. STATE OF THE ART: A review of the literature shows that with current CD34+ selection methods, purity of the CD34+ cell fraction can range from 30% to 90%, and two to three logs of T-cell depletion can be achieved. Tumor cell contamination has not yet been fully evaluated. The clonogenic activity of progenitor cells after CD34+ selection from PB remains high. Transplantation of autologous selected CD34+ cells from PBSC gives prompt and stable engraftment. The long-term therapeutic efficacy should be evaluated with regard to tumor recurrence. Allogeneic CD34+ selected cells successfully engraft immunomyeloablated recipients though a mega-cell dose effect between HLA-matched pairs. The results of allogeneic CD34+ selected cell transplantation from HLA-mismatched donors are, so far, not satisfactory because of the high rate of rejection, severe infectious complications and relapse of the disease. CD34+ selection may also be used as a target of gene therapy, as a source of dendritic cells for cancer immunotherapy and for the treatment of patients with autoimmune disease.

Antigens, CD34↗
PubMed1999

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. Clinical study on pulmonary tuberculosis associated with lung cancer patients].

Sixteen of 758 lung cancer in patients (2.1%) were found to have coexisting pulmonary tuberculosis. Of the above 16 of 758 patients (fifteen men and one woman), 4 of 214 patients (1.9%) were found from 1988 to 1989, and 12 of 544 patients (2.2%) from 1991 to 1994. In six patients, pulmonary tuberculosis and lung cancer were found at the same time by clinical work up. In five cases each, pulmonary tuberculosis preceded lung cancer, and lung cancer preceded pulmonary tuberculosis, respectively. Ten patients had adenocarcinoma, 4 had squamous cell carcinoma, and one each had large cell carcinoma and small cell carcinoma, respectively. Five patients were in stage "II", one in "IIIa", two in "IIIb", and eight in "IV" of clinical stage of lung cancer. As regards extent of pulmonary tuberculosis, one patient was in category "II" of the classification of the Japanese Society for Tuberculosis, 13 were in "III", and two were in "IV". Among 544 lung cancer patients from 1991 to 1994, 9 of 151 patients (6.0%) with a past history of pulmonary tuberculosis, had active pulmonary tuberculosis, and 3 of 393 patients (0.8%) with no history of pulmonary tuberculosis, had active pulmonary tuberculosis (statistically significant; p < 0.005). Five smear-positive patients were transferred to a tuberculosis hospital or a tuberculosis ward, and the remaining 11 patients were treated in isolation in the ward where they were. The efficacy of anti-tuberculous chemotherapy was almost comparable to that in patients without lung cancer. However, prognosis was poor, in line with that of lung cancer. Main discussion was devoted to the reason why the incidence (in association with tuberculosis) of adenocarcinoma exceeded that of squamous cell carcinoma in our present study at variance with the studies of other investigators.

Adenocarcinoma↗
PubMed1999

[Susceptibilities of Enterococcus faecium, PRSP and MRSA to RP59500 and their correlations with those to other drugs].

Investigations on emergence of vancomycin-resistant Enterococcus faecium (VREF) which has recently been attracting attention, especially in the Western countries, have been conducted in Japan. A total of 1,239 isolates of E. faecium were collected from 19 institutions during the period of April 1995 and June 1996, in the purpose of evaluating susceptibilities to variety of antimicrobial agents, including RP59500 and vancomycin (VCM), and detecting vancomycin-resistant genes (van genes). Susceptibilities of penicillin-resistant Streptococcus pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) were also studied. As a result, 2 isolates of E. faecium were found to be moderately resistant to VCM showing MIC of 8 micrograms/ml though the final identification in species level and the detection of van genes by PCR method have not been completed. On the other hand there detected no MRSA nor PRSP showing moderately resistant or resistant to VCM. It was concluded that RP59500 and VCM possessed favorable activity against clinically isolated E. faecium, PRSP and MRSA. Among other species of enterococci, moderately resistant strains to VCM showing MIC of 8 micrograms/ml were detected; 10 isolates of E. gallinarum, 4 of E. casseliflavus and 2 of E. flavescens. In those isolates, vanC1 and vanC2 were detected by PCR, and vanB was also detected in a isolates of E. gallinarum simultaneously.

Anti-Bacterial Agents↗
PubMed1999

Multiple myeloma evaluated with 201Tl scintigraphy compared with bone scintigraphy.

UNLABELLED: The purpose of this study was to investigate the clinical usefulness of 201Tl chloride scintigraphy in the diagnostic evaluation of 20 patients with multiple myeloma (19/20 patients) or extramedullary plasmacytoma (1/20 patients) in comparison with bone scintigraphy. METHODS: Both 201Tl and bone scintigraphy were performed to obtain planar images on the same instrument. RESULTS: 201Tl scintigraphy showed increased uptake in 15 of 20 patients (75%) and was negative in 5 of 20 patients (25%). In addition, 201Tl scintigraphy of multiple myeloma was more useful in detecting the lesions in 11 of 17 patients and less useful in 6 of 17 patients than bone scintigraphy. CONCLUSION: The combination of 201Tl and bone scintigraphy, compared with bone scintigraphy alone, shows promise in more accurately diagnosing multiple myeloma.

Bone Neoplasms↗
PubMed1999

[Significance and prospective view of microbiological examination concerning the guidelines for pneumonia management].

In Japan, the guidelines for the management of pneumonia in adults will be established in about tow years followed by Europe and the USA. The significance and prospective view of microbiological examination concerning the guidelines for pneumonia management in Japan are discussed here. Concerning the management of acute pneumonia, the differential diagnosis between bacterial pneumonia and atypical pneumonia is necessary, but the present system of microbiological examination using culture of microbials and antimicrobial susceptibility testing is time-consuming. A quick reporting system of sputum gram-staining and molecular diagnosis in microbiological laboratories will greatly contribute to the management of bacterial pneumonia and atypical pneumonia, respectively. This quick reporting system should be combined with automatic systematization of microbiological examination in laboratories in the future.

Adult↗
PubMed1999

[Goodpasture's syndrome initially presenting with alveolar hemorrhage].

A 17-year-old man was admitted to our hospital because of exertional dyspnea, fever, and hemoptysis. Chest X-ray films disclosed diffuse alveolar infiltrates and patchy shadows in both lungs. Laboratory data included a hemoglobin level of 6.7 g/dl and white blood cell count of 8,100/microliter. Urinalysis revealed microscopic hematuria with RBC cast. Bronchoalveolar lavage fluid from the right middle lobe bronchus was bloody. Anti-GBM antibodies were detected at low levels in serum (10 EU/ml) by ELISA procedures. Renal and lung biopsies were performed. Immunofluorescent studies revealed linear deposits of IgG along glomerular basement membrane of the kidney, but not in alveolar walls of the lung. This case fulfilled the criteria for Goodpasture's syndrome. The patient was treated with methylprednisolone (1,000 mg/day, for 3 days) and plasma exchange (for 2 days), and demonstrated a dramatic improvement in his clinical condition and chest X-ray findings. We were unable to identify autoantibodies to the NC domain of the alpha 3 chain of type IV collagen. Another conformational epitope may play a role in the disease.

Adolescent↗
PubMed1999

Detection of annexin I and IV and haptoglobin in bronchoalveolar lavage fluid from calves experimentally inoculated with Pasteurella haemolytica.

OBJECTIVE: To determine whether annexins or haptoglobin could be detected in bronchoalveolar lavage (BAL) fluid specimens obtained from calves experimentally inoculated with Pasteurella haemolytica. ANIMALS: Twelve 2- to 3-month-old male Holstein calves. PROCEDURE: Pasteurella haemolytica was inoculated into the right lung lobes of each of 6 calves. Six other calves received vehicle alone and were used as control calves. Specimens of BAL fluid were obtained from 3 control and 3 inoculated calves 1 day after inoculation and from the other calves 2 days after inoculation. The amount of annexins I, II, IV, and VI, and haptoglobin in BAL fluid specimens was examined by use of immunoblot analysis. RESULTS: Annexins I and IV were detected in BAL fluid specimens obtained from the right lung lobes of each of the inoculated calves, but annexins II and VI were not. Annexin I also was found in BAL fluid specimens obtained from the left lung lobes of each inoculated calf and from left and right lung lobes of the control calves. By comparison, detection of annexin IV was essentially limited to the right lung lobes of inoculated calves. Haptoglobin was detected in some, but not all, BAL fluid specimens from the right lung lobes of inoculated calves, and its detection in BAL fluid was associated with serum proteins such as albumin. CONCLUSIONS AND CLINICAL RELEVANCE: Annexin IV was detected most specifically in response to inoculation of P haemolytica. This protein could be used as a marker for inflammatory pulmonary disease caused by P haemolytica.

Animals↗
PubMed1999

Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

BACKGROUND: The present study was designed to evaluate the association of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP) gene and lung resistance protein (LRP) gene expression (mRNA levels) with risk factors such as phenotype, age and leukocyte count in newly diagnosed childhood acute lymphoblastic leukemia, because biological mechanisms contributing to risk factors were not known. METHODS: Expression of the MDR1, MRP and LRP genes in leukemic cells from 40 pediatric patients was quantitated using the reverse transcriptase polymerase chain reaction method. The associations of expression of these genes with age and leukocyte count, which are known as risk factors for acute lymphoblastic leukemia (ALL), were analyzed. Moreover, the associations with clinically classified risk-related groups (high-risk ALL and low-risk ALL) were also investigated. RESULTS: No positive correlations between expression of these genes and age or leukocyte count were found. The expression of these genes was not different among clinically classified risk-related groups. CONCLUSIONS: Expression (mRNA levels) of the MDR1, MRP and LRP genes did not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

Adolescent↗
PubMed1999

[The influence of L-triiodothyronine on the action of desipramine on beta and serotonin 2A receptor, monoamines in the rat brain].

The co-administration of thyroid hormone and antidepressants is often useful in the treatment of refractory depression. The aim of this study is to clarify the anti-depressive mechanisms of repeated co- administration of thyroid hormone (T3) and desipramine (DMI) in the rat brain. Forced swimming test, open-field test, monoamine contents, beta receptor, and serotonin (5HT)2A receptor were compared in four experimental groups (control, T3, DMI, DMI+T3). In the forced swimming test, the (DMI+T3) group showed a significantly decreased immobility time compared with that of the control group. The noradrenaline (NA) content in the prefrontal cortex was highest in the (DMI+T3) group. Although beta receptor was not altered in any brain region in the (DMI+T3) group, 5HT2A receptor was significantly decreased, and the dopamine (DA) turnover rate was significantly increased in the prefrontal cortex. This study suggests that the addition of T3 enhanced the action of DMI alone on the monoaminergic system in the prefrontal cortex.

Animals↗
PubMed1999

[In vitro activity of biapenem (BIPM) against clinically isolated respiratory pathogens in 1996-1998].

The in vitro antibacterial activity of biapenem (BIPM), a new carbapenem antibiotic, was compared with those of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and piperacillin (PIPC) against 280 isolates of 9 respiratory pathogens. The MIC90s of biapenem (BIPM) for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Haemophilus influenzae were 0.12, 32, 0.25, 0.06, 4 and 8 micrograms/ml, respectively. In comparison with other antibiotics, the activity of biapenem (BIPM) for P. aeruginosa was as potent as meropenem (MEPM), but for H. influenzae it was slightly less than those of other antibiotics, and for other respiratory pathogens it was as potent as those of other antibiotics. The MIC90s of biapenem (BIPM) for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens were 0.06, 1, 1, 0.5 microgram/ml, respectively, and which were equal to or somewhat lower than those of other antibiotics. Biapenem (BIPM) showed strong activity against Gram-positive and Gram-negative pathogens, especially P. aeruginosa in general. Based on these results, biapenem (BIPM) is seemed to be highly useful antibiotic for the treatment of respiratory infections with several organism.

Bacteria↗
PubMed1998

Restricted photorelease of biologically active molecules near the plasma membrane.

An evanescent wave of ultraviolet light was successfully used to release biologically active molecules from caged compounds in living cells. The evanescent wave was generated by the total internal reflection in a limited region near the plasma membrane attached to the illuminated interface. At first, the photolysis efficiency of the evanescent wave of ultraviolet laser light was studied using caged glutamic acid in vitro. Then, caged Ca2+ introduced in the living cultured cell was similarly photolyzed by the evanescent wave and the resulting elevations of the concentration of intracellular Ca2+ in the proximity of the plasma membrane and in the cytosol were observed with a simultaneously introduced fluorescent calcium indicator. Inositol trisphosphate can also be photoreleased near the plasma membrane, which enables study of the temporal and spatial pathways of signal transduction. The method developed here provides a useful tool for studying signal transduction near the plasma membrane in a living cell.

Aniline Compounds↗
PubMed1998

Transamination as a side-reaction catalyzed by alanine racemase of Bacillus stearothermophilus.

The pyridoxal form of alanine racemase of Bacillus stearothermophilus was converted to the pyridoxamine form by incubation with its natural substrate, D- or L-alanine, under acidic conditions: the enzyme loses its racemase activity concomitantly. The pyridoxamine form of the enzyme returned to the pyridoxal form by incubation with pyruvate at alkaline pH. Thus, alanine racemase catalyzes transamination as a side function. In fact, the apo-form of the enzyme abstracted tritium from [4'-3H]pyridoxamine in the presence of pyruvate. A mutant enzyme containing alanine substituted for Lys39, whose epsilon-amino group forms a Schiff base with the C4' aldehyde of pyridoxal 5'-phosphate in the wild-type enzyme, was inactive as a catalyst for racemization as well as transamination. However, when methylamine was added to the mutant enzyme, it became active in both reactions. These results suggest that the epsilon-amino group of Lys39 participates in both racemization and transamination when catalyzed by the wild-type enzyme.

Alanine Racemase↗
PubMed1998

Marginal benefit/disadvantage of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in children: results of a prospective randomized trial. The Japanese Cooperative Study Group of PBSCT.

In this prospective trial, a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor (G-CSF) treatment in accelerating hematopoietic recovery after PBSCT. The diagnosis included acute lymphoblastic leukemia (ALL) (n = 27), neuroblastoma (n = 29), and miscellaneous solid tumors (n = 18). Eligibility criteria included (1) primary PBSCT, (2) chemotherapy-responsive disease, and (3) collected cell number >1 x 10(5) colony-forming unit-granulocyte-macrophage (CFU-GM)/kg and >1 x 10(6) CD34(+) cells/kg patient's body weight. After applying the above criteria, 11 patients were excluded due to disease progression before PBSCT (n = 6) or a low number of harvested cells (n = 5), leaving 63 patients for analysis; 32 patients in the treatment group (300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT) and 31 in the control group without treatment. Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine (MCNU, 450 mg/m2), cytosine arabinoside (16 g/m2), etoposide (1.6 g/m2), and cyclophosphamide (100 mg/kg) for patients with ALL, and the Hi-MEC regimen using melphalan (180 mg/m2), etoposide (1.6 g/m2), and carboplatinum (1.6 g/m2) for those with solid tumors. Five patients (two in the treatment group and three in the control group) were subsequently removed due to protocol violations. All patients survived PBSCT. The median numbers of transfused mononuclear cells (MNC), CD34(+) cells, and CFU-GM were, respectively, 4.5 (range, 1 to 19) x 10(8)/kg, 8.0 (1.1 to 25) x 10(6)/kg, and 3.7 (1.2 to 23) x 10(5)/kg in the treatment group (n = 30) and 2.9 (0.8 to 21) x 10(8)/kg, 6.3 (1.1 to 34) x 10(6)/kg, and 5.5 (1.3 to 37) x 10(5)/kg, respectively, in the control group (n = 28), with no significant difference. After PBSCT, the time to achieve an absolute neutrophil count (ANC) of >0.5 x 10(9)/L in the treatment group was less than that in the control group (median, 11 v 12 days; the log-rank test, P =.046), although the last day of red blood cell (RBC) transfusion (day 11 v day 10) and the duration of febrile days (>38 degrees C) after PBSCT (4 v 4 days) were identical in both groups. However, platelet recovery to >20 x 10(9)/L was significantly longer in treatment group than control group (26 v 16 days; P =.009) and >50 x 10(9)/L tended to take longer in the treatment group (29 v 26 days; P =.126), with significantly more platelet transfusion-dependent days (27 v 13 days; t-test, P =.037). When patients were divided into two different disease cohorts, ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups, while differences were seen in those with solid tumors. We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets. We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered.

Adolescent↗
PubMed1998

Frequent aberration of FHIT gene expression in acute leukemias.

We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent or markedly decreased. Only abnormal short bands were detected in 30% of the ALL cases and 5% of the AML cases. Eighteen of 19 abnormal transcripts had the same fusion of exons 2-7, and all lacked the starting codon in exon 5. No obvious normal-sized PCR products were detected in cases exhibiting abnormal transcripts. These findings suggest that the expression of functional FHIT protein was lost in the majority of ALL (76%) and AML (60%) cases. Differential quantitative PCR of exons 3-9 of the FHIT gene and RT-PCR of the PTPRG gene, which is centromeric to the FHIT gene, showed the presence of the target sequences. Fluorescence in situ hybridization analysis using probes covering exons 5 and 8 revealed no difference in the signal patterns between leukemia and normal cells, showing one or two signal doublets in more than 90% of nuclei, and indicated that gross segments of the FHIT gene were not homozygously deleted in these cases. A small number of transcripts with an aberrant fusion between exons 2 and 7 were detected by RT-PCR in the bone marrow cells from four healthy individuals. Granulocytes, lymphocytes, and monocytes in the bone marrow cells of a healthy individual contained transcripts with the same fusion. This unique fusion of exons 2 and 7 might be preferentially seen in either neoplastic or normal hematopoietic cells, regardless of their lineage. The finding that FHIT expression was abolished in the majority of leukemia cases might support the hypothesis that the FHIT gene acts as a tumor suppressor, at least in leukemia.

Acid Anhydride Hydrolases↗
PubMed1998

NMDA induced glutamate release from the suprachiasmatic nucleus: an in vitro study in the rat.

The suprachiasmatic nucleus (SCN) has been identified as a pacemaker for mammalian circadian rhythms. Excitatory amino acid receptors, especially N-methyl-D-aspartate (NMDA) receptors, have been considered to play an important role in the transmission of light information from the retina to the circadian clocks in the SCN. In the present study, we showed that application of NMDA at circadian time (CT) 12-15 induced significant glutamate release from the SCN region in vitro. The NMDA-induced glutamate release was blocked by co-application of the NMDA receptor antagonist MK-801, but not by that of tetrodotoxin. These results suggested that glutamate stimulated its own release by activating NMDA receptors. This NMDA-induced glutamate release through NMDA receptor-mediated mechanisms might be involved in NMDA-induced potent phase shifts.

Animals↗