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Biomedical subjects

T Naruse

Publications and source records attributed to T Naruse.

At least 73 records · Page 4Linked to original sources

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Adolescent↗

Successful low-dose cytosine arabinoside treatment in a patient with acute leukemia from idiopathic myelofibrosis.

We report a 63-year-old male with acute leukemia developed from idiopathic myelofibrosis. Cytogenetic analysis revealed chromosomal abnormalities; 46,XY,t(3;21)(q21;q22) del(20q). Intensive chemotherapies [combination of adriamycine/vincristine/prednisolone, or idarubicine/cytosine arabinoside (Ara-C)] were unsuccessful. The patient was then treated with continuous intravenous low-dose Ara-C because of his poor physical condition and showed marked hematological improvement. Leukemic cells disappeared from the peripheral blood and the segmented neutrophil count recovered. The dysplastic morphology observed in the segmented neutrophils suggests that the recovery of the neutrophils has resulted mainly from the differentiation activity of Ara-C.

Acute Disease↗

Role of autoantibodies against tubular brush border antigens in tubulointerstitial nephritis associated with Heymann nephritis.

Previous studies have shown that a rat experimental model of membranous nephropathy (Heymann nephritis) is often associated with tubulointerstitial changes. Although antibody-dependent tubular injuries have been proposed in this model, precise mechanisms have been ill-defined. In the present report, we established a model of acute tubulointerstitial nephritis (TIN) by injecting puromycin aminonucleoside (PAN) to Wistar rats which had been immunized with tubular antigens (Tub-Ag). In this model, TIN developed 4 weeks after Tub-Ag immunization when rats had a high titer of circulating anti-Tub-Ag antibodies and began to excrete massive proteinuria. Deposits of immunoglobulins along tubular brush borders were also demonstrated. Rats receiving either Tub-Ag or PAN alone failed to develop TIN during this relatively acute phase. These results suggest that anti-Tub-Ag antibodies excreted into the urine play a role in developing TIN in this model.

Animals↗

[Autoimmune neutropenia accompanied by Tolosa-Hunt syndrome].

A 47-year-old woman presented with severe neutropenia accompanied by diplopia and orbital pain. Her bone marrow was normal except for the absence of segmented neutrophils. Because the administration of granulocyte colony-stimulating factor (G-CSF) at a dose of 1 microgram/kg/day was not sufficiently effective and neutropenia developed, the patient was admitted to our hospital. Physical examination revealed painful ophthalmoplegia and hypoalgesia in the first region of trigeminal nerve, suggestive of Tolosa-Hunt syndrome. Severe neutropenia was observed in both peripheral blood and bone marrow, together with mild anemia and thrombocytopenia. The life span of red cells and platelets was shortened. High PAIgG levels, a positive Coombs test, and a positive test for anti-NA1 antibody suggested that blood cells were being destroyed by an autoimmune mechanism. Corticosteroid hormone therapy preceded by the administration of G-CSF at 5 micrograms/kg/day was effective for both neutropenia and in improving the patient's neurological findings.

Autoimmune Diseases↗

KEMRI Hep-cell II hepatitis B surface antigen screening kit.

BACKGROUND: Kenya is a high hepatitis B virus (HBV) endemic zone. Prevention of HBV transmission by transfusing safe blood is necessary. Kits for screening hepatitis B surface antigen (HBsAg) are usually imported and are expensive. Hence it has been difficult to screen donated and patient blood samples all over Kenya. OBJECTIVE: To produce a HBsAg screening kit locally in order to be able to screen donated and patient blood samples all over Kenya. DESIGN: A laboratory based study. SETTING: Centre for Virus Research (CVR), Kenya Medical Research Institute (KEMRI), Nairobi. METHOD: Purified HBsAg from plasma of carriers obtained from National Public Health Laboratories Services (NPHLS) was used to minimise guinea pigs to produce antihepatitis B (anti HBs) antibody. The anti HBs was then used to sensitise sheep red blood cells (SRBC). The final product was freeze dried (lyophilised) and its sensitivity and specificity was compared with other commercial kits. RESULTS: The sensitivity and specificity of KEMRI Hep-cell II was found to be 98% and 99%, respectively. The kit was found to be stable and potent for one year whether kept 4 degrees C, 37 degrees C or room temperature. CONCLUSION: KEMRI Hep-cell II was successfully produced locally. The sensitivity and specificity were comparable to other commercial kits. The kit was stable and potent for one year between temperature of 4 degrees C and 37 degrees C. The kit required only simple apparatus to carry out the test hence it can be used anywhere in Kenya. It was also cheap and affordable.

Carrier State↗

Expression and functional analysis of a hemopoietic progenitor antigen, NJ-1 (114/A10), in the megakaryocytic lineage.

To analyze the functions of molecules expressed in hemopoietic progenitor cells, we obtained several monoclonal antibodies by immunizing Wistar rats with antigens from a murine immature leukemic cell line, DA-1. Here, we characterize one antibody designated NJ-1, which recognizes a 145-kd molecule, and identify the cDNA encoding the NJ-1 antigen by retrovirus-mediated expression cloning. Sequence analysis of the cDNA reveals that it is identical to a previously reported cDNA encoding a surface molecule of 573 amino acids recognized by monoclonal antibody 114/A10. Our studies show that expression of NJ-1 antigen is upregulated in a murine megakaryoblastic cell line, L8057, when it differentiates into a megakaryocytic lineage in response to 12-O-tetradecanoyl phorbol-13-acetate. Overexpression of NJ-1 antigen in L8057 cells inhibits cell adhesion to fibronectin, suggesting that it may act as a negative regulator of cell adhesion in the megakaryocytic lineage.

Animals↗

Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs.

The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. Moguisteine (2.5-10 mg/kg, intravenously, i.v.) reduced the cough reflex induced by 7.5% citric acid aerosol in a dose-dependent manner, with an ED50 value of 0.55 mg/kg. Both i.v. (0.5-4 mg/kg) and intracerebroventricular (i.c.v., 5-20 microg) injection of codeine dose dependently inhibited the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve; the ED50 values were 0.91 mg/kg and 7.90 microg, respectively. The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.

Aerosols↗

Integrin-mediated signal transduction in cells lacking focal adhesion kinase p125FAK.

We have previously shown that integrin-dependent tyrosine phosphorylation of p130Cas (Cas) could be induced in a mouse fibroblast cell line that does not express focal adhesion kinase p125FAK (FAK). By analyzing FAK-deficient (FAK-/-) cells transiently expressing Cas mutant proteins, we demonstrate here that the Src homology 3 (SH3) domain of Cas is indispensable for adhesion-mediated Cas phosphorylation in this mutant cell line. While the FAK directly binds to Cas-SH3, our findings imply that SH3-binding molecule(s) other than FAK might regulate Cas phosphorylation, at least in FAK-/- cells. In this regard, we observed that FAK-/- cells expressed cell adhesion kinase beta (CAKbeta), a protein tyrosine kinase of the FAK subfamily. CAKbeta expressed by FAK-/- cells was associated in vivo with Cas in a Cas-SH3-dependent manner. Moreover, integrin stimulation induces tyrosine phosphorylation of CAKbeta in FAK-/- cells. Thus, our results suggest that CAKbeta contributes to integrin-mediated signal transduction in place of FAK in FAK-deficient cells.

Animals↗

Effects of a novel non-steroidal anti-inflammatory drug (M-5011) on bone metabolism in rats with collagen-induced arthritis.

The effects of a novel non-steroidal anti-inflammatory drug (NSAID), d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid: M-5011, and other NSAIDs (indomethacin, zaltoprofen and tiaprofenic acid) on bone metabolism in Dark Agouti (DA) strain rats with collagen-induced arthritis were evaluated. M-5011 (1.5 and 4.5 mg/kg) and other NSAIDs (1.5 mg/kg) were administered orally once a day from day 14 to day 35 after collagen immunization. In arthritic rats, paw volume and serum levels of anti-type II collagen antibody were increased on day 21 compared to those in non-immunized rats. M-5011 (4.5 mg/kg), indomethacin and zaltoprofen tended to prevent this increase in paw volume. Elevated urinary pyridinoline and deoxypyridinoline levels were found on days 28 and 35 in arthritic rats. M-5011 (4.5 mg/kg) also tended to prevent the increase in urinary pyridinoline level on day 28, but none of the other NSAIDs affected urinary deoxypyridinoline levels. Bone mineral densities in the hindpaw and vertebrae were also decreased in arthritic rats. M-5011 and tiaprofenic acid prevented this decrease in vertebral bone mineral density. These findings indicate that M-5011 partially inhibits the generalized bone loss accompanying the development of collagen-induced arthritis in rats.

Absorptiometry, Photon↗

Coincidental occurrence of pernicious anemia and mycosis fungoides in two elderly males.

We experienced two rare cases of pernicious anemia that presented in the course of mycosis fungoides in elderly males. Pernicious anemia has recently been reported to be caused by autoimmune gastritis that produces autoantibodies to gastric parietal cells and intrinsic factor. Immunological abnormalities in mycosis fungoides are reported to induce autoimmune diseases (i.e., autoimmune hemolytic anemia, anti-phospholipid antibody syndrome, arthritis, myasthenia gravis, necrotizing vasculitis, and vitiligo); the pernicious anemia in our two patients may have been closely related to the mycosis fungoides.

Aged↗

Sulfite is released by human neutrophils in response to stimulation with lipopolysaccharide.

Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways. Using a simple and sensitive assay for sulfite concentration in biological fluids, we demonstrate herein that human neutrophils released significant amounts of sulfite (1.0 nmol/h/10(7) cells) in response to lipopolysaccharide (LPS), a major component of bacterial endotoxin. A large proportion of the sulfite release by neutrophils was dependent on inorganic sulfate contained in culture media, suggesting production via the sulfate reducing pathway in this response. We also show that glucocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils. Given the well-known antimicrobial activities of sulfite, our results suggest that sulfite acts as a neutrophil mediator of host defense. A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in vivo administration of LPS is associated with a marked increase in the serum concentration of sulfite in Wistar rats. Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility to bacterial infection commonly associated with the administration of these drugs.

Animals↗

Tubulointerstitial mast cell infiltration in glomerulonephritis.

Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis. Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3 cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA) nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r=0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury.

Adolescent↗

Fulminant, CMV-associated, haemophagocytic syndrome following unrelated bone marrow transplantation.

We report a case of haemophagocytic syndrome (HPS) occurring after allogeneic bone marrow transplantation (BMT) for acute promyelocytic leukaemia (APL) in a patient in fourth complete remission (CR). Anti-cytomegalovirus (CMV) antibody (Ab) was negative in this patient before BMT. BMT was performed from an HLA-identical unrelated donor who was positive for CMV Ab. After bone marrow engraftment and haematological recovery, severe acute graft-versus-host disease (GVHD) developed. This patient was treated with methylprednisolone in addition to cyclosporin A (CsA). Acute GVHD showed partial improvement, but CMV antigenaemia was observed. Despite administration of gancyclovir and immunoglobulin, CMV antigenaemia showed no improvement and HPS developed. As no other infections or malignancies were observed, we suspect that CMV infection was the trigger for development of HPS.

Adult↗

Antitumor effect of oxycellulose as a hemostatic during operation.

Oxycellulose, a hemostatic agent used in operation showed antitumor effect in vitro on a murine hepatic cell carcinoma (MH 134), a murine fibrosarcoma (Meth A) and a murine colon carcinoma (Colon 26). The effect was also confirmed in vivo by the survival of mice inoculated with Meth A or MH 134. Eighty milligrams per mouse of this agent, however, showed a toxicity rather than an antitumor effect. The antitumor effect of oxycellulose on Meth A did not compare with that of etoposide or mitomycin C in vivo. The antitumor effect on MH 134 was equal to that of etoposide but not mitomycin C. Oxycellulose inhibited tritium thymidine uptake into Colon 26 cells to the same extent as 5-fluorouracil and mitomycin C and it caused 51Cr-labelled Colon 26 cells but not from 5-fluorouracil or mitomycin C. Oxycellulose decreased a larger number of viable tumor cells than 5-fluorouracil or mitomycin C when the tumor cells were incubated for 24 hours at 37 degrees C. DNA histogram with MH 134 cells showed oxycellulose decreased a ratio of tumor cells in S-phase. These results suggest that the antitumor effect of oxycellulose is cytocidal and phase-specific.

Animals↗

99Tcm-labelled chimeric human/mouse anti-granulocyte antibody bone marrow scintigraphy: a preliminary clinical study.

Bone marrow scintigraphy using 99Tcm-labelled chimeric anti-granulocyte antibody (anti-NCA-95) was performed in 17 patients with haematological disorders and skeletal metastases. Chimeric anti-NCA-95 antibody (chNCA95 Ab, 0.2 mg) labelled with 444 MBq 99Tcm was administered to obtain bone marrow images 4 h post-injection. One week later, an 111In-chloride bone marrow scan was performed on nine patients with haematological disorders. Lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B) uptake ratios were calculated for each scan. In six patients with suspected skeletal metastases, 99Tcm-HMDP bone scans were performed. No patient had any adverse reaction or any immune reaction over 20 weeks. In the patients with haematological disorders, the L/B and I/B ratios of the 99Tcm-chNCA95 Ab scan were 3.41 +/- 0.90 and 1.23 +/- 0.31, whereas those of the 111In-chloride scan were 1.58 +/- 0.32 and 1.00 +/- 0.32, respectively. In assessing findings of irregular central bone marrow uptake and peripheral expansion of the bone marrow, the 99Tcm-chNCA95 Ab scan was much better than the 111In-chloride scan. In the six patients with suspected skeletal bone metastases, three true-positive and two true-negative results were observed. This preliminary study has revealed that 99Tcm-chNCA95 Ab scanning is safe and useful in the diagnosis of haematological disorders and skeletal metastases.

Adult↗

HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303.

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.

Amino Acid Sequence↗

[Clinical efficacy of fosfomycin in combination with sulbactam/cefoperazone in the treatment of severe infections complicated to blood dyscrasia. Working Group of Kanto Combination Therapy for FOM + SBT/CPZ].

In the treatment of severe infections complicated to blood dyscrasia, the efficacy and usefulness of fosfomycin (FOM) in combination with sulbactam (SBT)/cefoperazone (CPZ) were compared between patients receiving FOM in the first followed by SBT/CPZ (Group A) and those receiving both drugs simultaneously (Group B). The following results were obtained. 1. The efficacy rate was 56.3% for Group A and 47.9% for Group B, with no significant difference. 2. The efficacy for patients suspected of the presence of septicemia, the efficacy rate was 57.9% for Group A and 54.3% for Group B, with no significant difference. 3. As for underlying disease, patients with acute myelogenous leukemia were most prevailing. In these patients, the efficacy rate was 57.1% for Group A and 27.3% for Group B, with no statistically significant difference. However, the efficacy rate tended to be higher in Group A. 4. The administration of antibiotics was effective to restore the neutrophil count to 501/microliters or higher in 77.8% and 45.5% of the cases for Groups A and B, respectively, with significantly higher efficacy for Group A. 5. In the safety evaluation a total of 115 cases were included. Side effects and laboratory abnormalities were seen in 3 cases each, but none of them were serious in degree. From these results, it was confirmed that the combination therapy consisting of administration of FOM followed by SBT/CPZ with some interval is effective for severe infections complicated to blood dyscrasia.

Anti-Bacterial Agents↗