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Biomedical subjects

J Tanabe

Publications and source records attributed to J Tanabe.

At least 37 records · Page 2Linked to original sources

Allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin for treatment of graft failure after allogeneic bone marrow transplantation.

A 43-year-old female with AML-M1 developed late graft failure 4 months after her first allogeneic bone marrow transplant. The patient then underwent a second transplant with peripheral blood progenitor cells obtained from the same HLA-identical brother. The donor peripheral blood progenitor cells were mobilized with granulocyte colony-stimulating factor (10 micrograms/kg daily s.c. for 6 days). The patient received horse anti-thymocyte globulin alone (15 mg/kg per day for 5 days) as the conditioning regimen. Rapid hematopoietic recovery followed a sustained engraftment. The time to reach 0.5 x 10(9)/l neutrophils and 25 x 10(9)/l platelets was 10 and 12 days, respectively. Cytogenetic analysis of bone marrow performed on day +20 demonstrated a 46XY karyotype of donor origin. There was no acute graft-versus-host disease. The patient remains in complete remission with a karnofsky score of 90% 5 months after peripheral blood progenitor cell transplantation. To treat graft failure after allogeneic bone marrow transplantation, allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin alone should be considered as a feasible alternative to marrow transplant.

Adult↗

[Nosocomial pneumonia experienced in a community hospital].

To clarify the characteristic features of nosocomial pneumonia in a community hospital, we performed a clinical analysis of 147 patients (155 episodes) with nosocomial pneumonia. The following results were obtained. 1, Regarding the risk factors for nosocomial pneumonia, factors such as the patient whose age was over 65 years, a duration of admission of over one month, performance status 4 and underlying respiratory diseases associated with the appearance of nosocomial pneumonia. 2, The causative microorganism isolated from the sputum of the patient with nosocomial pneumonia was frequently a multi-drug resistant microorganism such as Methicillin-resistant Staphylococcus aureus (MRSA). 3, regarding treatment, although several antibiotics were administered for a long time, mechanical ventilation was used on 31% of the patients, and steroid pulse therapy was carried out on 24%. The clinical efficacy was poor with a 50% mortality rate. The reason why treatment of nosocomial pneumonia was difficult is thought to be been related to the general condition of these inpatients and to the appearance of a multi-drug resistant, polymicrobial microorganisms.

Adult↗

[Clinical analysis of patients with severe pneumonia requiring mechanical ventilation].

To clarify the clinical features and select the appropriate antibiotic therapy for patients with severe pneumonia requiring mechanical ventilation, we performed a clinical analysis of 65 patients with this condition. The following results were obtained. The majority of the patients were elderly males, whose performance status was poor (PS 2.2) and who had an underying disease. Abnormal physical signs included tachypnea, tachycardia and consciousness disturbance. Abnormal laboratory findings included hypoalbuminemia, and liver and renal dysfunction. The causative microorganisms were isolated from half of these patients. A number of antibiotics were administered and steroid pulse therapy was also performed for half of these patients. Nevertheless the prognosis was poor because the percentage of deaths was high (50.8%).

Adult↗

[Clinical analysis of patients with nosocomial pneumonia during mechanical ventilation (so-called ventilator-associated pneumonia)].

To clarify the clinical features of nosocomial pneumonia during mechanical ventilation (ventilator-associated pneumonia) and to select the appropriate antibiotic therapy for patients, we performed a clinical analysis of 19 patients (26 episodes) with this condition. The following results were obtained. 1, The average age of the patients was 68 years old (male 16, female 3). 2, VAP occurred three times in 2 cases, twice in 3 cases, and once in 14 cases. 3, The duration of mechanical ventilation was from 7 days to 11 years and 5 months (the average was 2.1 years). 4, The microorganism isolated from the aspiration sputum of the VAP patients was Pseudomonas aeruginosa frequently, but it was difficult to determine whether this microorganism was the causative microorganism. Ten strains of Staphylococcus aureus (MRSA seven strains and MSSA three strains) were newly isolated at the same time as VAP and especially in the cases in which these were thought to be causative microrganisms, all the patients died within a short time. 5, Antibiotics were clinically effective for 53.8% of all the VAP patients and carbapenem antibiotics (for example, IPM/CS) were also used for the effective group. 6, Regarding the risk factors for VAP, factors such as the duration of mechanical ventilation, the existence of chronic obstructive pulmonary disease, a hyponutritional state, prior antibiotics, aspiration of gastric contents, histamine-type-2 receptor antagonist, and multiple organ failure showed significant differences and were suspected to be associated with the appearance of VAP.

Adult↗

Induction of neutrophil chemotactic factor production by staurosporine in rat peritoneal neutrophils.

1. Incubation of rat peritoneal neutrophils in medium containing various concentrations of staurosporine (6.4-64 nM) increased the neutrophil chemotactic activity in the conditioned medium in a time- and concentration-dependent manner. 2. Separation of the neutrophil chemotactic activity in the conditioned medium by isoelectric focusing revealed that staurosporine (64 nM) stimulated the production of basic (pH > 8) neutrophil chemotactic factors, while TPA (12-O-tetradecanoylphorbol 13-acetate, 49 nM) stimulated the production of both basic (pH > 8) and acidic (pH 5) neutrophil chemotactic factors. 3. Determination by immunoassay of cytokine-induced neutrophil chemoattractant (CINC)-1, -2 alpha, -2 beta and -3 in the conditioned medium at 4 h revealed that staurosporine (64 nM) and TPA (49 nM) strongly stimulated the production of CINC-3 (staurosporine, 133.0 +/- 3.8; TPA, 26.7 +/- 1.0; control, 0.32 +/- 0.01 ng ml-1, means +/- s.e.mean from four samples) compared to CINC-1 (staurosporine, 55.0 +/- 1.2; TPA, 12.2 +/- 0.3; control, 0.56 +/- 0.01 ng ml-1), and CINC-2 alpha (staurosporine, 1.09 +/- 0.03; TPA, 0.90 +/- 0.02; control, < 0.10 ng ml-1). CINC-2 beta was below the detectable amount (< 0.078 ng ml-1). 4. The level of CINC-3 mRNA in the peritoneal neutrophils was determined by reverse transcription-polymerase chain reaction. Staurosporine (64 nM) and TPA (49 nM) enhanced the level of CINC-3 mRNA time-dependently, but had no effect on GAPDH mRNA levels. 5. Production of staurosporine-induced neutrophil chemotactic factor was inhibited by the protein kinase C inhibitors, H-7 (IC50, 12.3 microM), calphostin C (IC50, 0.77 microM) and Ro 31-8425 (24.3% inhibition at 10 microM), and by the tyrosine kinase inhibitor, genistein (IC50, 68.5 microM). Production of TPA-induced neutrophil chemotactic factor was also inhibited by both inhibitors. 6. Both the staurosporine- and the TPA-induced increase in CINC-3 mRNA levels were suppressed by H-7 and genistein.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease. A proton MR spectroscopic imaging and MRI study.

Hippocampal atrophy detected by MRI is a prominent feature of early Alzheimer's disease (AD), but it is likely that MRI underestimates the degree of hippocampal neuron loss, because reactive gliosis attenuates atrophy. We tested the hypothesis that hippocampal N-acetyl aspartate (NAA: a neuronal marker) and volume used together provide greater discrimination between AD and normal elderly than does either measure alone. We used proton MR spectroscopic imaging (1H MRSI) and tissue segmented and volumetric MR images to measure atrophy-corrected hippocampal NAA and volumes in 12 AD patients (mild to moderate severity) and 17 control subjects of comparable age. In AD, atrophy-corrected NAA from the hippocampal region was reduced by 15.5% on the right and 16.2% on the left (both p < 0.003), and hippocampal volumes were smaller by 20.1% (p < 0.003) on the right and 21.8% (p < 0.001) on the left when compared with control subjects. The NAA reductions and volume losses made independent contributions to the discrimination of AD patients from control subjects. When used separately, neither hippocampal NAA nor volume achieved to classify correctly AD patients better than 80%. When used together, however, the two measures correctly classified 90% of AD patients and 94% of control subjects. In conclusion, hippocampal NAA measured by 1H MRSI combined with quantitative measurements of hippocampal atrophy by MRI may improve diagnosis of AD.

Aged↗

[Minimally differentiated hypoplastic leukemia in two elderly patients].

Patient 1; A 78-year-old woman was admitted to our hospital because of general malaise. Her peripheral blood count showed bicytopenia of 900/microliter with 2% blasts, 7.0 g/dl hemoglobin, and 199,000/microliter platelets. Examination of bone marrow revealed hypocellular marrow with peroxidase-negative blasts (89%). Surface marker analysis of blast cells revealed CD13 agents. Electron-microscopically, myeloperoxidase staining was positive. The diagnosis was hypoplastic leukemia in which blasts had a feature of minimally differentiated acute myeloid leukemia (AML-MO). Patient 2; A 78-year-old man was admitted to our emergency unit because of dizziness and dyspnea on exertion. Examination of peripheral blood showed pancytopenia but no blast cells. Examination of bone marrow showed a markedly hypocellular marrow with 38% blast cells. These blast cells were negative for myeloperoxidase and they had CD13 antigen on their surfaces. The diagnosis was minimally differentiated hypoplastic leukemia. At the time of this writing these two patients had been receiving only red cell transfusions for about six months, and the disease had not progressed.

Aged↗

[Clinical and laboratory findings associated with the severity of community-acquired pneumonia].

To clarify the clinical features of severe community-acquired pneumonia, we retrospectively studied 121 patients treated at our hospital. We divided the patients into three groups, based on the severity, of their disease. Patients were put in the "mild" group (n = 56) if they recovered after treatment with antimicrobial agents only, they were put in the "moderate" group (n = 34) if the required oxygen therapy and recovered, and they were put in the "severe" group (n = 31) if they required mechanical ventilation. Age and underlying disease were recorded, as well as signs, symptoms, and laboratory data obtained during the first 24 hours after admission. The data indicated that the following nine findings were associated with the severity of disease: age of at least 65 years, an underlying disease of (31) the respiratory or central nervous system, dyspnea, a pulse rate of at least 90 beats per minute, a respiratory rate of at least 25 breaths per minute, an albumin concentration no greater than 3.5 g/dl, a blood urea nitrogen level of at least 20 mg/dl, a PaO2 no greater than 60 mmHg or an SaO2 no greater than 90%, and a high score on a scale of the extent of roentgenographic evidence of pulmonary infiltrates. Patients in whom these are found be managed carefully.

Adult↗

Identification of a novel binding site to the integrin alphaIIbbeta3 located in the C-terminal heparin-binding domain of human plasma fibronectin.

Fibronectin has been shown to bind to integrin alphaIIbbeta3 in Arg-Gly-Asp (RGD)-dependent and -independent manners. A recent study has indicated that a 29-kDa dispase-digestive fragment from the C-terminal heparin-binding domain of human plasma fibronectin (lacking RGD sequence) inhibits binding of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation (Tanabe, J. , Fujita, H., Iwamatsu, A., Mohri, H., and Ohkubo, T.(1993) J. Biol. Chem. 268, 27143-27147). We provide here the evidence that a peptide corresponding to residues from Ala1704 to Glu1718 (designated F1) from this fragment inhibited binding of 125I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation. The F1 peptide bound directly to alphaIIbbeta3 integrin receptor. These results indicate that a novel binding site in the C-terminal heparin-binding region of fibronectin is localized within the residues from Ala1704 to Glu1718. Binding of 125I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets was not inhibited by RGDS peptide and the 12-residue peptide from the cell-binding domain of fibronectin, suggesting that binding site in the C-terminal heparin-binding domain may be different from those of RGDS and the 12-residue peptide. This additional alphaIIbbeta3-binding domain(s) in fibronectin may also play some role for prevention of thrombus formation by direct interaction with alphaIIbbeta3.

Adenosine Diphosphate↗

[Pneumonia and mortality in patients requiring prolonged mechanical ventilation].

We examined patients who required prolonged (>60 days) mechanical ventilation. A total of 31 patients were studied, 23 with pulmonary disease, 4 with neurologic disease and 4 with other conditions. Many of these patients were elderly. The survival rates one year and two years after the start of mechanical ventilation were 40% and 33%, respectively. Respiratory tract infection was the most common and most serious complication, and ventilator-associated pneumonia was the main cause of death. It is difficult but quite important to prevent these complications, especially ventilator-associated pneumonia.

Adult↗

[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↗

[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↗

[Acute appendicitis caused by mucorales in a patient with severe aplastic anemia: report of an autopsy case].

A male patient with severe aplastic anemia was admitted for bone marrow transplantation. While waiting for a donor, high doses of methylprednisolone, anabolic steroid and granulocyte colony stimulating factor were given without response. Deferoxamine was administered for prophylaxis of hemochromatosis because of high level of ferritin. Acute right lower abdominal pain and pyrexia developed. A diagnosis of acute appendicitis was made and appendectomy was performed. The histopathological examination of the resected appendix revealed necrotizing hemorrhagic appendicitis with numerous hyphae of Mucorales. Though anti-fungal agent (amphotericin B) administration was continued, he subsequently developed ileo-cecal abscess and eventually died due to myoglobinuric nephropathy caused by extensive necrosis of the iliopsoas muscle. Autopsy revealed dissemination of hyphae of Mucorales in lungs, kidneys, large vessels and muscle of the bilateral lower limbs. Systemic vascular invasion and embolization of fungal hyphae were also observed. However, culture of exudate sampled from ileocecum yielded no Mucorales. It was emphasized that antemortem diagnosis and effective anti-fungal treatments are essential for the management of intestinal mucormycosis. The relation ship between mucormyocosis and deferoxamine was also discussed.

Acute Disease↗

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↗

Dexamethasone inhibits the production of macrophage inflammatory protein 2 in the leukocytes in rat allergic inflammation.

In the air pouch-type allergic inflammation model in rats, when the infiltrated leukocytes in the pouch fluid collected 4 h after antigen challenge were incubated, neutrophil chemotactic activity in the conditioned medium increased time-dependently. They produced neutrophil chemotactic factors, viz. leukocyte-derived neutrophil chemotactic factor (LDNCF)-2, a major component, and LDNCF-1, a minor component. When the infiltrated leukocytes were incubated in the presence of dexamethasone, neutrophil chemotactic activity in the conditioned medium decreased in a concentration-dependent manner, and production of LDNCF-2 and LDNCF-1 was inhibited. Because purified LDNCF-2 had been found to be identical with rat macrophage inflammatory protein 2 (MIP-2), effects of dexamethasone on the level of MIP-2 mRNA in the leukocytes were investigated. Using the reverse transcription-polymerase chain reaction technique, it was demonstrated that dexamethasone suppressed the level of MIP-2 mRNA in the leukocytes. These results indicate that dexamethasone inhibits MIP-2 production at the transcription level.

Animals↗

Synthetic peptides demonstrate RGD-independent platelet glycoprotein IIb/IIIa recognition site in cell binding domain of human fibronectin.

Fibronectin binds to platelet membrane glycoprotein (GP) IIb/IIIa in both an Arg-Gly-Asp (RGD)-dependent and -independent manner. The identification of an RGD-independent binding domain(s) that interacts with GPIIb/IIIa may be the key to understand the mechanism of thrombus formation. A recombinant fibronectin fragment containing the residues from Ile1359 to Ser1436 (lacking the RGD sequence) had been shown to bind to GPIIb/IIIa in a divalent cation- and activation-dependent manner. To identify a minimal peptide ligand that participates in the recognition of GPIIb/IIIa, we synthesized peptides extending this region, which consist of 12 amino acid residues in length and overlapping by six amino acids. We obtained evidence that two 12-residue peptide sequences from this region (residues 1371-1382 and 1377-1388) inhibit fibronectin binding to GPIIb/IIIa by interacting directly with this receptor, with IC50s of 95 +/- 16 and 104 +/- 19 microM, respectively. These peptides inhibited the binding of fibrinogen to GPIIb/IIIa, as well as ADP-induced platelet aggregation. These results indicate that an RGD-independent GPIIb/IIIa binding site in the cell binding domain of fibronectin was localized within the residues His1377-Ile1382.

Adenosine Diphosphate↗

Case report: inhalation therapy of paromomycin is effective for respiratory infection and hypoxia by cryptosporidium with AIDS.

A 24-year-old man with AIDS and hemophilia A had intractable diarrhea and fever. Upon examination of stool and of a sigmoidal biopsy specimen, cryptosporidium was revealed. Approximately 2 months after admission, respiratory infection with hypoxia due to cryptosporidium developed. Paromomycin inhalation was effective therapy. To the authors' knowledge, this is the first case of respiratory cryptosporidiosis treated successfully by paromomycin inhalation.

AIDS-Related Opportunistic Infections↗