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Biomedical subjects

S Asano

Publications and source records attributed to S Asano.

At least 109 records · Page 6Linked to original sources

[A case of Chinese herbs nephropathy in which the progression of renal dysfunction was slowed by steroid therapy].

The patients was a 43-year-old woman whose chief complaints were nausea and heaviness of the heads. There was a history of toxemia of pregnancy. The patient had previously taken Tenshin Tokishigyaku-ka-goshuyu-shokyo-to for two years because of cold sensitivity. Fever, thirst, and loss of appetite developed from approximately 18 months after she started treatment with the Chinese herbal preparation, and she presented at our outpatient clinic 2.5 years later. On initial examination, deterioration of renal function was evident and the serum creatinine level was 3.4 mg/dl. A renal biopsy specimen showed marked interstitial fibrosis without inflammatory cell infiltration, leading to the diagnosis of Chinese herbs nephropathy (CHN). Steroid therapy was started on the 36th hospital day after a sharp rise in the serum creatinine level to 5.1 mg/dl. This resulted in the rapid improvement of renal function and reduction of the serum creatinine to 2.6 mg/dl by 8 weeks after the initiation of treatment. In a study on the use of steroids for patients with progressive moderate renal dysfunction caused by Chinese herbs, Vanherweghem et al. reported that the progression of renal failure was appreciably slowed in patients given steroids when compared with the control group. We were also able to slow the progression of renal dysfunction in our patient by steroid therapy, although the prognosis of CHN is generally considered to be very poor.

Adult↗

[Effect of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell mobilization in healthy volunteers].

The efficacy and safety of high-dose lenograstim on CD34 positive (CD34+) cell mobilization into peripheral blood were investigated in 18 healthy male volunteers. The volunteers were divided into 3 lenograstim dose groups of 6 subjects each. Lenograstim was administered at a dose of 2, 5, or 10 micrograms/kg/day, b.i.d. by subcutaneous injection for a total of 5 days. The median peak number of CD34+ cells/microliter of blood was 16.3, 53.9, and 96.6 in the 2, 5, and 10 micrograms/kg/day groups, respectively. A positive correlation was observed between the peak CD34+ level and dose of lenograstim (P = 0.002). The percentage of volunteers achieving more than 50 CD34+ cells/microliter of blood was significantly higher in the 10 micrograms/kg/day group (83.3%, P = 0.010) than in the 2 micrograms/kg/day group (0%). On the subject of safety, at least 1 adverse drug reaction (ADR) was observed in each of the volunteers, and a total of 12, 33, and 45 ADRs were observed in the 2, 5, and 10 micrograms/kg/day groups, respectively. A dose-dependent increase in the number of ADRs was also observed, including an elevation of LDH (P < 0.001), bone pain (P < 0.001), and fatigue (P = 0.008). However, no volunteers required symptomatic treatment or discontinuation of lenograstim. We concluded that administration of lenograstim at a dose of 10 micrograms/kg/day for 5 days is highly effective for CD34+ cell mobilization into peripheral blood and tolerable in healthy volunteers.

Adult↗

[Efficacy and safety of cefozopran (CZOP) monotherapy and combination therapy with CZOP and amikacin (AMK) for infections accompanying hematological diseases].

We evaluated efficacy and safety of monotherapy with CZOP (1-2 g x 2/day) and combination therapy with CZOP (1-2 g x 2/day) and AMK (200 mg x 2/day) for infections in patients with hematological diseases. Efficacy was evaluated in 71 patients of monotherapy group and 70 patients of combination therapy group. Underlying diseases were mostly leukemia and lymphoma. Infections included sepsis, suspected sepsis, pneumonia and so on. Efficacy in CZOP monotherapy was excellent in 21 patients (31.3%), good in 23 patients (34.3%), fair in 5 patients (7.5%) and the efficacy rate was 65.7%. On the other hand, in combination therapy, each was 14 patients (21.2%), 23 patients (34.8%), 12 patients (18.2%) and the efficacy rate was 56.1%. Side effects such as eruption were noted in 2 patients. Abnormal laboratory findings were noted in 9 patients. All side effects as well as abnormal laboratory findings were minimal. It was concluded that CZOP monotherapy was effective in the treatment of various infections accompanying hematological diseases.

Adolescent↗

Reflex sympathetic dystrophy following transbrachial cardiac catheterization.

We experienced a rare case of complication by reflex sympathetic dystrophy (RSD) following transbrachial cardiac catheterization which may have been caused by poorly executed hemostasis using a hemostatic device. The symptoms of RSD markedly limited the patientOs daily work activities. Although the transbrachial approach is a useful procedure for cardiac catheterization, interventionalists should be aware that RSD may cause serious complications.

Aged↗

Refractory facial cellulitis following cosmetic rhinoplasty after cord-blood stem cell transplantation.

We report a case of a 38-year-old female patient who developed facial cellulitis after cord-blood stem cell transplantation (CBT). The cellulitis was refractory to treatment with antibiotics and antifungal agents. Because facial cellulitis is rare after transplantation, its mechanism could not be determined exactly. On day 40 after CBT, a nurse with expertise in cosmetic surgery attended our rounds and correctly assumed that the patient had received cosmetic rhinoplasty. Although conventional x-rays of the head were normal, a computed tomographic (CT) scan of the brain disclosed the presence of a foreign body over the nasal dorsum. As a result, the patient's symptoms were diagnosed as facial cellulitis associated with foreign material that had been implanted at the time of cosmetic surgery. At a pretransplantation interview, the patient did not mention her history of rhinoplasty. Even after she was shown the head CT scans that revealed the presence of nasal implants, she denied that she had received rhinoplasty before CBT. Unless we realize that patients may have received cosmetic surgery before transplantation, it is difficult to make a diagnosis of infection associated with foreign implants. To our knowledge this is the first report after transplantation of infection associated with cosmetic surgery. Such infections should be included on the list of complications after bone marrow transplantation.

Adult↗

[Long-term follow up of chronic myelogenous leukemia patients treated with natural interferon alpha--multi-institutional cooperative study].

The effects on survival in patients with chronic myelogenous leukemia (CML) treated with natural interferon alpha (Sumiferon) were analyzed. The subjects were 131 patients with CML who underwent treatment with Sumiferon between August 1991 and December 1992. Sumiferon was administered more than 8 weeks, and patients were followed for 5 years. In the end, 101 patients were analyzed after 30 patients were dropped from the study because they had received bone marrow transplantation. Survivals from the start of Sumiferon administration were 63.4% at 3 years, 52.5% at 4 years, and 42.6% at 5 years, respectively. Survivals were compared between the 74 patients who received Sumiferon administration with 1 year of diagnosis, and the 27 patients who received Sumiferon administration after more than 1 year from diagnosis. The 50% survivals were 2,089 days and 868 days, respectively (p = 0.0011). It was concluded that early administration of interferon alpha results in a prolonged survival of CML patients.

Adult↗

Transcription factor Sp3 activates the liver/bone/kidney-type alkaline phosphatase promoter in hematopoietic cells.

The promoter region of the liver/bone/ kidney-type alkaline phosphatase gene was examined to define the cis-acting regulatory sequences and transcription factors responsible for its expression in hematopoietic cells. Transient transfection experiments revealed that regions deleted up to -154 base pairs upstream from the transcription initiation site had significant activities to induce bacterial chloramphenicol acetyltransferase gene. The shortest DNA fragment was found to contain three GC boxes in addition to a TATA box. Electrophoretic mobility shift assay and Southwestern analysis showed that Sp3 could bind to the fragment. Western blot analysis also detected Sp3 protein in eluate from the DNA probe mixed with the nuclear extracts. Through the use of Drosophila Schneider cells that lack the Sp1 family of transcription factors, Sp3 was shown to activate the basal promoter in a dose-dependent manner. When the amount of Sp3 was limited, the most proximal GC box was found to be critical for the basal promoter activity.

Alkaline Phosphatase↗

Surgical repair of acute left ventricular free wall rupture: report of a case.

We present a case of acute (blowout) left ventricular free wall rupture (LVFWR) that occurred on the third day after inferior myocardial infarction. Because electromechanical dissociation developed abruptly and pericardiocentesis was no effective, there was no time for establishing a cardiopulmonary bypass (CPB). Emergency thoracotomy and direct closure were successfully performed at the bed-side. We believe that acute type of LVFWR in which initial symptom is electromechanical dissociation without any preceding symptoms can be rescued by emergency thoracotomy and direct closure of the rupture with no aid of CPB provided that the rupture is a small tear located on the anterior, lateral, or even the inferior wall of the left ventricle, if hemodynamical stability is obtained.

Aged↗

Glycoprotein 130 and c-kit signals synergistically induce thrombopoietin production by hematopoietic cells.

We have reported that simultaneous activation of glycoprotein (gp) 130 and c-kit signals by interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and stem cell factor (SCF) promotes proliferation of human hematopoietic progenitor cells and their differentiation into erythroid, myelocytic, and megakaryocytic cells. We recently found that erythropoietin produced by erythroid progenitors stimulates erythropoiesis via gp130 and c-kit signals. Here we examined thrombopoietin (TPO) production by hematopoietic cells cultured with IL-6, sIL-6R, and SCF. Reverse transcription-polymerase chain reaction analysis indicated that hematopoietic cells generated from cord blood CD34+ cells with the 3 factors expressed a minor splice variant of TPO messenger RNA, P1 delta E2, which can be translated to TPO protein more efficiently than regularly spliced isoforms. The reduction in c-mpl, receptors for TPO, by antisense oligodeoxynucleotides suppressed the generation of erythroid, myelocytic, and pluripotent progenitors in suspension culture, plus colony formation of megakaryocytic progenitors in addition to these progenitors in clonal culture of cord blood CD34+ cells with IL-6, sIL-6R, and SCF. The addition of anti-human TPO antibody to the clonal culture also suppressed colony formation. These findings indicate that TPO production by hematopoietic cells stimulated by IL-6, sIL-6R, and SCF is involved in promoting their own growth.

Antigens, CD↗

[A case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis associated with systemic sclerosis treated by steroid pulse therapy: a case report].

A 57-year-old woman had been diagnosed as systemic sclerosis (SSc) with Raynaud's phenomenon, acrosclerosis and polyarthritis since 1995. She admitted to our hospital in July 1996 because of general fatigue, hemosputa and progressive renal insufficiency. On admission, the blood pressure was normal and laboratory findings showed elevation of the serum creatinin level and a high titer of the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) (> 1000 EU). The renal biopsy revealed crescentic glomerulonephritis. Both renal insufficiency and high titers of MPO-ANCA improved remarkably after methylpredonisolone pulse therapy. This case was suggestive of elucidating the pathogenesis of SSc and MPO-ANCA related glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗

Subcutaneously inoculated cells and implanted pancreatic cancer tissue show different patterns of metastases in Syrian golden hamsters.

CONTEXT: We studied behavior of the subcutaneously implanted pancreatic tumors and the process of metastasis using syngeneic Syrian golden hamsters. DESIGN: HaP-T1, a cell line derived from nitrosamine-induced pancreatic cancer in Syrian golden hamsters was used for this experiment. Thirty-five animals were divided into two groups: subcutaneous cell inoculation and subcutaneous tissue implantation. The tumor tissue was obtained from subcutaneously implanted cancer cells. One month after implantation, the tumors were resected and studied histopathologically. The animals were followed-up weekly by palpation of the peripheral lymph nodes in order to identify local recurrence. After death, necropsy was performed. Liver, lungs and pancreas specimens were taken for histopathogical study and detection of K-ras point mutation using the PCR/RFLP method. RESULTS: The mean survival time in the subcutaneous cell inoculation group was 151+/-17.5 days, and in the subcutaneous tissue implantation group was 137 +/-12.9 days. During the follow-up, 13 subcutaneously cell inoculated hamsters (86.7%) had right axillary lymph node metastasis while subcutaneously tissue implanted hamsters did not show any palpable lymph nodes. After necropsy, 10 of the 20 subcutaneously tissue implanted animals (50%) showed metastases in the lungs at the histopathological level. However, 16 of the 20 subcutaneously tissue implanted animals (80%) showed K-ras point mutation in the lung specimens. The lungs of the animals of the subcutaneous cell inoculation group did not show any metastases. No metastases were found in the liver or the pancreas in either group. CONCLUSION: This study suggests that homologous subcutaneous cell inoculation and subcutaneous tissue implantation models showed completely different patterns of metastasis. These models may aid further research to clarify the mechanisms of metastasis in pancreatic cancer.

Animals↗

Expression of stromal cell-derived factor-1/pre-B cell growth-stimulating factor receptor, CXC chemokine receptor 4, on CD34+ human bone marrow cells is a phenotypic alteration for committed lymphoid progenitors.

We found that the stromal cell-derived factor-1/pre-B cell growth-stimulating factor receptor, CXC chemokine receptor 4 (CXCR4), is expressed on human CD34+ bone marrow (BM) cells. Stringently FACS-sorted CD34+CXCR4+ BM cells completely lack myeloid, erythroid, megakaryocytic, and mixed colony-forming potential (myeloid progenitors), but give rise to B and T lymphoid progenitors, whereas CD34+CXCR4- BM cells can generate colonies formed by myeloid progenitors and can also develop into these lymphoid progenitors. Therefore, expression of CXCR4 on CD34+ BM cells can allow lymphoid progenitors to be discriminated from myeloid progenitors. Because CD34+CXCR4+ cells are differentiated from CD34+CXCR4- cells, multipotential progenitors located in the BM are likely to be negative for CXCR4 expression. CXCR4 seems to be expressed earlier than the IL-7R and terminal deoxynucleotidyl transferase during early lymphohemopoiesis. These results suggest that the expression of CXCR4 on CD34+ BM cells is one of the phenotypic alterations for committed lymphoid progenitors.

Adult↗

Chimeric domain analysis of the compatibility between H(+), K(+)-ATPase and Na(+),K(+)-ATPase beta-subunits for the functional expression of gastric H(+),K(+)-ATPase.

Gastric H(+),K(+)-ATPase consists of alpha-subunit with 10 transmembrane domains and beta-subunit with a single transmembrane domain. We constructed cDNAs encoding chimeric beta-subunits between the gastric H(+),K(+)-ATPase and Na(+),K(+)-ATPase beta-subunits and co-transfected them with the H(+),K(+)-ATPase alpha-subunit cDNA in HEK-293 cells. A chimeric beta-subunit that consists of the cytoplasmic plus transmembrane domains of Na(+),K(+)-ATPase beta-subunit and the ectodomain of H(+),K(+)-ATPase beta-subunit assembled with the H(+),K(+)-ATPase alpha-subunit and expressed the K(+)-ATPase activity. Therefore, the whole cytoplasmic and transmembrane domains of H(+),K(+)-ATPase beta-subunit were replaced by those of Na(+),K(+)-ATPase beta-subunit without losing the enzyme activity. However, most parts of the ectodomain of H(+),K(+)-ATPase beta-subunit were not replaced by the corresponding domains of Na(+), K(+)-ATPase beta-subunit. Interestingly, the extracellular segment between Cys(152) and Cys(178), which contains the second disulfide bond, was exchangeable between H(+),K(+)-ATPase and Na(+), K(+)-ATPase, preserving the K(+)-ATPase activity intact. Furthermore, the K(+)-ATPase activity was preserved when the N-terminal first 4 amino acids ((67)DPYT(70)) in the ectodomain of H(+),K(+)-ATPase beta-subunit were replaced by the corresponding amino acids ((63)SDFE(66)) of Na(+),K(+)-ATPase beta-subunit. The ATPase activity was abolished, however, when 4 amino acids ((76)QLKS(79)) in the ectodomain of H(+),K(+)-ATPase beta-subunit were replaced by the counterpart ((72)RVAP(75)) of Na(+),K(+)-ATPase beta-subunit, indicating that this region is the most N-terminal one that discriminates the H(+),K(+)-ATPase beta-subunit from that of Na(+), K(+)-ATPase.

Amino Acid Sequence↗

Expression of p21(Cip1/Waf1/Sdi1) and p27(Kip1) cyclin-dependent kinase inhibitors during human hematopoiesis.

Expression of p21 and p27 cyclin-dependent kinase inhibitors is associated with induced differentiation and cell-cycle arrest in some hematopoietic cell lines. However, it is not clear how these inhibitors are expressed during normal hematopoiesis. We examined various human hematopoietic colonies derived from cord blood CD34(+) cells, bone marrow, and peripheral blood cells using a quantitative reverse transcription-polymerase chain reaction assay, immunochemistry, and/or Western blot analysis. p21 mRNA was expressed increasingly over time in all of the colonies examined (granulocytes, macrophages, megakaryocytes, and erythroblasts), whereas p27 mRNA levels remained low, except for erythroid bursts. Erythroid bursts expressed both p21 and p27 mRNAs with differentiation but expressed neither protein, whereas both proteins were expressed in megakaryocytes and peripheral blood monocytes. In bone marrow, p21 was immunostained almost exclusively in a subset of megakaryocytes and p27 protein was present in megakaryocytes, plasma cells, and endothelial cells. In megakaryocytes, reciprocal expression of p27 to Ki-67 was evident and an inverse relationship between p21 and Ki-67 positivities was also present, albeit less obvious. These observations suggest that a complex lineage-specific regulation is involved in p21 and p27 expression and that these inhibitors are involved in cell-cycle exit in megakaryocytes.

Adult↗

The common marmoset as a target preclinical primate model for cytokine and gene therapy studies.

Nonhuman primate models are useful to evaluate the safety and efficacy of new therapeutic modalities, including gene therapy, before the inititation of clinical trials in humans. With the aim of establishing safe and effective approaches to therapeutic gene transfer, we have been focusing on a small New World monkey, the common marmoset, as a target preclinical model. This animal is relatively inexpensive and easy to breed in limited space. First, we characterized marmoset blood and bone marrow progenitor cells (BMPCs) and showed that human cytokines were effective to maintain and stimulate in culture. We then examined their susceptibility to transduction by retroviral vectors. In a mixed culture system containing both marmoset stromal cells and retroviral producer cells, the transduction efficiency into BMPCs and peripheral blood progenitor cells (PBPCs) was 12% to 24%. A series of marmosets then underwent transplantation with autologous PBPCs transduced with a retroviral vector carrying the multidrug resistance 1 gene (MDR1) and were followed for the persistence of these cells in vivo. Proviral DNA was detectable by polymerase chain reaction (PCR) in peripheral blood granulocytes and lymphocytes in the recipients of gene transduced progenitors up to 400 days posttransplantation. To examine the function of the MDR1 gene in vivo, recipient maromsets were challenged with docetaxel, an MDR effluxed drug, yet the overall level of gene transfer attained in vivo (<1% in peripheral blood granulocytes) was not sufficient to prevent the neutropenia induced by docetaxel treatment. Using this model, we safely and easily performed a series of in vivo studies in our small animal center. Our results show that this small nonhuman primate, the common marmoset, is a useful model for the evaluation of gene transfer methods targeting hematopoietic stem cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Filamentous phage replication initiator protein gpII forms a covalent complex with the 5' end of the nick it introduced.

Rolling circle type DNA replication is initiated by introduction of a nick in the leading strand of the origin by the initiator protein, which in most cases binds covalently to the 5' end of the nick. In filamentous phage, however, such a covalent complex has not been detected. Using a suitable substrate and short reaction time, we show that filamentous phage initiator gpII forms a covalent complex with nicked DNA, which rapidly dissociates unless gpII is inactivated. A peptide-DNA complex was isolated from trypsin digest of the complex by ion-exchange column chromatography and gel filtration, and its peptide sequence was determined. The result indicated that gpII was linked to DNA by the tyrosine residue at position 197 from the N-terminus. The mutant protein in which this tyrosine was replaced by phenylalanine did not show any detectable activity to complement gene II amber mutant phage in vivo. In vitro, the mutant protein recognized the origin and bent DNA as well as the wild-type does, but failed to introduce a nick and to relax the superhelicity of cognate DNA.

Coliphages↗

A chimeric gastric H+,K+-ATPase inhibitable with both ouabain and SCH 28080.

2-Methyl-8-(phenylmethoxy)imidazo(1,2-a)pyridine-3acetonitrile+ ++ (SCH 28080) is a K+ site inhibitor specific for gastric H+,K+-ATPase and seems to be a counterpart of ouabain for Na+,K+-ATPase from the viewpoint of reaction pattern (i.e. reversible binding, K+ antagonism, and binding on the extracellular side). In this study, we constructed several chimeric molecules between H+,K+-ATPase and Na+,K+-ATPase alpha-subunits by using rabbit H+,K+-ATPase as a parental molecule. We found that the entire extracellular loop 1 segment between the first and second transmembrane segments (M1 and M2) and the luminal half of the M1 transmembrane segment of H+, K+-ATPase alpha-subunit were exchangeable with those of Na+, K+-ATPase, respectively, preserving H+,K+-ATPase activity, and that these segments are not essential for SCH 28080 binding. We found that several amino acid residues, including Glu-822, Thr-825, and Pro-829 in the M6 segment of H+,K+-ATPase alpha-subunit are involved in determining the affinity for this inhibitor. Furthermore, we found that a chimeric H+,K+-ATPase acquired ouabain sensitivity and maintained SCH 28080 sensitivity when the loop 1 segment and Cys-815 in the loop 3 segment of the H+,K+-ATPase alpha-subunit were simultaneously replaced by the corresponding segment and amino acid residue (Thr) of Na+,K+-ATPase, respectively, indicating that the binding sites of ouabain and SCH 28080 are separate. In this H+, K+-ATPase chimera, 12 amino acid residues in M1, M4, and loop 1-4 that have been suggested to be involved in ouabain binding of Na+, K+-ATPase alpha-subunit are present; however, the low ouabain sensitivity indicates the possibility that the sensitivity may be increased by additional amino acid substitutions, which shift the overall structural integrity of this chimeric H+,K+-ATPase toward that of Na+,K+-ATPase.

Amino Acid Sequence↗

Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25).

Chromosome translocations involving band 12p13 are known to be involved in a variety of hematologic malignancies, some of them resulting in rearrangement of the ETV6/TEL gene. Applying the fluorescence in situ hybridization (FISH) method, we found a cryptic translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia (AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A patient-specific cDNA library was screened with ETV6 cDNA, and a novel fusion transcript was identified between the ETV6 and TRKC/NTRK3 gene located on 15q25. TRKC is a receptor tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known to be expressed broadly in neural tissues but not in hematologic cells, so far. ETV6-TRKC chimeric transcript encoded the pointed (PNT) domain of the ETV6 gene that fused to the protein-tyrosine kinase (PTK) domain of the TRKC gene. Two types of fusion transcript were determined, one that included the entire PTK domain of TRKC and the other in which the 3'-terminal 462 bp of TRKC was truncated within the PTK domain. Western blot analysis showed the expression of both chimeric proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK expressed in the leukemic cells may contribute to cellular transformation by abnormally activating TRK signaling pathways. Moreover, this is the first report on truncated neurotrophin receptors associated in leukemia.

Acute Disease↗