PubMed Health⌕ Search

Biomedical subjects

M Hanada

Publications and source records attributed to M Hanada.

At least 55 records · Page 3Linked to original sources
PubMed1997

Conditioning with cyclophosphamide/antithymocyte globulin for allogeneic bone marrow transplantation from HLA-matched siblings in children with severe aplastic anemia.

Graft rejection has been a problem after bone marrow transplantation for patients with severe aplastic anemia (SAA). Ten children with SAA were conditioned for bone marrow transplantation from HLA-identical siblings, using cyclophosphamide (CY, 50 mg/kg) plus antithymocyte globulin (ATG, 15 mg/kg) for 4 successive days. Marrow was infused 36 h after the last dose of CY. Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. All patients achieved durable engraftment at follow-up of 7-41+ months (mean, 25) without significant GVHD. Since investigators have used different sources, doses, and time schedules of ATG, we compared our results with other published reports. We conclude that CY/ATG conditioning is well tolerated and effective in children with SAA.

Adolescent↗
PubMed1997

[A case of olfactory neuroblastoma with intracranial, intraorbital extension and multiple metastases].

A 51-year-old man presented with headache, vomiting and exophthalmus. Neurological examination revealed anosmia, papilledema, decrease in visual acuity, and disability in ocular movement. MRI showed a huge mass which occupied the whole nasal cavity and compressed the frontal lobe upwards and the eyes laterally. CT revealed an extensive bony destruction of the frontal base and bilateral orbits. The mass was biopsied transnasally, and was histologically diagnosed as olfactory neuroblastoma. It was highly radiosensitive and disappeared with a local irradiation of 40 Gy. Three months later the patient complained of a pain radiating from the neck to the right arm. MRI demonstrated a metastasis at the vertebral body of C5. Local irradiation of 30 Gy was performed. The metastatic lesion was removed, and a bone graft taken from the iliac bone was transplanted via an anterior cervical approach. Three weeks later, however, a hard mass appeared in the right of his neck and was surgically removed. By histological examination, it was also identified as a metastatic neuroblastoma to the cervical lymph node. A week after the removal of the cervical metastatic lesion, the metastasis extended rapidly to the left cervical and the bilateral hilar lymph nodes of the lungs. Chemotherapy was performed with a total doses of 800mg of cyclophosphamide, 1.5mg of vincristine, 40mg of pirarubicin, and 80mg of cisplatin. The lesions disappeared within 7 days. However, the patient died from disseminated intravascular coagulation 10 months after the onset. Olfactory neuroblastoma is usually an intranasal neoplasm, but it rarely extends intracranially and intraorbitally as is shown in our case. Basically, olfactory neuroblastoma is a relatively slow-growing tumor though it has a tendency to develop local recurrences over long periods even after aggressive primary treatment, and accompanied with distant metastases. However, our patient showed a very short survival time. Invasive extension and multiple metastases occurred during a short period, followed by disseminated intravascular coagulation. Combined chemotherapy at the initial treatment may be recommended in such an extensive case.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[A case report of coronary artery bypass grafting (CABG) and graft replacement of the ascending aorta for coronary artery disease associated with dissection of the ascending aorta].

A 64-year-old woman waiting for CABG for triple coronary artery disease admitted to our hospital due to chest oppression. One week after the admission, pericardiotomy was performed and blood in the pericardial effusion was found. Emergent chest CT scan revealed dissection of the ascending aorta (DeBakey II) with occluded false lumen. Because her condition was stable, concomitant operation of graft replacement of the ascending aorta and triple coronary artery bypass grafting were performed 3 months after the medical therapy. Her postoperative course was uneventful and the patient remains asymptomatic.

Aortic Dissection↗
PubMed1997

[A case of quadricuspid aortic valve associated with aortic steno-insufficiency].

A case of quadricuspid aortic valve associated with aortic steno-insufficiency was described. A 60-year-old man who had been shown to be suffering from heart murmur was admitted to our hospital. Both aortogram and echocardiogram showed a significant aortic insufficiency with mild stenosis. The aortic valve revealed 4 cusps consisting of 3 equal cusps and a smaller cusp and it had a poor coaptation and mild calcification at each commissure. The coronary orifices were normally located. Aortic valve replacement was carried out with a 25 mm St. Jude Medical valve. Histological findings showed edematous and fibrous changes. His postoperative clinical course was uneventful. Quadricuspid aortic valve is rare and the literatures were reviewed with 33 reported cases in Japan.

Aortic Valve↗
PubMed1997

[A case with nasopharyngeal carcinoma extending into the cavernous sinus].

Nasopharyngeal carcinoma is seen frequently in South China, but it is rare in Japan as well as in Western countries. We reported a rare case with intracranial extension at the initial presentation. This 25-year-old Japanese female showed left abducens palsy. MRI revealed an intracavernous mass with homogeneous enhancement connected with the lesion around the epipharynx through the parapharyngeal space. The mass enlarged gradually, followed by left trigeminal palsy. An elevation of the titer of serum EBV Ig-G was noted. She was operated on via the subtemporal approach, which revealed an intracavernous tumor, connected with the infratemporal fossa mass via the enlarged foramen ovale. Histological examination of the surgical specimen revealed lymphoepithelioma. Local irradiation of 60Co of 63 Gy was performed on the cavernous and parapharyngeal tumors and they decreased in size remarkably. However, metastasis to the upper right neck lymph node occurred, and it was removed. Additional irradiation of 45 Gy was performed on her neck. Chemotherapy was not able to be carried out due to leucocytopenia. At present, 2 years after onset, no regrowth of the tumor has been seen. At initial presentation, intracranial extension of nasopharyngeal carcinoma is very rare. Remission may be obtained by a combination of surgery and irradiation even in cases with metastasis.

Adult↗
PubMed1997

[Preoperative chemoradiation therapy for advanced rectal cancer].

Preoperative concurrent chemoradiation therapy with 5-fluorouracil and cisplatin was applied for advanced rectal cancer. Eligible criteria were as follows: no previous treatment, 4 more than hemicircular occupation, T3 or more invasion to adjacent organs or lymph node metastasis on CT scan, tumor fixation by digital examination. Eleven patients were enrolled with this regimen consisting of 5-FU; 500mg/day x5/w x4, CDDP; 10mg/day X 5/w x4 and radiation; 2Gy x 5/w x 4. As a toxicity, grade 2 leukopenia in 2 cases, grade 2 GI symptoms in one case and radiation dermatitis was observed in 8 cases. As a local response, there were PR in 10 cases and NC in 1 case. Surgical resection was performed on 8 patients. Histological responses in the resected specimens were grade 2, 5 cases; grade 1b, 1 case; and grade la, 2 cases. Operative radicalities were grade A, 3 cases; grade B, 3 cases; and grade C, 2 cases. Preoperative chemoradiation is one of the effective options in multimodal treatment for advanced rectal cancer.

Adenocarcinoma↗
PubMed1996

A cis-acting element in the BCL-2 gene controls expression through translational mechanisms.

The bcl-2 gene becomes activated in many types of human cancers and contributes to neoplastic cell expansion, as well as to resistance to radiation and chemotherapy, by blocking programmed cell death or apoptosis. The expression of this proto-oncogene is regulated at both the transcriptional and post-transcriptional levels. DNA sequence comparisons of human, mouse, rat and chicken bcl-2 cDNAs revealed the presence of an open reading frame (ORF) [correction of (OFR)] located upstream of the normal coding region. Because upstream ORFs (uORFs) have been associated with translational repression, we analysed the functional significance of the 11 amino-acid uORF in the human BCL-2 gene (-119 to -84 bp). Deletion of this uORF from chloramphenicol acetyltransferase (CAT) reporter gene constructs that contained the bcl-2 promoter and entire 5'-untranslated region (5'-UTR), as well as introduction of an A-->T mutation at position -119 bp that destroyed the AUG-initiation codon, significantly increased CAT activity in HeLa, CEM, and other cell lines, without producing a corresponding elevation in CAT mRNA levels. Positioning this uORF, together with its accompanying Kozak sequences, between a heterologous promoter from SV40 and a CAT reporter gene resulted in marked inhibition of CAT protein production without a decrease in CAT mRNA. Mutation of the start codon (ATG-->TTG) of this uORF completely abolished its inhibitory activity, consistent with a translational mechanism. Taken together, these findings suggest that the uORF located within the 5'UTR of the bcl-2 gene is necessary and sufficient for translational regulation of bcl-2 gene expression.

Animals↗
PubMed1996

SecG plays a critical role in protein translocation in the absence of the proton motive force as well as at low temperature.

SecG is an integral membrane component of E. coli protein translocase. However, a discrepancy exists as to the importance of SecG for protein translocation at 37 degrees C between cells and reconstituted proteoliposomes; protein translocation in deltasecG cells is defective at 20 degrees C but normal at 37 degrees C, indicating that SecG is dispensable at 37 degrees C, whereas SecG remarkably stimulates protein translocation into reconstituted proteoliposomes at 37 degrees C. In this study, protein translocation into membrane vesicles containing or not containing SecG was examined in the presence and absence of the proton motive force at 37 degrees C and 20 degrees C. We found that the absence of the proton motive force renders protein translocation strongly dependent on SecG even at 37 degrees C. Protein translocation into proteoliposomes in the absence of the proton motive force thus required SecG whereas that in cells, which always generate the proton motive force, did not.

Bacterial Outer Membrane Proteins↗
PubMed1996

BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy.

The BCL-2 gene was first discovered because of its involvement in the t(14;18) chromosomal translocations commonly found in lymphomas, which result in deregulation of BCL-2 gene expression and cause inappropriately high levels of Bcl-2 protein production. Expression of the BCL-2 gene can also become altered in human cancers through other mechanisms, including loss of the p53 tumor suppressor which normally functions as a repressor of BCL-2 gene expression in some tissues. Bcl-2 is a blocker of programmed cell death and apoptosis that contributes to neoplastic cell expansion by preventing cell turnover caused by physiological cell death mechanisms, as opposed to accelerating rates of cell division. Overproduction of the Bcl-2 protein also prevents cell death induced by nearly all cytotoxic anticancer drugs and radiation, thus contributing to treatment failures in patients with some types of cancer. Several homologs of Bcl-2 have recently been discovered, some of which function as inhibitors of cell death and others as promoters of apoptosis that oppose the actions of the Bcl-2 protein. Many of these Bcl-2 family proteins can interact through formation of homo- and heterotypic dimers. In addition, several nonhomologous proteins have been identified that bind to Bcl-2 and that can modulate apoptosis. These protein-protein interactions may eventual serve as targets for pharmacologically manipulating the physiological cell death pathway for treatment of cancer and several other diseases.

Apoptosis↗
PubMed1996

Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE.

Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected constrictions of the bile ducts, compatible with primary sclerosing cholangitis (PSC). The symptoms and blood parameters of liver dysfunction were associated with the degree of eosinophilia and high serum IgE levels. During corticosteroid therapy, all of these parameters improved, and morphologic improvements of the bile ducts were also observed. The pathogenesis of PSC may be explained, in part, by the concept of hypereosinophilic syndrome or allergic reaction.

Adult↗
PubMed1996

[A case of isolated congenital mitral insufficiency].

A 1-year and 8-month-old girl admitted to our hospital because of wheeze and dyspnea. Echocardiogram and cardiac catheterization confirmed isolated congenital mitral insufficiency with pulmonary hypertension. She was treated with reconstructive surgery consisting of suture of clefted anterior mitral leaflet and annuloplasty. Her postoperative course was uneventual and mitral regurgitation was remarkably improved.

Female↗
PubMed1996

[The problem of 19 mm St. Jude Medical valve prosthesis in the small aortic annuls--19 mm St. Jude Medical valve vs 23 mm St. Jude Medical valve].

We compared the results of 19 mm SJM aortic valve replacements with those of 23 mm SJM aortic valve replacements conducted the same period. [Material & Method] The subjects were 21 patients who underwent valve replacement with a 19 mm SJM prosthesis (the SJM19A group). The age ranged among 16 and 65-year-old, mean of 51. The body surface area was 1.24 to 1.76 m2, mean of 1.48 m2. The post-operative follow-up period was 156 months at maximum and 44 months on average. We compared the SJM19A group with the SJM23A group by chest X-ray and echocardiography. [Results] Two patients in the SJM19A group died soon after surgery. Of the other patient, 19 were categorized NYHA I and one in NYHA II classification in their late phase. Arrhythmia of Lown IVa developed in one patient. The cardio-thoracic ratio decreased from preoperative 60% in the late phase after surgery (p < 0.002) in the SJM19A group, although there was no significant difference with that in the SJM23A group. Echocardiographic improvement in left ventricular hypertrophy was considerable between before and late after surgery in the SJM19A group, while it was not significantly different between the SJM19A and SJM23A group. The mean value of aorta-left ventricle pressure difference in the late stage was 32 mmHg in the SJM19A group and significantly different from the value in the SJM23A group (p < 0.001). This pressure difference tended to be greater as the follow-up period was progressed, while the percentage decrease in the myocardial mass of the left ventricle tended to decreased with longer follow-up period. This data suggests that an increasing level of aorta-left ventricle pressure difference should raise little problem in the mid-term late stage after surgery but possibly cause a serious problem in the long term. Clinical observation should be continued over a long period of time after surgery.

Adolescent↗
PubMed1996

Recurrent cold hemagglutinin disease following allogeneic bone marrow transplantation successfully treated with plasmapheresis, corticosteroid and cyclophosphamide.

A 10-year-old male with severe aplastic anemia following allogeneic BMT developed a hemolytic crisis on post-BMT day 67. The diagnosis of cold hemagglutinin disease was made based on the findings of anemia, reticulocytosis, positive direct Coombs test, and markedly elevated cold agglutinins. Anti-nuclear antibody and anti-DNA antibody were also increased. Plasmapheresis was effective as an emergency measure. Corticosteroid after plasmapheresis had a transient effect. At the second episode of hemolysis 6 months after BMT, immunosuppressive therapy with cyclophosphamide plus corticosteroid was successfully administered without negative effect on engraftment.

Anemia, Aplastic↗
PubMed1995

Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax.

The Bcl-2 protein is a suppressor of programmed cell death that homodimerizes with itself and forms heterodimers with a homologous protein Bax, a promoter of cell death. Expression of Bax in Saccharomyces cerevisiae as a membrane-bound fusion protein results in a lethal phenotype that is suppressible by co-expression of Bcl-2. Functional analysis of deletion mutants of human Bcl-2 in yeast demonstrated the presence of at least three conserved domains that are required to suppress Bax-mediated cytotoxicity, termed domains A (amino acids 11-33), B (amino acids 138-154), and C (amino acids 188-196). In vitro binding experiments using GST-Bcl-2 fusion proteins demonstrated that Bcl-2(delta B) and Bcl-2(delta C) deletion mutants had a markedly impaired ability to heterodimerize with Bax but retained the ability to homodimerize with wild-type Bcl-2. In contrast, Bcl-2(delta A) and an NH2-terminal deletion mutant Bcl-2(delta 1-82) retained Bax binding activity in vitro but failed to suppress Bax-mediated cytotoxicity in yeast. Sequences downstream of domain C in the region 197-218 also were shown to be required for Bax-binding in vitro and anti-death function in yeast. Analysis of Bcl-2/Bcl-2 homodimerization using both in vitro binding assays as well as a yeast two-hybrid method provided evidence in support of a head-to-tail model for Bcl-2/Bcl-2 homodimerization and revealed that sequences within the NH2-terminal A domain interact with a structure that requires the presence of both the carboxyl B and C domains in combination. In addition to further delineating structural features within Bcl-2 that are required for homo-dimerization, the findings reported here support the hypothesis that Bcl-2 promotes cell survival by binding directly to Bax but suggest that ability to bind Bax can be insufficient for anti-cell death function.

Amino Acid Sequence↗
PubMed1995

Vitamin K prodrugs: 2. water-soluble prodrugs of menahydroquinone-4 for systemic site-specific delivery.

PURPOSE: The hydrochloride salts of the N,N-dimethylglycine esters of menahydroquinone-4 (1-mono, 1; 4-mono, 2; and 1,4-bis, 3) were assessed in vivo as prodrug for the systemic site-specific delivery system of menahydroquinone-4 (MKH), the active form of menaquinone-4 (MK-4, vitamin K2(20)). METHODS: The disposition of MK-4 and menaquinone-4 epoxide (MKO) following the intravenous administration of the prodrugs and MK-4 preparation solubilized with surfactant (H-MK-4) were studied in vitamin K cycle inhibited rats. The relative bioavailability of MKH after the administration of the prodrugs was assessed from the area under the plasma concentration of MKO vs. time curve (AUCMKO). The specific delivery of MKH to its active site (liver) and coagulation activity after the administration of selected prodrug 1 were then compared with those of H-MK-4 in warfarin poisoned rats. RESULTS: All compounds showed linear pharmacokinetics, and significant bioavailability of MKH was also observed following the administration of 1 (188%), 2 (87%) and 3 (135%). Prodrug 1 caused the following increases; AUCliver of MKO from 70.7 +/- 5.77 (H-MK-4) to 167 +/- 7.89 nmol.h/g, MRTliver of MKO, from 3.87 +/- 0.307 to 8.57 +/- 0.432 h. The liver accumulation of intrinsic 1 reached a maximum (88% of dose) by 0.25 h. The rapid and liver-selective uptake and liver esterase mediated MKH regeneration characteristics of 1 enhanced the delivery of MKH to its active site and the selective advantage was increased 5.7 fold. The coagulation activity was extended 1.9 fold by 1 administration. CONCLUSIONS: The results indicated that these highly water-soluble and liver-esterase hydrolyzable ester derivatives of MKH are potential candidates for parenteral prodrugs which can thus achieve the systemic site-specific delivery of MKH. Such effective and selective delivery of MKH to its active site can therefore lead to enhanced pharmacological efficacy and can also avoid the toxicity induced by the solubilizing agent used in the H-MK-4 preparation.

Animals↗
PubMed1995

Vitamin K prodrugs: 1. Synthesis of amino acid esters of menahydroquinone-4 and enzymatic reconversion to an active form.

The efficacy and toxicity of vitamin K depends on the pathway and the extent of enzymatic reductive activation to vitamin K hydroquinone, which is an essential cofactor for the synthesis of clotting factors. Parenteral use of vitamin K is impaired by its water insolubility. With the aim to improve delivery problems associated with menahydroquinone-4 (MKH, 2), an active form of menaquinone-4, N,N-dimethylglycine esters of 2 (1-mono, 4-mono, and 1,4-bis) were synthesized and assessed as potential water-soluble prodrugs for parenteral use. The esters can deliver the hydroquinone to its active site without a quinone reductive activation step. The hydrochloride salts of the esters were found to be quite soluble in water. The hydrolysis of the esters in 20% rat liver homogenate 9000 x g supernatant, rat plasma and phosphate buffer, pH 7.4, at 37 degrees C was kinetically studied in the presence and absence of an esterase inhibitor. The hydrolysis was catalyzed by esterases located in the rat liver and rat plasma and quantitatively yielded 2. These results suggest that esterification of 2 with N,N-dimethylglycine is a promising way for obtaining water-soluble prodrug forms of 2. Based on the high susceptibility to liver esterase, the esters are potential prodrugs for achieving the site-specific delivery of 2.

Animals↗