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Biomedical subjects

Kiyoshi Hiruma

Publications and source records attributed to Kiyoshi Hiruma.

At least 19 recordsLinked to original sources
PubMed2006

Aseptic meningoencephalitis presenting with bilateral vestibular ataxia: a case report.

Bilateral vestibular dysfunction is a rare condition, of which peripheral disorders are most common, whereas central disorders are extremely rare. A 35-year-old woman developed fever, headache, dizziness, convulsion, and disturbance of consciousness at the same time. MRI findings were normal. Based on the neurological findings and laboratory abnormalities, she was diagnosed as having aseptic meningoencephalitis. Steroid pulse therapy successfully ameliorated her encephalitis sign. However, isolated bilateral vestibular ataxia and dizziness, together with severe decrease of Caloric nystagmus, became apparent and lasted for the following 3 months, without cerebellar/brainstem involvement.

Adult↗
PubMed2006

Developmental expression and hormonal regulation of different isoforms of the transcription factor E75 in the tobacco hornworm Manduca sexta.

E75A and E75B, isoforms of the E75 orphan nuclear receptor, are sequentially up-regulated in the abdominal epidermis of the tobacco hornworm Manduca sexta by 20-hydroxyecdysone (20E) during larval and pupal molts, with E75A also increasing at pupal commitment (Zhou et al., Dev. Biol. 193, 127-138, 1998). We have now cloned E75C and show that little is expressed in the epidermis during larval life with trace amounts seen just before ecdysis. Instead, E75C is found in high amounts during the development of the adult wings as the ecdysteroid titer is rising, and this increase was prevented by juvenile hormone (JH) that prevented adult development. By contrast, E75D is expressed transiently during the larval and pupal molts as the ecdysteroid titer begins to decline and again just before ecdysis, but in the developing adult wings is expressed on the rise of 20E. Removal of the source of JH had little effect on either E75C or E75D mRNA expression during the larval and pupal molts. At the time of pupal commitment, in vitro experiments show that 20E up-regulates E75D and JH prevents this increase. Neither E75A nor E75D mRNA was up-regulated by JH alone. Thus, E75C is primarily involved in adult differentiation whereas E75D has roles both during the molt and pupal commitment.

Animals↗
PubMed2006

A randomized controlled trial to compare once- versus twice-daily filgrastim for mobilization of peripheral blood stem cells from healthy donors.

Although the mobilization of peripheral blood stem cells from normal donors using granulocyte colony-stimulating factor is widely used, the ideal method for the administration of filgrastim has not been determined. Therefore, we compared the efficacy of peripheral blood stem cell mobilization on day 4 of filgrastim between once-daily (group O) and twice-daily (group T) administration of filgrastim at 400 microg/m(2)/d. In all, 38 and 34 donors were randomly assigned to groups O and T, respectively. The number of CD34(+) cells collected on day 4 was not significantly different (1.74 x 10(6) cells/kg in group O and 2.08 x 10(6) cells/kg in group T, P = .37). The incidence and severity of adverse events were similar in the two groups. The baseline white blood cell count was the strongest predictor of poor mobilization. Donor age, sex, and serum concentrations of several cytokines did not significantly affect the CD34(+) cell yield. In conclusion, once-daily administration of filgrastim at 400 microg/m(2)/d appeared to be appropriate for the mobilization of CD34(+) cells in normal donors when apheresis is planned on day 4 of filgrastim. Selection of a donor with a steady-state white blood cell count of 5.0 x 10(9)/L or more may lead to a lower incidence of poor mobilization.

Adolescent↗
PubMed2006

[A case of recurrent gastric cancer with dihydropyrimidine dehydrogenase (DPD) deficiency].

Dihydropyrimidine dehydrogenase (DPD) is a reducing enzyme for fluoropyrimidine which is a widely-used anti-cancer agent, and its deficiency leads to serious toxicities. We report a rare patient with a DPD deficiency. A 39-year-old man was suspected to have a gastric cancer recurrence from the elevation of CEA. Although TS-1 was administered for five days, it was stopped due to the development of grade 2 anorexia and nausea. Although we administered UFT at his request after a one-month drug rest, grade 1 stomatorrhagia besides the former adverse events developed after five days. Therefore he discontinued it and was admitted to our hospital. After 19 days, he died from multiple brain hemorrhage despite the intensive therapies. We considered that the congenital DPD deficiency caused the development of these adverse events because the DPD value was less than 5 pmol/mg/min in mononuclear cells of peripheral blood.

Adult↗
PubMed2005

Characterization of seven genotypes (A to E, G and H) of hepatitis B virus recovered from Japanese patients infected with human immunodeficiency virus type 1.

To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8 +/- 11.4 [mean +/- standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A plus D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HB-JI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan.

Adult↗
PubMed2005

[Plasma protein derivatives].

Plasma protein derivatives produced from human plasma include albumin, blood coagulation factors, immuno globulins, haptoglobin, and c1-inactivator and have been widely used clinically. However, the HIV-tainted blood scandal in which HIV was transmitted to many Japanese patients through blood coagulation factors, must be remembered. The safety of blood products has increased since then in response to that event. Because blood products are provided by volunteer donors, there is a risk of contamination by unknown pathogens and they must be used appropriately. In addition, blood products including plasma derivatives are defined as "special biological products" and regulated by the new Medicine Act. All physicians who prescribe plasma derivatives should understand not only their clinical use but also social expectations and legal regulations.

Biological Products↗
PubMed2004

Differential control of MHR3 promoter activity by isoforms of the ecdysone receptor and inhibitory effects of E75A and MHR3.

MHR3 is an ecdysone-inducible transcription factor whose expression in both Manduca sexta epidermis and the Manduca GV1 cell line is induced by 20-hydroxyecdysone (20E) in vitro. There are four putative ecdysone response elements (EcRE) in the 2.6-kb flanking region of the MHR3 promoter. The most proximal, EcRE1, is necessary for activation of the promoter by 20E in the GV1 cells because the mutation of EcRE1 caused the loss of responsiveness to 20E. Previous studies showed that EcR-B1/USP-1 bound only to EcRE1 and high levels of this complex increased the 20E-induced activation, whereas the presence of high USP-2 prevented this increased activation. When we expressed EcR-A alone or in combination with USP-1 under the control of Autographa californica baculovirus promoter (pIE1hr), the activation of the 2.6-kb promoter by 20E was reduced by about 50%. Moreover, when EcR-A was expressed together with both EcR-B1 and USP-1, it reduced the normal activation caused by EcR-B1 and USP-1 by 50%. Gel mobility shift assays showed no binding of EcR-A/USP-1 to EcRE1. The presence of EcR-A, however, reduced the binding of EcR-B1/USP-1 by about 50%. These findings suggest that EcR-A competes with EcR-B1 for binding of USP-1, leading to a decline in activity of the promoter. In addition, E75A, another ecdysone-induced transcription factor, and MHR3 itself suppressed MHR3 promoter activity by binding to the monomeric response element (MRE2). Therefore, MHR3 can be down-regulated both by itself and by E75A.

Animals↗
PubMed2004

Nonmyeloablative allogeneic stem cell transplantation for patients with unresectable pancreatic cancer.

OBJECTIVES: To clarify whether nonmyeloablative allogeneic stem cell transplantation (NST) can produce the graft versus tumor (GVT) effect in patients with pancreatic cancer. METHODS: A pilot trial of NST was conducted in 5 patients with unresectable pancreatic cancer. Preparative conditioning consisted of administration of 60 mg/kg cyclophosphamide on days 6 and 7 before transplantation, followed by 25 mg fludarabine per square meter of body surface on each of the last 5 days prior to transplantation. Cyclosporine was started 4 days before transplantation. Peripheral blood stem cells from the patients' HLA-identical siblings were transfused into the patients. RESULTS: Complete donor T-cell chimerism in peripheral blood was obtained in 4 patients on day 15 after transplantation. NST resulted in tumor reduction in 2 patients as determined by CT, decreasing levels of tumor markers in 2 patients, pain relief in 2 patients, and a decrease in pleural fluid in 1 patient. Two patients developed acute graft versus host disease (GVHD) of grade II or III and 2 had chronic GVHD involving skin and/or liver. Administration of immunosuppressive drugs for the treatment of GVHD resulted in the elevation of tumor marker levels. CONCLUSION: These findings are the first to suggest that NST induces a GVT effect on pancreatic cancer.

Adult↗
PubMed2004

Positional nystagmus showing neutral points.

We encountered patients who had their static direction-changing positional nystagmus canceled at about 20-30 degrees yaw head rotation from the supine position. This nystagmus was also canceled when the head was rotated 180 degrees from this position. We call these head positions neutral points. At the neutral points, the cupula of the horizontal semicircular canal of the affected ear is positioned vertical to the gravitational plane and no deflection of the cupula occurs. The positional nystagmus observed (except the neutral points) was thought to occur due to a "heavy cupula" or "light cupula", which may be determined by the specific gravity of its endolymph.

Adult↗
PubMed2004

[Malignant mixed tumor].

The term "malignant mixed tumor" is usually synonymous with "carcinoma in pleomorphic adenoma," a secondary carcinoma developing in pre-existing pleomorphic adenoma. However, it sometimes indicates a group of tumors consisting of carcinoma in pleomorphic adenoma, carcinosarcoma (true malignant mixed tumor) and metastasizing benign mixed tumor, the latter 2 being the most infrequent. According to the data of the Japanese committee on TNM classification for salivary gland carcinomas, carcinoma in pleomorphic adenoma accounted for about 10% of all salivary gland carcinomas, both in the parotid and submandibular glands. The main type of carcinomas arising in pleomorphic adenoma were undifferentiated carcinoma, adenocarcinoma and squamous cell carcinoma. Crude 5- and 10-year survival rates were 54.7% and 42.7%, respectively. Invasive carcinomas and carcinomas of high grade malignancy carried worse prognoses. The treatment of choice for carcinoma in pleomorphic adenoma has consisted of en-bloc excision with wide margin. Invasive growth, facial nerve involvement, lymph node metastasis or high-grade malignant tumor are grounds for postoperative radiation therapy. The role of chemotherapy has not yet been well established.

Adenoma, Pleomorphic↗
PubMed2004

[Autologous peripheral blood stem cell transplantation for Japanese multiple myeloma patients: results of a feasibility study].

A feasibility study on high-dose therapy with autologous peripheral blood stem cell transplantation (HDT/PBSCT) was performed in Japanese patients with multiple myeloma (MM). Twenty evaluable patients younger than 65 years old with stage II/III MM were enrolled in this study. Three courses of VAD were used as initial chemotherapy. High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSCH, and 1.2-89.3 (median 23.4) x 106/kg of CD34+ cells were collected. Single (11 patients) or tandem (9 patients) HDT with melphalan (MEL) 200 mg/m2 or MEL 140 mg/m2 plus TBI 10 Gy were performed. The incidence of grade 4 toxicity (COG) was 10% and treatment-related mortality was 5%. Complete response and tumor reduction of more than 75% were obtained in 4 (21%) and 16 (84%) out of 19 patients, respectively. The actuarial 3-year overall survival (OS) and event-free survival (EFS) after PBSCT/HDT were 65.6% and 22.0%, respectively. The median EFS duration was 18 months. These preliminary results indicated that HDT/PBSCT is feasible for Japanese MM patients. A prospective randomized clinical trial will be required to assess the efficacy.

Adult↗
PubMed2004

[Survey on the threshold for platelet transfusions].

We carried out a survey on platelet transfusions performed in nine general hospitals. We evaluated 303 adults who received a total of 24455 units over 1864 platelet transfusions. The underlying diseases were hematologic disorders with chemotherapy (59.7%), hematologic disorders without chemotherapy (15.5%), hematopoietic stem cell transplantation (18.5%), and others (2.0%). The patient platelet count before transfusion (platelet trigger value) was measured in only 77.1%. The platelet trigger value differed greatly between the hospitals, with an average of 2.2 x 10(4)/microl, a minimum of 1.3 x 10(4)/microl, and maximum of 3.2 x 10(4)/microl. Only 55.3% of the platelet transfusions carried out complied with the Platelet Transfusion Guideline published by the Ministry of Health, Labour and Welfare. The hospitals surveyed could be divided into those who gave mainly around 10 units and those who gave over 10 units. The total dose of platelets transfused was more in the hospitals that used mainly 15 or more unit-PCs than in the hospitals that used mainly 10 unit-PCs. These results indicate that platelet transfusion may be greatly reduced by complying with the 2 x 10(4)/microl of platelet transfusion threshold and by selecting less than 10 units of PC per transfusion.

Data Collection↗
PubMed2003

E74 exhibits stage-specific hormonal regulation in the epidermis of the tobacco hornworm, manduca sexta.

The transcription factor E74 is one of the early genes induced by ecdysteroids during metamorphosis of Drosophila melanogaster. Here, we report the cloning and hormonal regulation of E74 from the tobacco hornworm, Manduca sexta (MsE74). MsE74 is 98% identical to that of D. melanogaster within the DNA-binding ETS domain of the protein. The 5'-isoform-specific regions of MsE74A and MsE74B share significantly lower sequence similarity (30-40%). Developmental expression by Northern blot analysis reveals that, during the 5th larval instar, MsE74B expression correlates with pupal commitment on day 3 and is induced to maximal levels within 12h by low levels of 20-hydroxyecdysone (20E) and repressed by physiologically relevant levels of juvenile hormone I (JH I). Immunocytochemical analysis shows that MsE74B appears in the epidermis before the 20E-induced Broad transcription factor that is correlated with pupal commitment (Zhou and Riddiford, 2001). In contrast, MsE74A is expressed late in the larval and the pupal molts when the ecdysteroid titer has declined to low levels and in the adult molt just as the ecdysteroid titer begins to decline. This change in timing during the adult molt appears not to be due to the absence of JH as there was no change during the pupal molt of allatectomized animals. When either 4th or 5th instar larval epidermis was explanted and subjected to hormonal manipulations, MsE74A induction occurred only after exposure to 20E followed by its removal. Thus, MsE74B appears to have a similar role at the onset of metamorphosis in Manduca as it does in Drosophila, whereas MsE74A is regulated differently at pupation in Manduca than at pupariation in Drosophila.

Amino Acid Sequence↗