Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 379 records · Page 21Linked to original sources

PubMed1999

[Disappearance of residual disease confirmed by RT-PCR following induction chemotherapy in two hypoplastic leukemia patients with t(8;21)].

Reverse transcriptase-polymerase chain reaction (RT-PCR) methods often detect the AML1/MTG8 fusion transcript even in acute myelogenous leukemia (AML) patients with t(8;21) who have been in long-term remission. We encountered 2 hypoplastic leukemia patients with t(8;21) who achieved cytogenetic remission with short-term conventional chemotherapy. Patient 1 was a 42-year-old woman. Chromosomal analysis detected t(8;21) (q22;q22) and PCR analysis (35 cycles PCR amplification; detection limit 1 x 10(-5) cells) detected the AML1/MTG8 fusion transcript. Complete remission was obtained with 1 course of chemotherapy consisting of low-dose cytarabine (20 mg x 14 days) and etoposide (50 mg x 14 days). After 2 courses of consolidation chemotherapy consisting of conventional-dose cytarabine and mitoxantrone, the RT-PCR findings were negative for the AML1/MTG8 fusion transcript. Patient 2 was a 67-year-old man. Cytogenetic analysis detected t(8;21) (q22;q22), and was positive for the AML1/MTG8 fusion transcript. After 2 courses of induction chemotherapy comprising low-dose cytarabine (20 mg x 14 days) and etoposide (50 mg x 14 days), and 3 courses of conventional consolidation chemotherapy, RT-PCR analysis confirmed the disappearance of the AML1/MTG8 fusion transcript.

Adult↗

PubMed1999

DX-9065a, an orally active factor Xa inhibitor, does not facilitate haemorrhage induced by tail transection or gastric ulcer at the effective doses in rat thrombosis model.

DX-9065a is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). We evaluated the effects of DX-9065a and warfarin on bleeding time and blood loss in rat tail transection model and on blood loss in hydrochloride (HCl)-induced rat gastrointestinal haemorrhage model. The blood loss was determined by measuring the haemoglobin content in saline immersed with transected tail or hematin chloride content in the gaster after HCl administration. DX-9065a or warfarin was administered orally at 1 h or 15-21 h before the haemorrhagic stimuli, respectively. The dose required for 50% inhibition of thrombus formation (ID50) was 21 mg/kg for DX-9065a and 0.75 mg/kg for warfarin in a copper wire-inserted arteriovenous (AV) shunt model. In contrast to DX-9065a (10 or 30 mg/kg), warfarin (0.75 mg/kg) significantly prolonged the bleeding time. In rat tail transection model, the blood loss for the control group was 102+/-41 microl at 20 min after the transection. While warfarin (0.75 mg/kg) facilitated the blood loss about 5 times as much as the control, DX-9065a (10 or 30 mg/kg) did not. In rat gastrointestinal model, the blood loss for the control group was 15.9+/-5.6 microl at 15 min after HCl administration. In contrast to DX-9065a (10 or 30 mg/kg), warfarin (0.75 mg/kg) increased the blood loss about twice as much as the control. Thus, compared with warfarin, DX-9065a only increased bleeding time or blood loss to a minor extent in the doses tested. These observations suggest that direct inhibition of FXa could be preferable to warfarin in the suppression of thrombosis without haemorrhagic complications.

Administration, Oral↗

PubMed1999

[Monitored anesthesia care for a patient with malignant pheochromocytoma].

Monitored anesthesia care (MAC) is being increasingly used in the 1990s for a wide variety of diagnostic and therapeutic procedures. The primary objective in providing MAC is to ensure patients' comfort and safety, whether in the operating room or in other places. We experienced MAC for a patient with pheochromocytoma. A 63-year-old man with hepatic metastasis of malignant pheochromocytoma, received transcatheter arterial embolization (TAE) in the angiographic room. Hypertension and ventricular arrhythmia occurred during the hepatic arterial embolization. However, we successfully controlled the hemodynamic changes using phentolamine and propranolol under the close monitoring. He showed an uneventful recovery during postoperative period except for mild hypotension on the third day which needed temporary norepinephrine infusion.

Adrenal Gland Neoplasms↗

PubMed1999

[A case of renal cell carcinoma associated with tuberous sclerosis].

Tuberous sclerosis is associated commonly with renal angiomyolipoma. On the other hand, the relation between tuberous sclerosis and renal cell carcinoma is not widely recognized. We report a case of renal cell carcinoma of the right kidney associated with tuberous sclerosis.

Adult↗

PubMed1999

[Three cases of metastatic renal tumor].

Since solitary metastatic renal tumors are not commonly diagnosed before death, the conclusive treatment of the metastatic renal tumor has not been established. We report three cases of metastatic renal tumors and discuss the indication of surgical therapy for metastatic renal tumors. The first case was in a 64-year-old male who underwent esophagectomy for squamous cell carcinoma. Seven months after the operation, a right renal tumor was found. The second case was in a 63-year-old male who underwent right upper pneumonectomy for adenocarcinoma with a right renal tumor, which seemed to be a solitary metastasis. The third case was in a 69-year-old male who underwent right pneumonectomy for adenocarcinoma. One month after the initial operation, a left renal cystic tumor was found. Since, in all cases, the tumors seemed to be solitary metastatic renal tumors without any other metastatic lesions, nephrectomy was performed. Unfortunately, however, the nephrectomy did not improve prognosis and all three patients did within 10 months after the nephrectomy. Nephrectomy may not be recommended in cases of metastatic renal tumors even if no other metastatic lesions can be found by various image examinations.

Adenocarcinoma↗

PubMed1999

[Multiple myeloma presenting as massive ascites].

Ascites is a rare complication of multiple myeloma. We report a case of multiple myeloma with peritoneal involvement. An 80-year-old woman was admitted to our hospital because of massive ascites. Laboratory findings included an Hb of 7.8 g/dl, IgA of 2,160 mg/dl, and CA125 of 942 IU/ml. Immunoelectropheresis analysis detected a monoclonal component of IgA lambda in serum, and of BJP lambda in urine. Bone marrow aspirtion revealed normal cellularity with 32.7% atypical plasma cells. The ascites was characterized by an exudate with numerous atypical plasma cells and elevated IgA and CA125 levels. The IL-6 level was 22 pg/ml and 79 pg/ml in serum and ascites, respectively. A diagnosis of IgA lambda multiple myeloma with peritoneal involvement was made. Chemotherapy consisting of melphalan and prednisolone reduced the serum IgA and CA125 levels markedly, and alleviated the patient's ascites.

Aged↗

PubMed1999

[New operative technique to resect of peripheral bronchogenic carcinoma with chest wall invasion using Kent's retractor].

We report the new operative technique for resection of peripheral bronchogenic carcinoma with chest wall invasion using Kent's retractor and hook suspender. Standard muscle sparing thoracotomy cannot obtain the adequate operative field in the posterior chest wall under the scapula because of sparing the latissimus dorsi muscle. To obtain a sufficient operative field at the operation for en bloc chest wall resection, especially with the area of the posterior chest wall under the scapula, resection of the trapezius muscle, rhomboideus major muscle, and latissimus dorsi muscle has been added to muscle-sparing thoracotomy. Through our new technique using Kent's retractor and hook suspender that has been used in the abdominal surgery, assistant surgeon can be eliminated in favor of hanging up the scapula, which is able to be performed much easier to obtain a good operative field. To use the Kent's retractor and hook suspender, the scapula is lifted upward and cranially. With these procedures, the proximal portion of the first, second and third ribs in the posterior chest wall covering by the scapula is able to resect from vertebrocostal junction with muscle-sparing thoracotomy. We examined the apparatus for a case of the right upper lung carcinoma with invasion to the posterior chest wall. We performed right upper lobectomy with chest wall in the area of the second, third and forth ribs with suspending the scapula by Kent's retractor after muscle-sparing thoracotomy.

Adenocarcinoma↗

PubMed1999

[Non-Hodgkin's lymphoma with Toxoplasma encephalitis].

A 62-year-old man was admitted to our hospital due to fever and systemic lymph-node swelling on June 9, 1998. He was given a diagnosis of non-Hodgkin's lymphoma (diffuse mixed T cell lymphoma) with involvement of mediastinum and para-aortic lymph nodes, pleura, peritoneum, and bone marrow. After diagnosis, combined chemotherapy (CHOP regimen) was started. On day 11, the patient's consciusness level suddenly deteriorated. A brain computed tomographic scan showed no abnormal findings. A cytospin smear of cerebrospinal fluid disclosed tachyzoides (Toxoplasmic bodies), thus yielding a diagnosis of Toxoplasma encephalitis. Oral sulfadoxine pyrimethamine rapidly alleviated the patient's consciousness disturbance. One month later, a cytospin smear and RT-PCR analysis of cerebrospinal fluid detected no tachyzoides. Complete remission of lymphoma was achieved after 2 courses of CHOP therapy. Toxoplasma encephalitis should be considered a potential cause of consciousness disturbance in immunocompromised hosts, such as patients with malignant lymphoma. Cytospin smears of cerebrospinal fluid are a useful tool for the early diagnosis of Toxoplasma encephalitis.

Animals↗

PubMed1999

[Clinical significance of serum soluble interleukin-2 receptor level in patients with non-Hodgkin's lymphoma].

The aim of this study was to assess the clinical significance of serum soluble interleukin-2 receptors (sIL-2R) in non-Hodgkin's lymphoma (NHL). Using a sandwich ELISA method, serum sIL-2R levels were measured in 720 samples from 87 patients with NHL (including 65 untreated patients) and 36 patients with other diseases such as infectious mononucleosis. The mean serum sIL-2R level in NHL was 4,017 U/ml (mean +/- SD, 4017 +/- 6352 U/ml). Patients in clinical stages III/IV (5116 +/- 6629) had significantly higher sIL-2R levels than those in clinical stages I/II (813 +/- 611). Patients with sIL-2R levels exceeding 8,000 U/ml had significantly lower survival rates (2-year survival: 12.3%) than those with sIL-2R levels below 8,000 U/ml (2-year survival: 76.0%) (P < 0.01). Multivariate analysis of variables including age, clinical stage, LDH, CRP, performance status, number of extranodal diseases, and sIL-2R demonstrated that sIL-2R and LDH were significant prognostic indicators of overall survival. The upper limit of the 95% confidence interval for maximum sIL-2R level in follow-up of patients with complete remission was 2,014 U/ml. Although an increased sIL-2R level of around 2,000 U/ml in the remission stage did not necessarily suggest relapse of NHL, it did seem to warrant careful follow-up. The serum sIL-2R level appears to reflect tumor activity and may prove to be a useful prognostic indicator in patients with NHL.

Adolescent↗

PubMed1999

Partial hepatectomy strongly increased the mutagenicity of N-ethyl-N-nitrosourea in MutaMouse liver.

The relationship between cell proliferation and mutagenesis can be investigated in vivo due to the advent of transgenic animal mutation assays. In these assays, slowly proliferating tissues, such as mammary gland and liver, that are exposed to mutagens generally have longer manifestation times for mutations and lower mutant frequencies. This may be because the cells have enough time prior to cell division to repair DNA damage. We carried out this study using the MutaMouse positive selection system to investigate the effect of a high rate of cell proliferation induced by partial hepatectomy (PH) on mutation induction. We used a 2 x 2 experimental design for PH (or no PH) and 50 mg/kg N-ethyl-N-nitrosourea (ENU) (or phosphate buffer), with the chemical injected 16-19 hr after PH. In the non-ENU groups, the mean MF was slightly but not significantly higher in the PH group than in the non-PH group. In the ENU non-PH group, the MF was also slightly but not significantly increased. In the ENU PH group, in contrast, the mean MF was 7 times the mean MF of the group that received either treatment alone. These results strongly support the hypothesis that ENU induced pre-mutational DNA lesions in liver are completely repaired prior to cell division, and PH increases the mutagen-induced MF by reducing the amount of time available for such repair.

Animals↗

PubMed1999

Effects of O (6)-alkylguanine-DNA alkyltransferase deficiency in Escherichia coli as the host for the detection of mutations in lacI transgenic mice.

Transgenic mice are widely used to detect gene mutations in vivo induced by a variety of chemicals. It is known, however, that no mutagenicity of methyl methanesulfonate (MMS) is detected in epididymal sperm in various transgenic mice assays, although MMS induces the dominant lethal and specific locus mutations in male mice. To investigate the issue of whether unrepaired lesions in DNA of mature sperm can be transformed into mutations during replication of the lambda phage in Escherichia coli cells, we developed an E. coli strain YG5152, which is a derivative of strain SCS-8 but is deficient in the genes encoding O (6)-alkylguanine-DNA alkyltransferases. When lambda LIZalpha phages were treated with MMS or N-ethyl-N-nitrosourea (ENU) in vitro and infected to the E. coli strains, the mutant frequencies of lacI were markedly higher in strain YG5152 than in strain SCS-8. When Big Blue(trade mark) mice were treated with MMS (160 mg/kg) or ENU (125 or 250 mg/kg) and the phages rescued from mature sperm were infected to the strains, the mutation frequency (MF) of phages from ENU-treated mice at a dose of 250 mg/kg in strain YG5152 was about two times higher than that in strain SCS-8. However, no increase in the MF was observed in the MMS-treated mice even in strain YG5152. These results suggest that, although strain YG5152 efficiently detects ex vivo mutations caused by mutagenic alkyl adducts formed by MMS in lambda phage DNA, no detectable levels of mutagenic methyl adducts are present in mature sperm of MMS-treated mice. Possible reasons for this lack of mutagenicity of MMS in mature sperm using transgenic mice assays are discussed.

Animals↗

PubMed1999

Second opinion behaviour among Japanese primary care patients.

BACKGROUND: Second opinion behaviour is often observed among Japanese primary care patients. These patients secretly visit university-affiliated hospitals without informing their doctors. Research to elucidate the psychosocial determinants of this behaviour in the Japanese primary care setting is needed. AIM: To describe the sociodemographic characteristics of second opinion patients (SOPs), and to determine the factors related to this behaviour. METHOD: Patients from the general medicine clinic answered our original questionnaire and a 30-item General Health Questionnaire (GHQ-30). A random sample of patients was questioned using the Diagnostic Interview Schedule. SOPs were defined as those patients who had visited another medical facility with the same complaint, and 'doctor-shopping' patients (DSPs) were defined as those patients who had visited two or more medical facilities with the same complaint. RESULTS: There were 420 SOPs among 1033 patients (41.0%). The multivariate analysis showed that residence and GHQ-30 were the significant differences between the SOPs and the first-visit patients (FVP) (P < 0.0005 for both factors). Also, the SOPs were anxious and sought advice from anybody, unlike the FVPs. Compared with the DSPs, they had a short duration of illness and they did not feel a worsening of their symptoms (P = 0.0001 for duration of illness; P = 0.006 for condition of illness). CONCLUSION: Our results showed that the SOPs who lived far from the medical school hospital felt anxiety and went to a university-affiliated hospital on the advice of anybody. Determining the reasons for this behaviour will require empirical studies regarding the nature of the patient's anxiety for illness.

Adolescent↗

PubMed1999

Intraoperative stress experienced by surgeons and assistants.

BACKGROUND AND OBJECTIVE: To determine the intraoperative stress on surgeons and assistants during cataract surgery, 12 surgeons and 3 assisting nurses were assessed based on their level of professional experience. METHODS: Surgeons were classified as inexperienced, intermediate, or experienced. Nurse assistants were classified as inexperienced or experienced. The intraoperative heart rates and urine adrenaline levels of each participant were measured. RESULTS: Inexperienced surgeons and nurse assistants had the highest heart rates at the beginning of surgery, and the rates tended to decrease toward the end of surgery. All values were higher than the other two groups throughout surgery. In surgeons with intermediate experience, the heart rates were not as high as in the inexperienced personnel; however, the heart rates were high throughout the surgery. The heart rate in one intermediate surgeon was markedly increased when a surgery was simultaneously broadcast on closed-circuit television. In experienced surgeons and a nurse assistant, the measurements increased slightly. CONCLUSIONS: The variations in heart rates and urine adrenaline levels showed characteristic patterns based on the experience of the surgical personnel.

Adult↗

PubMed1998

A splice mutation in the human canalicular multispecific organic anion transporter gene causes Dubin-Johnson syndrome.

The human Dubin Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by chronic conjugated hyperbilirubinemia and impaired hepatobiliary transport of non-bile salt organic anions. A highly homologous phenotype exists in the transport deficient (TR-) Wistar rat, which has a defective canalicular multispecific organic anion transporter (cMOAT). This protein mediates adenosine triphosphate-dependent transport of a broad range of endogenous and xenobiotic compounds across the (apical) canalicular membrane of the hepatocyte. The cDNA encoding rat cMOAT has recently been cloned, and this mutation in the TR- rat has been identified. Subsequently the human homologue of rat cMOAT localized in the liver was found to be the cause of DJS. In an individual with DJS, we have identified a single novel nucleotide substitution in the exon-intron junction of the cMOAT gene which generates liver cDNA with a 67bp exon deletion.

Anion Transport Proteins↗

PubMed1998

Mammalian cell mutants resistant to a sphingomyelin-directed cytolysin. Genetic and biochemical evidence for complex formation of the LCB1 protein with the LCB2 protein for serine palmitoyltransferase.

Lysenin, a hemolytic protein derived from the earthworm Eisenia foetida, has a high affinity for sphingomyelin. Chinese hamster ovary (CHO) cells exhibited a high cytolytic sensitivity to lysenin, but treatment with sphingomyelinase rendered the cells resistant to lysenin. Temperature-sensitive CHO mutant cells defective in sphingolipid synthesis were resistant to lysenin, and this lysenin resistance was suppressed by metabolic complementation of sphingolipids. Selection of lysenin-resistant variants from mutagenized CHO cells yielded two types of sphingomyelin-deficient mutants, both of which showed less lysenin binding capability than wild-type cells. One mutant strain was severely defective in sphingomyelin synthesis but not glycosphingolipid synthesis, and another strain (designated LY-B) was incapable of de novo synthesis of any sphingolipid species and had no activity of serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzing the first step of sphingolipid biosynthesis. LY-B cells lacked the LCB1 protein, a component of SPT, and transfection of LY-B cells with the hamster LCB1 cDNA restored both SPT activity and sphingolipid synthesis to the cells. Expression of an affinity peptide-tagged LCB1 protein in LY-B cells caused the endogenous LCB2 protein to adsorb to a tag affinity matrix. In addition, an anti-hamster LCB2 protein antibody co-immunoprecipitated both SPT activity and the wild-type LCB1 protein with the LCB2 protein. Thus, cell surface sphingomyelin is essential for lysenin-induced cytolysis, and lysenin is a useful tool for isolation of sphingomyelin-deficient mutants. Moreover, these results demonstrate that the SPT enzyme comprises both the LCB1 and LCB2 proteins.

Acyltransferases↗

PubMed1998

Distinct roles of oncostatin M and leukemia inhibitory factor in the development of primordial germ cells and sertoli cells in mice.

Leukemia inhibitory factor (LIF) stimulates the growth of primordial germ cells (PGCs) in mouse embryo. However, as neither mice lacking LIF nor mice lacking the LIF receptor show defects in PGC growth, an alternate cytokine for PGC growth has been postulated. We investigated the role of mouse oncostatin M (mOSM), which is structurally and functionally related to LIF, in germ cell development. While LIF enhanced the survival of migratory as well as postmigratory PGCs, mOSM acted only on the postmigratory PGCs. Consistent with its biological activity, mOSM was found to be expressed in developing gonads. In the male, Sertoli cells in neonatal testis express mOSM; however, its expression is downregulated in adult testes. Moreover, mOSM enhanced the proliferation of Sertoli cells derived from neonatal testes in vitro more than human OSM or LIF. In contrast, postnatal ovaries do not express mOSM. These results indicate that mOSM is a stage- and sex-specific autocrine growth factor for Sertoli cells.

Animals↗

PubMed1998

Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros-derived stromal cell lines.

We report here on a novel stromal cell line, AGM-S3, derived from the aorta-gonad-mesonephros (AGM) region of a 10.5 days postcoitum (dpc) mouse embryo. The AGM-S3 cells promoted production of hematopoietic progenitors and day-12 spleen colony-forming cells from Lin-c-Kit+Sca-1(+) murine primitive hematopoietic cells. They also supported for 6 weeks generation of human multipotential progenitors from cord blood CD34(+)CD38(-) primitive hematopoietic cells. Human long-term repopulating hematopoietic stem cells (LTR-HSC) with the potential to reconstitute hematopoiesis in NOD/SCID mice were maintained on AGM-S3 cells for at least 4 weeks. Flow cytometric analysis showed that CD13, vascular cellular adhesion molecule-1, and Sca-1 were expressed on AGM-S3 cells. Because stem cell factor, interleukin-6 (IL-6), and oncostatin M, but not IL-3, IL-11, leukemia- inhibitory factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, thrombopoietin, and Flk2 ligand were detected in reverse transcription-polymerase chain reaction analysis of AGM-S3 cells, the cells seem to express species-cross reactive molecule(s) other than the cytokines examined and which act on primitive hematopoietic progenitor/stem cells. This cell line is expected to elucidate molecular mechanisms regulating early hematopoiesis and pave the way for developing strategies for expansion of human transplantable HSC.

ADP-ribosyl Cyclase↗

PubMed1998

Structure of a cephalosporin synthase.

Penicillins and cephalosporins are among the most widely used therapeutic agents. These antibiotics are produced from fermentation-derived materials as their chemical synthesis is not commercially viable. Unconventional steps in their biosynthesis are catalysed by Fe(II)-dependent oxidases/oxygenases; isopenicillin N synthase (IPNS) creates in one step the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is produced by the oxidative splitting of a co-substrate, 2-oxoglutarate (alpha-ketoglutarate). This route of controlled ferryl formation and reaction is common to many mononuclear ferrous enzymes, which participate in a broader range of reactions than their well-characterized counterparts, the haem enzymes. Here we report the first crystal structure of a 2-oxoacid-dependent oxygenase. High-resolution structures for apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a model based on these structures, we propose a mechanism for ferryl formation.

Cloning, Molecular↗