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Biomedical subjects

H Hata

Publications and source records attributed to H Hata.

At least 73 records · Page 4Linked to original sources

Toxoplasma gondii: difference of invasion into tissue of digestive organs between susceptible and resistant strain and influence of IFN-gamma in mice inoculated with the cysts perorally.

Because it is widely accepted that there is a significant difference in susceptibility to chronic infection by Toxoplasma gondii among inbred mouse strains with different genetic backgrounds, we compared the distribution of the protozoa in digestive organs at early stages of infection between resistant (BALB/c) and susceptible (C57BL/ 6) mice after peroral infection with Fukaya strain cysts. Furthermore, to determine the influence of interferon gamma (IFN-gamma) on the infectivity of the cysts to the digestive tract, homozygous IFN-gamma knockout mice were utilized. Quantitative competitive polymerase chain reaction (QC-PCR) was employed to assess the distribution of T. gondii in different organs at various times after ingestion of cysts. SAG1, a T. gondii-specific gene, was detected in the small intestine and the caecum in wild-type C57BL/6 mice and in the whole digestive tract in IFN-gamma knockout C57BL/6 at 24 hr after infection. No detectable reaction in QC-PCR was observed in BALB/c mice at 24 hr after ingestion of the cysts. Destruction of the IFN-gamma gene showed less effect on the resistance to infection in BALB/c mice, but remarkable augmentation of infectivity of T. gondii to the rectum and peripheral blood was observed in C57BL/6 mice.

Animals↗

Multiple myeloma associated with serum amino acid disturbance and high output cardiac failure.

We experienced a plasma cell leukemia (PCL) patient complicated with high output cardiac failure (HOCF), proved as his elevated cardiac index and pulmonary artery wedge pressure and decreased systemic vascular resistance index in a hemodynamic study. We found no possible causes of HOCF. Interestingly, HOCF was improved as PCL responded to intensive chemotherapy. On the other hand, he showed consciousness disturbance, and had frequent attacks of generalized seizure. His electroencephalogram showed slow waves, and a spike and wave complex. Hyperammonemia and abnormal amino acid distribution were also found. This abnormal serum amino acid distribution, especially elevated glycine level, was different from that seen in chronic liver failure, and he had no hepatic disease. After intensive chemotherapy, the serum ammonia level and glycine level decreased. In this patient, PCL seemed to be responsible for HOCF, hyperammonemia, and abnormal amino acid distribution. We experienced two more cases of multiple myeloma (MM) with HOCF, hyperammonemia, abnormal serum amino acid distribution, and consciousness disturbance of unknown origin. Those two cases showed slow waves in the electroencephalogram. Improvement was seen in their HOCF, hyperammonemia, and abnormal amino acid levels after chemotherapy. The possibility of MM as a cause of HOCF is discussed.

Adult↗

Establishment of a monoclonal antibody to human myeloma cell: relation to chemotherapy and extramedullar infiltration.

Resistance of myeloma cells to melphalan (L-PAM) is a serious problem. To investigate mechanisms of drug resistance, we generated a monoclonal antibody, clone O3, to melphalan-resistant myeloma cells, KHM-11R. Western blot analysis showed that molecular weight of O3 antigen was approximately 90 kDa. Expression of O3 antigen was approximately two times higher in KHM-11R than in parental melphalan sensitive cell line, KHM-11. O3 was preferentially expressed in plasma cell, B-cell, and monocytic cell lines, but not in T-cell lines. Analysis of bone marrow samples from myeloma patients revealed that 13 of 23 samples expressed O3 antigen at various levels, and that O3 antigen expression in patients correlate with preceding chemotherapy, advanced clinical stage and extramedullar invasion of myeloma cells. Furthermore, patients expressing O3 antigen at the time of diagnosis tended to have poor prognosis. The investigation of O3 antigen in myeloma cells will be useful to reveal the pathophysiology of extramedullar invasion and the mechanism of cell killing by melphalan.

Adult↗

Effects of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass.

To estimate the effectiveness of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass (CPB), a clinical study was made, in elective coronary artery bypass grafting (CABG) cases. 24 consecutive patients underwent elective CABG in our institute. In all cases, moderate hypothermia and cardioplegic(St. Thomas solution) cardiac arrest were performed. In 12 cases, continuous intravenous 0.25 microgram/kg/min of milrinone, 3 micrograms/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly as inotropic agents (Group-I). The same initial doses of catecholamine (DOB and DOA) as the Group-I were administered in another 12 patients (Group-II). When the pump flow of CPB decreased to a half, these drugs were administered in both groups. Hemodynamic data were measured before CPB, just after operation, 3, 6, 12, 24, 48, and 72 hours after operation. There were no significant differences in aortic and pulmonary artery pressure between both groups. However, cardiac index (CI) of the Group-I demonstrated significantly (p < 0.01) higher values than that of Group-II until 24 hours after surgery. Systemic vascular resistance index (SVRI) of the Group-I demonstrated significantly (p < 0.01) lower value than that of Group-II from 3 to 12 hours after operation. There were no significant differences in oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. These results suggested that concomitant usage of milrinone and low dose catecholamine increased CI and decreased SVRI, and made weaning from CPB very easy, demonstrating excellent hemodynamics. This high potential phosphodiesterase inhibitor may be suitable for not only weaning from CPB but also post-cardiotomy cardiogenic shock.

Cardiopulmonary Bypass↗

[A case of coronary arterial fistula originating from both coronary artery and draining to the right atrium].

We encountered a case with bilateral fistulas of coronary arteries into the right atrium, a rare cardiac anomaly. The case was a 17-year-old woman, who visited our hospital at the age of 11 because of fever. At that time, the patient was diagnosed as having a left coronary artery-right atrial fistula through cardiac catheterization (CAG). When the patient developed staphylococcus infected endocarditis at the age of 16, a thick fistula of the coronary artery, directly running from the deformed left coronary arterial sinus, a fistula of the left circumflex branch, and also a fistula of the right coronary artery into the right atrium were detected by CAG. The outlets of these fistulas were closed from the inside of the right atrium under artificial cardiopulmonary circulation and cardiac arrest, and each fistula was ligated at the outside of cardiac chambers. At that time, we took particular care that any branch of the sinuatrial node was not injured. Although all fistulas were confirmed to be closed by postoperative CAG, and no evidence of ischemia was detected by myocardial scintigraphy, deformity of the left coronary arterial sinus remained, requiring further follow up.

Adolescent↗

One-stage repair of interrupted aortic arch and aortopulmonary window.

Interrupted aortic arch type A with aortopulmonary window was diagnosed in a 12-day-old neonate. A successful one-stage repair was undertaken through a midline sternotomy without circulatory arrest. The aortopulmonary window was closed through the anterior wall of communication between ascending aorta and main pulmonary artery with a patch. Position of the arterial cannula was changed during the repair, which made it possible to mobilize and expose the aortic arch for the completion of direct anastomosis.

Aorta, Thoracic↗

In vitro excess ammonia production in human myeloma cell lines.

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.

Ammonia↗

Expression of Bcl-2 family of proteins in fresh myeloma cells.

Members of the Bcl-2 family of proteins, Bcl-2, Bcl-X(L), Bcl-Xs and Bax, are considered to play important roles in the regulation of apoptosis and drug resistance. To understand the significance of these proteins in fresh human myeloma cells, expression of Bcl-2 family of proteins was analyzed by Western blotting in 17 cases with multiple myeloma (MM) and three cases with plasma cell leukemia (PCL). Bcl-2 and Bcl-X(L) were found in 12 and nine samples, respectively. All PCL cases showed co-expression of Bcl-2 and Bcl-X(L). Analysis of MM cases showed that Bcl-2 was preferentially expressed in samples from cases with early clinical stage while Bcl-X(L) tended to be expressed in samples from cases at advanced clinical stage. Bcl-X(L) was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correlation between the expression levels of Bcl-2 or Bcl-X(L) and preceding chemotherapy. Expression of Bax was found in only one patient who had pleural effusion caused by invasion of myeloma cells and a high serum LDH level. Survival analysis revealed that there was no statistical significance in expression of Bcl-2 or Bcl-X(L) although Bcl-X(L) tended to be expressed in cases with poor prognosis. These findings indicate that expression of Bcl-2 family of proteins is heterogeneously regulated in fresh myeloma cells. Expression of Bcl-X(L) and Bcl-2 may correlate with extramedullar invasion and early stage of the disease, respectively. Absence of Bax in myeloma cells may contribute to low sensitivity of myeloma cells to anti-cancer agents since Bax is reported to mediate cytotoxicity of some anti-cancer drugs.

Adult↗

Clinical experiences of percutaneous cardiopulmonary support: its effectiveness and limit.

In recent years, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB) and postcardiotomy cardiac support. From April 1990 to March 1997, a percutaneous cardiopulmonary support (PCPS) system was used in 20 patients with an average age of 58 years (13 males and 7 females). They comprised 11 ischemic, 6 valvular, 2 aortic, and 1 congenital heart disease patients. Our PCPS system consists of a centrifugal pump (BioMedicus BP-80), an oxygenator, and a reservoir. The entire blood contacting surface, including that of the thin wall cannulas, is coated by heparin bonded materials. As a result of this new technology, this system can be used for the long term without systemic heparinization. No major critical thrombi were revealed inside the pumps or circuits. Of the 20 patients, 7 (35%) (Group 1) could be weaned from PCPS, and the remaining 13 (Group 2) could not. In Group 1 although 2 patients suffered from renal failure and pneumonia, respectively, both were discharged from our hospital. The long-term survival rate was 35%. In Group 2 cerebral vascular damage was recognized in 3 patients, renal failure in 4, multiple system organ failure in 4, bleeding in 2, arrhythmia in 1, and leg ischemia in 2. Pulse pressure was significantly elevated due to the recovery of the native heart in Group 1, 2 days after support. However, in Group 2, it did not elevate, and the left ventricular ejection fraction was less than 30%, associated with high left atrial pressure. In conclusion, this heparin coated PCPS system was very simple and easy to control. It demonstrated long-term biocompatibility and was very effective in recovering deteriorated cardiac function. Quicker application of this system can play an important role in preventing severe complications and obtaining better clinical results. If long-term support is necessary, a ventricular assist device (VAD), which is more powerful, durable, and biocompatible, has to be applied instead of PCPS.

Acute Kidney Injury↗

Dhh1p, a putative RNA helicase, associates with the general transcription factors Pop2p and Ccr4p from Saccharomyces cerevisiae.

The POP2 (Caf1) protein in Saccharomyces cerevisiae affects a variety of transcriptional processes and is a component of the Ccr4p complex. We have isolated five multicopy suppressor genes of a pop2 deletion mutation: CCR4, DHH1 (a putative RNA helicase), PKC1, STM1, and MPT5 (multicopy suppressor of pop two). Overexpression of either the CCR4 or DHH1 genes effectively suppressed phenotypes associated with pop2 mutant cells; overexpression of PKC1, STM1, or MPT5 genes produced only partial suppression. Disruption of the CCR4 or DHH1 genes resulted in phenotypes similar to those observed for pop2 cells. In addition, overexpression of the DHH1 gene also suppressed the ccr4 mutation, suggesting a close relationship between the POP2, CCR4, and DHH1 genes. Two-hybrid analysis and coimmunoprecipitation experiments revealed that Pop2p and Dhh1p interact physically, and these and other data suggest that Dhh1p is also a component of the Ccr4p complex. Finally, we investigated the genetic interaction between factors associated with POP2 and the PKC1 pathway. The temperature-sensitive growth defect of dhh1 or mpt5 cells was suppressed by overexpression of PKC1, and the defect of mpk1 cells was suppressed by overexpression of MPT5. These results and phenotypic analysis of double mutants from the POP2 and PKC1 pathways suggested that the POP2 and the PKC1 pathways are independent but have some overlapping functions.

Bacterial Proteins↗

Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells.

The role of estrogen and estrogen-related growth factors in the mechanism of hormone dependency of endometrial adenocarcinoma cells was investigated. The proliferation of hormone-responsive human endometrial adenocarcinoma cells (Ishikawa cells), which possess both estrogen and progesterone receptors, was optimally stimulated by 10 nM estradiol. Both transforming growth factor (TGF)-alpha and epidermal growth factor (EGF), added to the culture media, stimulated the proliferation of Ishikawa cells in a dose-dependent manner. Anti-TGF-alpha antibody completely eliminated the stimulatory effects of TGF-alpha. Anti-EGF receptor antibody inhibited the proliferation of these cells. The production of TGF-alpha into culture media was 5-40 pg/10 cells/24 h in 9 human endometrial adenocarcinoma cells. Ten nanomoles of estradiol increased the TGF-alpha production of Ishikawa cells by approximately 2.5-fold of the control level. In contrast, the production of TGF-alpha in hormone-unresponsive HEC-50 cels was not influenced by estradiol. C-erbB-2 oncoprotein expression of human endometrial adenocarcinoma cells, detected by both immunocytochemical staining and Western blot analysis, was associated with the tumor grade of the original tumor tissues. Ten nanomoles of estradiol clearly increased the c-erbB-2 oncoprotein levels at an optimal incubation period of 72 h, whereas estradiol did not affect the expression in HEC-50 cells.

Adenocarcinoma↗

Effects of nucleic acid inhibitors on the development of Angiostrongylus costaricensis in vitro.

Nucleic acid biosynthesis of Angiostrongylus costaricensis was examined with various inhibitors; aminopterin (inhibitor of purine and pyrimidine de novo biosynthetic pathways), 8-azaguanine (specific inhibitor of purine salvage pathway) and PALA (specific inhibitor of pyrimidine de novo biosynthetic pathway) were applied in in vitro culture developing from the third stage larvae to young adult in chemically defined medium. It was suggested that A. costaricensis possessed functional purine and pyrimidine de novo biosynthetic pathways and also that they could utilize exogenous sources of purines and pyrimidines by salvage pathways for their development.

Aminopterin↗

Left atrial myxoma with an atrial septal defect: a case report and review of the literature.

We report a case of a 49 year-old Japanese woman with a left atrial myxoma complicated by an atrial septal defect diagnosed intraoperatively, which was classified as in secundum defect and was 28x110 mm in diameter. The tumor, which was attached by a pedicle to the posterior wall of the left atrium near the posterior commissure of the mitral valve, was removed together with a small portion of the left atrial wall. The postoperative course was uneventful. The pathologic findings were consistent with the diagnosis of myxoma. Since the defect was functionally canceled by the myxoma, the diagnosis of an atrial septal defect was not confirmed preoperatively even by color Doppler echocardiography and cardiac catheterization. Tumor embolization is one of the critical complications of myxoma. Fortunately, she didn't suffer from either systemic or pulmonary emboli. During surgery of myxoma with atrial septal defect, careful manipulation is needed, especially at caval cannulation so as not to damage the tumor directly. In the cases with atrial septal defect or patent foramen ovale, myxomas are generally situated on the interatrial septum. However, in this case the tumor was located on the posterior wall of the left atrium.

Cardiac Catheterization↗

Macroscopic aspects of cloth-covered Starr-Edwards prostheses at reoperation: what the precursory valve teaches us.

BACKGROUND AND AIMS OF THE STUDY: Cloth-covered Starr-Edwards ball valves were the first choice in prosthetic substitution at the authors' institution between June 1968 and March 1977. This study investigated, retrospectively, macroscopic aspects of the prostheses at reoperation. METHODS: Among 59 survivors who underwent isolated aortic or mitral valve replacement, 12 required reoperation for valve dysfunction (five aortic valve replacements, seven mitral valve replacements). Reoperation was necessitated by valvular endocarditis, paravalvular leak, hemolysis, thromboembolism, orifice stenosis attributable to pannus, and inappropriate sizing related to growth and thrombus. The mean time to reoperation was 11.7 +/- 6.2 years after initial surgery (range: 2 years 4 months to 21 years 8 months). RESULTS: Marked cloth wear was observed in all aortic prostheses, but only slight wear in mitral valves. Pannus formation was observed around the orifice in both aortic and mitral prostheses, but strut cloth was not extensively covered by autologous tissue. In mitral valves, strut cloth was only slightly worn and less loose than that of the aortic valve. These changes notably affected prosthetic valve function, the most significant problem in mitral prostheses being thrombus (four of seven valves). CONCLUSIONS: Pannus formation and thrombus caused by the reaction of the patient's tissues remain major problems in the use of artificial valves, and require further work for their improvement.

Adolescent↗