Amplification and overexpression of the PRAD1/Cyclin D1 gene in a multiple myeloma cell line.
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Biomedical subjects
Publications and source records attributed to H Hata.
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The aim of this study was to test the effects of olprinone after coronary artery bypass grafting (CABG). In order to prevent hypotension caused by olprinone, low doses of catecolamines were used concomitantly. Total 22 elective CABG cases were evaluated. In all cases, moderate hypothermia and cardioplegic cardiac arrest were performed. In 10 cases, continuous intravenous 0.1 microg/kg/min of olprinone, 3 microg/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly (Group I). As a control, the same initial doses of catecolamine (DOB and DOA) of Group I were administered in another 12 patients (Group II). When the pump flow of cardiopulmonary bypass (CPB) was decreased to half, these drugs were administered in both groups. Hemodynamics were recorded before CPB, just after the operation and 3, 6, 12, 24, 48, and 72 hours after the operation. Three hours after the operation, both mean aortic pressure (AoP) and pulmonary artery pressures (PAP) of Group I demonstrated significantly lower values than those of Group II. Cardiac index (CI) of Group I showed significantly higher values than that of Group II until 6 hours after surgery. The systemic vascular resistance index (SVRI) of Group I indicated a significantly lower value than that of Group II until 24 hours after the operation. Pulmonary capillary wedge pressure (PCWP) of Group I demonstrated a significantly lower value than that of Group II. There were no significant differences in urine output, oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. Olprinone increased CI and decreased SVRI, and it showed easy weaning from CPB, demonstrating excellent hemodynamics after CABG. These results suggested that this new phosphodiesterase inhibitor may be effective for not only weaning from CPB but also post-cardiotomy cardiogenic shock.
Various surgical techniques have been employed according to the type of the coronary fistula. In this case, preoperative examinations by aortography and MRI revealed a coronary artery fistula which originated from a site just proximal of the RCA, ran through the interatrial septum and drained into the posterior wall of right atrium. The ratio of pulmonary to systemic blood flow (Qp/Qs) was 1. 95. During surgery, we were not able to ligate or divide the fistula on the cardiac surface because the fistulous vessel originated from the posterior aspect of the proximal RCA. After establishing a cardiopulmonary bypass, the opening of the fistula in the right atrium was closed with an autologous pericardium patch, the surface of the interatrial septum was incised and the fistula was identified. The conduit was then divided and closed in the atrial septum. The postoperative course was uneventful. This approach is able to interrupt the fistula safely without interfering with normal coronary flow. Closure of the outlet and division of the fistula itself is a recommendable method to insure interruption of fistulous communication.
We studied the effects of apafant (WEB 2086 BS), a specific and potent platelet activating factor (PAF) receptor antagonist, on the early and late airway responses in conscious and actively sensitized guinea pigs. An increase in airway resistance (Rs) was seen 1 min after the inhaled antigen challenge (early airway response), followed by another increase in Rs which peaked between 4 and 8 h after the provocation (late airway response). Oral administration of apafant as well as theophylline inhibited both early and late airway responses. Ozagrel, an inhibitor of thromboxane A2 synthetase, salbutamol, a beta2-adrenoceptor agonist, and dexamethasone significantly inhibited either the early or the late airway response only. Disodium cromoglycate inhibited neither the early nor the late airway response. The results showed that apafant inhibited both the early and late airway responses in sensitized guinea pigs and its effect was comparable or superior to that of anti-asthmatic drugs used clinically.
Although Bence Jones protein (BJP) is generally accepted to be critically involved in the pathogenic process of kidney impairment in patients with myeloma, patients with BJP do not always have kidney dysfunction. As proteins often undergo glycosylation and alter their molecular nature, it is expected that the heterogeneity in kidney dysfunction can be explained at least partly by the differential affinity to the kidneys of BJP dependent on its glycosylation. Accordingly, we analyzed the structures of carbohydrates of urine BJP biochemically to correlate the structure with kidney function. BJP was obtained from 16 patients with myeloma, 2 patients with light chain amyloidosis, a patient with plasma cell leukemia, and a patient with Waldenstrom's macroglobulinemia. All BJP had five forms of oligosaccharides: three forms of biantennary oligosaccharides and two forms of triantennaries. The three biantennaries correspond to previously reported oligosaccharides on only lambda-type BJP, whereas the triantennaries are novel oligosaccharides found on BJP. Among the five oligosaccharides, the triantennary oligosaccharide Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-6 [Gal(beta)1-GlcNA(beta)1-4(Gal(beta)1-4GlcNAc(beta) 1-2)Man(alpha)1-3]Man(beta)1-4GlcNAc(beta)1-4GlcNAc showed a significant negative correlation with the serum creatinine level (p = 0.015 by Spearman's correlation test, R = 0.744). Thus determination of BJP glycosylation may be useful for the evaluation of kidney impairment in patients with BJP.
In the pharmacological field, the development of drugs effective for dementia is now widely anticipated because of the increase in the elderly population. Dementia has some histological degeneration in the brain, including the hippocampus. Preclinical evaluations of such drugs use animal models with memory impairment, since memory impairment is a major criterion of dementia. We therefore investigated two animal models with hippocampal degeneration. Neonatal administration of monosodium glutamate (MSG) induced specific degeneration of hippocampal pyramidal cells in the CA1 region of Wistar rats in adulthood. In these animals, the correct response rate during the acquisition period of light-dark discrimination learning was significantly lower than that in the control group. No significant changes were noted in the hippocampal concentrations of neurotransmitter substances, including acetylcholine and glutamate. In the second model, similar histological changes were observed at 3 weeks after oral administration of trimethyltin (TMT). These histological changes were accompanied by a reduction in the intrahippocampal concentrations of acetylcholine and glutamate. In the case of light-dark discrimination learning, neither pre- nor post-training administration of TMT affected the correct response rate during both the acquisition and retention test periods. In the case of 8-arm radial maze learning, the increase in correct response rate was significantly suppressed in comparison with that of the control group when TMT was administered at 4 weeks before starting the acquisition trial. This suppression was followed by a lower response rate in the retention test. On the other hand, the correct response rates in retention tests were not affected when TMT was administered after completion of the acquisition trial. These findings indicate that sole degeneration of the hippocampus was able to induce different types of memory impairment, and single evaluation of a drug with one learning paradigm was difficult to justify that a drug is effective for dementia.
Although almost 40% of patients with multiple myeloma respond to initial chemotherapy, myeloma with no response to initial chemotherapy remains a serious problem. To understand the characteristics of drug-refractoriness of myeloma, fresh tumor cells from 13 untreated myeloma patients were fixed and stained with anti-human immunoglobulins and propidium iodide for subsequent flow cytometric analysis of DNA content. More than 10% of myeloma cells were hyperdiploid in eight cases (hyperdiploid + cases) while less than 10% of myeloma cells were hyperdiploid in five cases (hyperdiploid - cases). The proportion of hyperdiploid cells among all myeloma cells was highly correlated with incidence of myeloma cells with morphologically abnormal nuclei such as those with multiple-nuclei or convoluted nuclei (P = 0.001). Among the eight hyperdiploid + cases, two (2/8) showed good response to subsequent chemotherapy while four of five hyperdiploid - cases (4/5) responded well. Cases with poor response had more hyperdiploid myeloma cells (average 25.7% of all myeloma cells) than sensitive cases (average 6.8%), suggesting a contribution of hyperdiploid myeloma cells to primary drug resistance (P = 0.065). The 3 year survival rate of hyperdiploid+cases was 0% while that of the control group was 41.9%. These results suggest that myeloma cells with abnormal nuclear morphology may show hyperdiploidy and poor response to chemotherapy.
BACKGROUND: Coronary constrictive responses to autacoids become augmented 1 week after balloon injury in our swine model. The present study aimed to elucidate the mechanisms of this effect. METHODS: In 12 hypercholesterolaemic miniature pigs, the coronary constrictive response to serotonin was examined angiographically 1 week after injury. After the angiographic study, organ chamber experiments using excised coronary artery were performed to clarify whether functional changes in endothelial cells or in vascular smooth muscle cells contributed to the hyperconstriction. RESULTS: The coronary constrictive response to serotonin in vivo was significantly greater at the previously injured site than at the non-injured site. The degree of the hyperconstriction at the previously injured site exceeded that predicted from a geometric theory. Histological examination demonstrated that the previously injured site was almost covered with regenerated endothelial cells. In vitro studies demonstrated that serotonin caused significantly greater contraction in coronary artery strips, whether with or without endothelium, from the previously injured site than in those from the non-injured site. Endothelium-dependent relaxation in response to serotonin was comparable at the injured and non-injured sites. CONCLUSIONS: These results suggest that the coronary hyperconstriction response to serotonin 1 week after injury results primarily from hyperreactivity of vascular smooth muscle. Whereas any contribution of endothelial dysfunction or the geometric effect may be minimal.
The reaction of 2,3,5-tri-O-benzyl-D-ribose with the lithium salt of an imidazole derivative gave an adduct 17RS. Treatment of 17RS with 1.5N HCl in refluxing tetrahydrofuran gave the beta-4(5)-ribofuranosylimidazole 19 (35%) and the ribosylimidazole 18 (51%). The latter was converted into beta-19 in 86% yield by the Mitsunobu cyclization. This synthetic method produced only the desired beta-anomer. Protection of the imidazole nitrogen of 19 with an ethoxycarbonyl group followed by debenzylation gave 21, which was successively derived to the 5'-amino derivative 1 via the 5'-substituted phthalimide 23, followed by hydrazine degradation in excellent yield. Compound 1 was then converted into the 5'-cyanoguanidine 2 in 79% yield. The 5'-amino derivatives 3-9 lacking a methyl group were efficiently synthesized. Among them, the cyanoguanidine 5 and phenylthiourea 8 exhibited antiulcer activities with half the efficacy of cimetidine. The molecular conformation of 5 was determined by X-ray structure analysis.
A 37-year-old male who was on chronic dialysis regimen for IgA nephropathy developed acute Stanford A type aortic dissection. Replacement of the ascending aorta was performed with the aid of extracorporeal circulation, selective cerebral perfusion, and open distal anastomosis technique. The site of the intimal tear in the ascending aorta was resected and the gelatin-resorcin-formaldehyde (GRF) glue was applied to both stumps. The outside of dissecting aortic wall was reinforced with Teflon-felt strips. Two months after the operation, the patient required an urgent operation due to threatening spindle evolution of a persisting dissection in the descending aorta. Replacement of the total arch and the descending aorta was carried out via the median sternotomy with the left anterior thoracotomy, and a subclavian incision. Continuous veno-venous hemofiltration was initiated immediately after both operations and the water balance was maintained well. The patient was discharged 1 month postoperatively. It was suggested that the inside of the dissected aortic wall should be also reinforced even when the GRF glue was used in patients who have a fragile intimal flap and a wide tear.
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A 42-year-old male was transferred to our institution by his family doctor because of suspected type A aortic dissection with cardiac tamponade. His physical constitution gave the appearance of Marfan's syndrome. Contrast CT revealed DeBaky type 1 aortic dissection. Angiography detected an Annulo-aortic ectasia complicated by an aortic regurgitation (AR) grade IV. He also suffered from a severe funnel chest. We performed simultaneous procedures of aortic root, arch replacement, and sternal elevation. Upon operation, a staged aortic clamp technique was employed to reduce the period of cardiac arrest. In the sternal elevation, the bilateral internal thoracic arteries were preserved. Post operative course was uneventful. We consider it effective to employ the staged aortic clamp technique in a reconstruction of the entire thoracic aorta in the case of poor cardiac function and to preserve the bilateral internal thoracic arteries in sternal elevation in order to prevent infection.
A 68-year-old male with post myocardial infarction left ventricular aneurysm (LVA) complicated by ventricular septal perforation (VSP) was treated surgically. At first, he was admitted with acute myocardial infarction by a physician. Coronary angiography (CAG) revealed a total occlusion of the left anterior descending coronary artery. It was improved to 99% of stenosis by PTCR. Echo cardiography revealed the VSP. However, the patient was approached conservatively because of complications of severe pneuminitis and acute hepatitis. Cardiac catheterization was performed three months after admission. The data on the catheterization are as follows: Left ventricular (LV) wall dyskinesis is presented at segment 1-5. Global ejection fraction (EF) = 26%, Corrected EF = 40%, LVEDP = 36 mmHg, Qp/Qs = 1.8. Elective surgery was then performed with IABP, LVA was resected 90 x 50 mm in size under ventricular fibrillation. VSP, which was 9 mm in size, was closed directly with Teflon felt strips. LV plication was then made with 3.0 polypropylene under cardiac arrest. Reconstruction of the LV was then performed with a double patch, of which a cow pericardium was laid on top of a Gore-Tex patch. Post operative cardiac function was improved remarkably. We consider this procedure excellent because of the avoidance of thrombus and the maintenance of the LV form.
We evaluated three-dimensional transesophageal echocardiographic assessment of the implanted mechanical valves by rotational scanning method. Patients were 7 mitral valve replacement and one aortic valve replacement, 2 mitral and aortic valve replacement. In 2 cases of 7 mitral valve replacement, the prosthetic valve regurgitation was evaluated using by color Doppler echocardiography. In this study, multiplane transesophageal probe was used. It rotated at 2-degree intervals from 0 to 180 degrees and the three-dimensional reconstruction was performed by echo scan workstation system (TOMTEC Inc, Munich, Germany). In mitral valve replacement cases, the valve motion of bileaflet valve (St. Jude Medical valve and ATS valve) were showed very clearly. The struts was easily recognized in the St. Jude Medical valve (SJM valve) cases. In one of SJM valve cases, the pannus formation was revealed, but it did not disturb valve motion. The prosthetic valve regurgitation can be seen accurately. However, aortic valve and ball valve cases cannot be reconstructed because of artifact from prosthetic valve and ultrasonic direction. The prosthetic valve regurgitation, pannus formation which was difficult to be showed in two-dimensional echocardiography and relationship between annulus and sewing cuff can be evaluated by this three-dimensional echocardiography. In this study, this system has some problems, for example real-time evaluation is impossible, aortic valve and ball valve cases cannot be reconstructed. However, we think that this new technology is suitable for evaluating valve thrombus, valve dysfunction and paravalvular leakage. In conclusion, the three-dimensional echo-cardiography demonstrated, reliable and accurate examination, and it can evaluate various complications of prosthetic valve.
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are homeostatic hormones secreted from the human heart which protect both cardiac and the renal function. It is well known that these hormones increase in patients along with increases in the severity of congestive heart failure or acute myocardial infarction. However, as yet there are no reports in the literature on changes of the secreted level of ANP or BNP in surgical patients undergoing cardiopulmonary bypass (CPB). We evaluated the relationship between ANP, BNP, and perioperative cardiac and renal functions in patients with heart failure caused by CPB. We selected 45 patients of elective open heart surgery. We measured plasma level of ANP in all 45 cases, and BNP in 18 cases at preoperation, postoperation, and postoperatively three days after, respectively. At the same time, the cardiac index (CI) was measured. These cases were divided into the following groups. Group A1 (n = 23): cases in which the preoperative ANP was less than 40 pg/ ml. Group A2 (n = 22): cases in which the preoperative ANP was more than 40. Group B1 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as mach as the normal level. Group B2 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as much as the normal level. Group B2 (n = 10): cases in which the preoperative BNP was more than that of 10 times as mach as normal level. We then carried out a comparative study of the perioperative cardiac and renal functions in group A1 and A2, and group B1 and B2, respectively. In the terms of preoperative cardiac and renal function, there were no significant differences between groups A1 and A2, and there were no significant differences in urinary volume during CPB or post operative CI. However, the urinary volume during CPB of group B1 was significantly more than that of B2. Furthermore, the incidence of postoperative CI in group B1. Furthermore, the incidence of postoperative CI in group B1 was significantly higher than in B2. The preoperative and post operative third day BNP level had significant negative correlations with postoperative CI and postoperative third day CI, respectively (r = -0.641, -0.514, p = 0.008, 0.012). The postoperative ANP and BNP levels tend to a mean level roughly similar to one another because of the easing of cardiac stress by surgery and postoperative management. According to these results and several instances in the literature, a preoperative high BNP is considered to suggest a potential perioperative risk for cardiac and renal function. We conclude that determination of the plasma BNP level can be helpful for decisions related to CPB flow and measures taken to enhance cardiac and renal protection during surgery, and therefore is a useful reference for perioperative management.
Angiostrongylus costaricensis eggs were successfully cultured to first stage larvae in a chemically defined medium. The most suitable medium for development was Ham's F-12 among 7 chemically defined media and 10 serum supplemented media examined. The addition of serum to Ham's F-12 did not provide any further benefits for egg development. When the eggs were cultured in this medium under 8% CO2 in air, they developed and formed larvae inside the eggs 5 days later. Thereafter, the eggs began to hatch to first stage larvae. Ten days after cultivation, 34% of the eggs had developed to first stage larvae. When these first stage larvae were infected to the snail intermediate host, Biomphalaria glabrata, they developed to third stage larvae.
A case of CD5-positive diffuse large cell lymphoma in a patient with autoimmune hemolytic anemia (AIHA) is reported. The patient was diagnosed with AIHA in December 1988. Three and a half years later, the patient complained of fever and left sided flank pain. Abnormal lymphocytes appeared in the peripheral blood and were positive for HLA-DR, CD5, CD19, CD20, and surface immunoglobulin (mu, lambda). The pathological diagnosis of the cervical lymphnode was non-Hodgkin lymphoma; diffuse large cell type with a starry sky-like appearance. Although the 8q24 translocation was not detected by karyotypic analysis of the peripheral blood mononuclear cells (PBMNC), Southern blot analysis revealed that the c-myc rearrangements had occurred. This case showed two rearranged bands with Eco RI, Bam HI, or Bgl II digestion, and a germline band with Hin dIII digestion using a second exon fragment of the c-myc gene as a probe. Despite intensive chemotherapy, this patient died 6 months after being diagnosed with malignant lymphoma. We discuss the c-myc rearrangements in this aggressive CD5-positive diffuse large B cell lymphoma.
Mediastinal lymphangioma is rare in adults, and there are few reports of their computed tomographic (CT) findings. We present the CT results in three cases of mediastinal lymphangioma. One showed a well-defined, multilocular, water-density mass enveloping mediastinal structures, without their displacement or compression; one presented as a well-defined, homogeneous, water-density mass in the right paratracheal region; and one was associated with hemorrhage into cysts and a significant increase in size over 5 years. CT is useful for diagnosis and evaluation of the extent or contents of mediastinal lymphangiomas.