[An empirical study on the increase of mild alcoholics in Japan].
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Adult↗
Biomedical subjects
T Sakamoto
Publications and source records attributed to T Sakamoto.
[Relationship between ventricular arrhythmias and myocardial fatty acid metabolism in patients with coronary heart disease: evaluation using iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid].
The effect of metabolic abnormalities of myocardial fatty acids on ventricular arrhythmias was evaluated by myocardial imaging with iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in 27 patients with coronary heart disease. The disturbance of myocardial blood flow was also evaluated using thallium-201 (Tl). The patients were divided into 2 groups based on the character of the premature ventricular contractions: Group A: number of contractions > or = 120 per day and/or consecutive contractions (n = 9, mean age 63.7 yr), and Group B, number of contractions < 120 per day and no consecutive contractions (n = 18, mean age 64.2 yr). Left ventricular ejection fraction was measured by left ventriculography, and significant coronary artery stenosis was defined as stenosis of 75% or greater. Cardiac scintigraphy was performed using single photon emission computed tomography with BMIPP at rest in 27 patients and in the early phase (early Tl) and delayed phase of Tl (delayed Tl) in 20 patients. BMIPP and Tl uptakes were scored as 0: absent, 1: moderately reduced, 2: mildly reduced and 3: normal in 7 segments of the left ventricular wall and then the total scores were calculated in each patient. Ejection fraction significantly correlated with the scores of BMIPP, and early and delayed Tl(p < 0.001, respectively), although the ejection fraction in Group A was significantly less than in Group B (51.2 +/- 16.7% vs 68.2 +/- 14.4%, p < 0.02). The BMIPP scores in Group A were significantly less than those in Group B (14.2 +/- 4.3 vs 17.2 +/- 3.1, p < 0.05), but the early and delayed Tl scores in Group A were not significantly different compared with those in Group B. The BMIPP scores showed no significant differences between the patients with and without significant coronary artery stenosis, but the early and delayed Tl scores in the patients with stenosis were significantly less than those in patients without stenosis (early Tl: 19.8 +/- 2.6 vs 16.8 +/- 2.8, p < 0.01; delayed Tl: 19.6 +/- 2.5 vs 16.8 +/- 3.1, p < 0.05). More patients had values of Tl minus BMIPP scores of at least 3 in Group A than in Group B (early Tl-BMIPP > or = 3: 66.7% vs 7.7%, p < 0.01; delayed Tl-BMIPP > or = 3: 50.0% vs 7.7%, p < 0.05). In patients with coronary heart disease, decreased ejection fraction is thought to be a major cause of ventricular arrhythmias, and also associated with abnormal myocardial metabolism and abnormal myocardial blood flow. Furthermore, ventricular arrhythmias were more closely correlated with abnormal metabolism of fatty acids than with disturbance of blood flow in the myocardium, and large mismatching between the 2 images may be related to risky ventricular arrhythmias in coronary heart disease.
Aged↗
[Out-of-hospital cardiac arrest and the Utstein style: utilization of an international standardized format to evaluate surgical outcome].
The Utstein style is the recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest. The Utstein style was, originally developed to analyze out-of-hospital cardiopulmonary arrest due to cardiac etiology. However trauma remains a major cause of out-of-hospital cardiac arrest and it is recommended that it also be reported accurately by the Utstein style. There exist some controversy regarding treatment methods such as military antishock trousers (MAST) or emergency room resuscitative thoracotomy for cardiac arrest due to trauma. MAST is has been shown to be beneficial experimentally in traumatic shock and cardiac arrest, but this has not been confirmed clinically and Mast is used rarely. Emergency room resuscitative thoracotomy is a common treatment for cardiac arrest due to trauma. There have been no survivors among those who experienced trauma-related cardiac arrest and showed no signs of life before transport to a hospital, although the survival rate of cardiac arrest due to penetrating chest injury is relatively high, clinical date should be accumulated following the Utstein style to determine the indications for these treatments.
Cardiopulmonary Resuscitation↗
[The effect of intraoperative mild hypothermia on the development of perioperative cardiac ischemia].
We evaluated the risk of perioperative cardiac ischemia associated with mild hypothermia as adjunct management for neurosurgical procedures. Forty-seven elective neurosurgical patients were randomly assigned to either hypothermic group (H, n = 24) or normothermic one (N, n = 23). Patients in group H were cooled to and maintained at 34.5 degrees C (tympanic membrane temperature) and rewarmed after main neurosurgical manipulation, while those in group N were kept in normothermic state. Cardiac ischemia was diagnosed with Holter electrocardiogram monitored for 24 hours after admission to the operating room. No differences were observed in demographic data including age, gender, weight, height, rate of having cardiac disease, anesthesia methods, and contents of surgery. Temperature was significantly lower in group H than N both at the lowest point (34.6 +/- 0.5 vs 35.9 +/- 0.6, mean +/- SD) and at the conclusion of anesthesia (35.9 +/- 0.9 vs 36.5 +/- 0.5). Electrocardiographic ST segmental depression was observed in 3 (group H) and 5 cases (group N), and postoperative shivering occurred in 3 (group H) and 2 cases (group N), respectively. Those incidences were not statistically significant (chi-square test, P was set at 0.05). We concluded that intraoperative mild hypothermia might not increase the risk of perioperative cardiac ischemia in patients for neurosurgical procedures.
Adult↗
[Alpha 1-antitrypsin deficiency (Siiyama) with pulmonary emphysema].
A 44-year-old man was admitted to the hospital with dyspnea on exertion. Chest radiographs and pulmonary function tests showed evidence of pulmonary emphysema. Serum alpha 1-antitrypsin (alpha 1-AT) could not be detected by nephelometry, immuno-electrophoresis, or iso-electric focusing. However, allele-specific PCR revealed a genotype homozygotic for an alpha 1-AT deficient variant of the Siiyama allele. An elder sister of the proband was also a homozygous carrier of the Siiyama allele. The amino acid sequence for normal alpha 1-AT variants had been substituted by Arg101-Val213-Glu376 in the proband, demonstrating that the alpha 1-antitrypsin-deficient Siiyama variant in this pedigree was derived from M 1 (Val213).
Adult↗
Evaluation of cytoreductive surgery with pelvic and paraaortic lymphadenectomy and intermittent cisplatin-based combination chemotherapy for improvement of long-term survival in ovarian cancer.
The present study was designed in order to assess the therapeutic values of pelvic and paraaortic lymphadenectomy in cytoreductive surgery and intermittent systematic chemotherapy combining cisplatin, doxorubicin, and cyclophosphamide, namely, intermittent PAC for improvement of the long-term prognosis of patients with epithelial ovarian cancer. Intermittent PAC was administered every 3 months over a period of approximately 2 years. One hundred and fifty-five patients with epithelial ovarian cancer were enrolled in the study. The estimated 10-year survival rate of 42 patients with stage I or II ovarian cancer who received pelvic and paraaortic lymphadenectomy and the intermittent PAC was significantly higher than that of 31 patients with the same stages who did not (83.9% vs. 61.1%, p<0.05). Similarly, the estimated 10-year survival rate of 38 patients with stage III or IV ovarian cancer who underwent the above-mentioned treatments was significantly high compared with that of 44 patients in the same advanced stages who did not (60.4% vs. 25.0%, p<0.01). As for pelvic and paraaortic lymphadenectomy, there was no significant difference in the estimated 10-year survival rates between patients with and without retroperitoneal lymph node metastasis. Multivariate analysis revealed that the performance of pelvic and paraaortic lymphadenectomy was the most important factor leading successful clinical remission of the advanced ovarian cancers. Cytoreductive surgery including pelvic and paraaortic lymphadenectomy and to intermittent PAC were thus suggested to be capable of dramatically improving the long-term survival even in advanced epithelial ovarian cancers.
Adult↗
[Home hospice care at a clinic].
For the people who want to stay at home until their last day, the primary doctor and clinic where they were diagnosed will be the most reliable supports. We have been operating a 19 bed clinic since 1996. In these three years, we have established what we call a "combination palliative care system." A team composed of two doctors, 13 nurses, 3 care aids, a social worker, and a counselor provides home care services as well as outpatient and inpatient care. From April, 1998 to March, 1999, 59 patients died of cancer. Among them, 25 patients died at home. Their primary cancers were lung (7), colon (3), pancreatic (2), breast (2), ovarian (2), brain (1), stomach (1), hepatoma (1), neck (1) and others. First of all, sufficient consultation with patients and family makes this care successful. Through this, the patient can choose his style of care. The whole staff is involved in this care in turn, so that all of us become acquainted with each patient. Home care includes: 1) medical and nursing service available 24 hours a day, 2) activation of social resources for the support of the patient user, 3) constructive cooperation with relevant institutions, 4) relieving the patient's physical and mental suffering, 5) aroma therapy, oil massage, hair cuts and music therapy, and 6) support by volunteers. In this way, as a neighborhood clinic, the combination palliative care system is valuable.
Female↗
[Home palliative care of brain tumor patients from our clinic].
This study investigated whether or not home palliative care of brain tumor patients was possible and various ideas for accomplishing this, over the 2 1/2 years since our clinic was opened. There were 22 patients, aged 42-72 years, comprising 7 cases of glioblastoma, 14 cases of metastatic brain tumor, and 1 case of unknown origin. The control of intracranial hypertension and attacks of convulsion was possible with oral medication or suppositories, but not injection. The prognosis of cancer patients which changed home care showed no remarkable changes, and the home care rate was 53%. Malignant brain tumor patients were able to enjoy time with their families at home during the terminal stage, and die with dignity.
Brain Neoplasms↗
In vitro decidualization activity assay of human endometrial stromal cells.
To address the need for a simple and reliable system for evaluating the effects of bioactive substances on decidualization of endometrial stromal cells, we designed and tested an assay for measuring decidualization activity. With our assay, it is easy to examine the effects of various bioactive substances on endometrial stromal decidualization. For example, as shown in this study, it is now clear that neither RANTES nor gonadotropin releasing hormone agonist has any effect on endometrial stromal decidualization. Our simple assay has also made it possible to evaluate individual stromal decidualization activities and the regulation of decidualization.
Biological Assay↗
Rotatory motion of a cemented acetabular component caused by aseptic loosening and dissociation of the polyethylene liner: a case report.
A 63-year-old woman without rheumatoid arthritis who had undergone cemented total hip arthroplasty developed coxalgia 1 year later. Radiography showed a clear zone at the cement-implant interface and rotatory motion of the acetabular component, so revision surgery was performed 4.5 years after the first operation. Aseptic loosening was noted and 7 spacers outside the acetabular component were broken and buried under the cement mantle. We consider that the rotatory motion may be caused by circumferential loosening of the acetabular component stemming from incomplete implant fixation and also dissociation of the ultra-high-molecular weight polyethylene (UHMWPE) liner from the metal base plate.
Acetabulum↗
VEGF-dependent signaling in retinal microvascular endothelial cells.
We examined the effect of vascular endothelial growth factor (VEGF) on intracellular signal transduction pathways using isolated bovine microvascular endothelial cells (BREC). When cell growth was determined by [3H]thymidine incorporation, it was significantly stimulated by VEGF stimulation. In situ hybridization results also demonstrated that c-fos expression was enhanced by the stimulation. Although BREC expressed Flt-1 and Flk-1 as VEGF receptors at similar levels, VEGF stimulation preferentially enhanced the activity of Flt-1 tyrosine kinase. This stimulation initiated an increase in the level of GTP-form Ras and the activation of mitogen activated protein kinase (MAPK). On the other hand, BREC expressed the Janus kinase (Jak) family members Jak1, Jak2, and Tyk2, and the signal transducers and activators of transcription (Stat) family members Stat1, Stat3, and Stat6. These molecules were tyrosine phosphorylated under culture conditions used, and the phosphorylation of Tyk2 and Stat6 was specifically enhanced by VEGF stimulation. These results demonstrate that, in addition to Ras/MAPK pathways, the Flt-1/Tyk2/Stat6 pathway is important in VEGF signaling in BREC. These signal transduction systems may regulate the growth of retinal endothelial cells.
Animals↗
Cellular response in subretinal neovascularization induced by bFGF-impregnated microspheres.
PURPOSE: To determine the sequence of cellular changes associated with a new rabbit model of subretinal neovascularization (SRN) induced by subretinal injection of basic fibroblast growth factor (bFGF)-impregnated microspheres. METHODS: bFGF-impregnated gelatin microspheres, prepared by forming a polyion complex between gelatin and bFGF, were subretinally implanted into rabbit eyes. The eyes were studied by immunochemistry at 3 days to 8 weeks after implantation. Antibodies to CD4, CD8, cytokeratin, CD31, glial fibrillary acidic protein (GFAP), and RAM11 were used. RESULTS: Cytokeratin-positive retinal pigment epithelial (RPE) cells appeared on day 3 and continued to increase in number in the subretinal space throughout the growth of the SRN membrane, becoming the predominant cell type. Macrophages (RAM11-positive) appeared early, but most disappeared within 7 days. GFAP-positive Müller cells were evident early in the retina but migrated into the subretinal space after 7 days; the gliotic adhesion they formed between the retina and the SRN membrane was prominent at 8 weeks. CD31-positive endothelial cells were first evident at 14 days and formed neovascular channels that were still present for up to 8 weeks. CD4- and CD8-positive lymphocytes appeared in the early stages but were few in number. CONCLUSIONS: SRN membranes are primarily composed of RPE cells and vascular endothelial cells. The membrane adheres to the retina by a gliotic band. The cellular components involved in the membrane of this model resemble those found in SRN membranes removed from patients with age-related macular degeneration.
Animals↗
Long-term beneficial effect of late reperfusion for acute anterior myocardial infarction with percutaneous transluminal coronary angioplasty.
BACKGROUND: Although the short-term and long-term beneficial effects of early coronary revascularization by primary PTCA or thrombolytic therapy have been established for acute myocardial infarction, thrombolytic therapy >24 hours after the onset of acute myocardial infarction has not been shown to improve clinical outcome. The purpose of this study was to assess the effect of late revascularization by primary PTCA over a 5-year period. METHODS AND RESULTS: Eighty-three patients with initial Q-wave anterior myocardial infarction >24 hours after onset were randomized into a PTCA group (n=44) and a no-PTCA group (n=39). Long-term follow-up was conducted with regard to end points, which included cardiac death, nonfatal recurrence of myocardial infarction, and development of congestive heart failure. Left ventricular ejection fraction and regional wall motion at 6 months after myocardial infarction were similar in the 2 groups. Left ventricular end-diastolic and end-systolic volume indexes were significantly smaller in the PTCA group than in the no-PTCA group (P<0.0001). With cardiac events as end points, a 5-year Kaplan-Meier event-free survival analysis revealed that the no-PTCA group had a worse prognosis than the PTCA group (P<0.0001). Patency of the infarct-related artery, left ventricular ejection fraction, end-diastolic volume index, and end-systolic volume index were significantly associated with cardiac events by a Cox proportional hazards analysis (hazard ratios 0.120, 0.845, 1.065, and 1.164, respectively). CONCLUSIONS: In initial Q-wave anterior myocardial infarction, we conclude that even with late reperfusion, PTCA had beneficial effects on cardiac events over the 5-year period after myocardial infarction, with the prevention of left ventricular dilation after myocardial infarction being a possible mechanism.
Acute Disease↗
Stable transfection of retinoblastoma gene promotes contact inhibition of cell growth and hepatocyte nuclear factor-1-mediated transcription in human hepatoma cells.
The retinoblastoma (Rb) gene is a key factor involved in cell cycle regulation. In the present study, alterations in cell growth and expression of the alpha-fetoprotein and albumin genes by the stable transfection of the Rb gene were analyzed in HuH-7 human hepatoma cells. Cell growth was almost similar in the Rb gene-transfected and nontransfected cells at the sparse cell density. However, under a confluent condition, contact inhibition of cell growth was stimulated by the Rb gene transfection. By Northern blotting, the levels of the alpha-fetoprotein and albumin mRNA as well as the transcript of hepatocyte nuclear factor-1 (HNF-1), a liver-specific transcriptional factor regulating both genes, were apparently elevated in the Rb gene-transfected cells, compared with the nontransfected cells. These results suggest that the Rb gene transduction promotes contact growth inhibition in conjunction with the enhanced HNF-1-mediated liver-specific gene transcription in human hepatoma cells.
Carcinoma, Hepatocellular↗
Analogs of cyclic nucleotides in rat liver preservation.
BACKGROUND: Cyclic nucleotides mediate intracellular signal transduction of several vasodilators. In addition to its vascular relaxant effects, cAMP is known to protect endothelial cells and to suppress Kupffer cell activation. On the other hand, cGMP potently ameliorates adhesion of leukocytes and platelets. We tested the effects of two analogs of cyclic nucleotides (8bromo cyclic adenosine monophosphate [8br-cAMP] and 8bromo cyclic guanosine monophosphate [8br-cGMP]) in rat liver preservation. METHODS: In experiment 1, either analog (0.1-1.0 mM) alone was added to University of Wisconsin (UW) solution in a survival study. In experiment 2, donors and recipients were also treated with 8br-cAMP or 8br-cGMP, with the following three groups tested: group 1=control; group 2=administration of 8br-cAMP to donors, UW solution, and recipients; group 3=administration of 8br-cGMP to donors, UW solution, and recipients. Experiment 3 tested combined treatments: group 4=administration of 8br-cGMP to donors and UW solution, and cAMP to recipients; group 5=administration of 8br-cAMP to donors and UW solution, and 8br-cGMP to recipients. To elucidate the roles of each nucleotide, two further groups were tested: group 6=administration of 8br-cAMP to donors and UW solution; group 7=administration of 8br-cGMP to recipients. In experiment 4, rats in groups 1, 5, 6, and 7 were killed at several time points after reperfusion, and percent graft blood flow (%BF), number of accumulated neutrophils, plasma levels of tumor necrosis factor-alpha and interleukin-1, and serum alanine aminotransferase levels were examined. RESULTS: In experiments 1 and 2, no significant effect was observed on animal survival. In experiment 3, a significant increase in animal survival was observed only in group 5 (100%, 7/7, P=0.0004 vs. group 1: 16.7%, 2/12). In group 5, no improvement of %BF was observed during the early phase of reperfusion (15 and 30 min) compared with that in group 1. On the other hand, the %BF of group 5 was significantly higher in the later phase (6 hr), consistent with the decrease in accumulation of neutrophils observed then. Production of tumor necrosis factor-alpha and serum alanine aminotransferase levels were also reduced with this treatment. Histologically, the bleeding and segmental necrosis, observed in group 1, were completely prevented in group 5. CONCLUSIONS: We conclude that restoration of grafts with cAMP and administration of cGMP to recipients led to successful transplantation, and that the two analogs acted synergistically in opposing preservation and reperfusion injury without improvement of graft blood flow during the early phase of reperfusion. The effect was due to their regulation of neutrophil activation and sequestration.
8-Bromo Cyclic Adenosine Monophosphate↗
Overproduction and immuno-affinity purification of myelin proteolipid protein (PLP), an inositol hexakisphosphate-binding protein, in a baculovirus expression system.
Myelin proteolipid protein (PLP) is a major integral membrane protein of central nervous system myelin and is considered to play a significant role in myelination. PLP has a four-transmembrane structure, judging from the hydropathy profile. In addition, it has InsP6 binding activity. Here, we have succeeded in producing PLP in large quantities of 3.9 pg/cell (6 mg/L) by using a baculovirus expression system and developing an efficient purification method, maintaining InsP6 binding activity. The recombinant PLP (rPLP) was purified by ion-exchange and immunoaffinity chromatography in a nonorganic solvent. The final yield of purified rPLP was 36%. The Kd and Bmax values for the InsP6-PLP binding were 55 nM and 33 pmol/microgram protein, respectively. The Kd value of purified rPLP is equal to that of mouse brain PLP. These results indicate that purified rPLP keeps its native conformation and binds InsP6 in an almost one-to-one ratio.
Aged↗
Molecular cloning and characterization of Ca2+-dependent inducible nitric oxide synthase from guinea-pig lung.
We have isolated a full-length cDNA for an inducible nitric oxide synthase (iNOS) from guinea-pig lung. The cDNA has a 3447 bp open reading frame encoding 1149 amino acid residues. The deduced amino acid sequence is approx. 80% identical with iNOS of human epithelial cells and murine macrophages. Consensus recognition sites for cofactors are highly conserved. COS cell lysate transfected with the guinea-pig iNOS shows significant levels of nitric oxide synthase (NOS) activity, and this is inhibited by 79% by chelation of Ca2+ ions. The NOS activity is restored in a concentration-dependent manner by increasing the free Ca2+ level. The NOS activity is also inhibited by trifluoperazine, a calmodulin antagonist, which suggests that the Ca2+ dependence is due to Ca2+-dependent calmodulin binding to the enzyme. Northern blot analysis reveals that the cloned iNOS mRNA is expressed in the lung and the colon in normal guinea pigs. Stimulation in vivo by lipopolysaccharide induces the expression of iNOS in the kidney, the spleen and the colon, but in the lung the same stimulation decreases its expression. These results suggest that the cloned guinea-pig iNOS is distinct in characteristics and expression from previously described iNOS forms.
Amino Acid Sequence↗
Induction of plasminogen activator inhibitor type 1 and type 1 collagen expression in rat cardiac microvascular endothelial cells by interleukin-1 and its dependence on oxygen-centered free radicals.
BACKGROUND: Ischemia with or without reperfusion induces the release of diverse products from monocytes, including cytokines such as interleukin-1 (IL-1). To determine whether these phenomena modulate fibrinolysis and potentially exacerbate impairment of the macrocirculation, microcirculation, or both, we characterized the effects of IL-1 on the expression of fibrinolytic system and matrix proteins in rat cardiac microvascular endothelial cells (CMECs). METHODS AND RESULTS: Confluent CMECs were exposed to IL-1 in serum-free medium for 24 hours, and cell-conditioned medium was assayed for plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of plasminogen activators, and for type 1 collagen with Western blotting. IL-1 (2 ng/mL) specifically increased the accumulation of PAI-1 (4.4 +/- 0.6-fold; mean +/- SD; n = 9) without affecting tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) levels, which remained unchanged. IL-1 increased the accumulation of collagen in conditioned media by 3.5 +/- 0.7-fold (n = 6). Conversely, the accumulation of both PAI-1 and collagen induced by IL-1 was inhibited with an IL-1 receptor antagonist (200 ng/mL; n = 6) and with cycloheximide (10 micrograms/mL; n = 6), implying that protein synthesis was a requirement for the effect. To determine whether the IL-1 effect was mediated by induction of oxygen-centered free radical production, known to be induced by IL-1, we exposed the cells to the hydroxyl radical scavenger tetramethylthiourea (10 mmol/L) and observed abolition of the IL-1-induced increase in the expression of PAI-1 and collagen (n = 6). Conversely, superoxides (generated with 10 mU/mL xanthine oxidase plus 0.6 mmol/L hypoxanthine, and 100 mumol/L hydrogen peroxide) induced the accumulation of PAI-1 and collagen (n = 6). IL-1 (1 microgram/kg body wt) and lipopolysaccharide (50 micrograms/kg body wt) administered in vivo increased PAI-1 protein in rat hearts as detected with Western blotting and PAI-1 immunostaining of rat heart microvessels, indicating the effects delineated in vitro were paralleled by effects in vivo. CONCLUSIONS: These results indicate that IL-1-induced oxygen-centered free radicals stimulate elaboration of PAI-1 and collagen by CMECs. Accordingly, microvascularly mediated inhibition of fibrinolysis may predispose to the persistence of microvascular thrombi, thereby contributing to impaired microcirculatory function, the no-reflow phenomenon, and cardiac dysfunction after ischemia and reperfusion.
Animals↗