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Biomedical subjects

A Sasaki

Publications and source records attributed to A Sasaki.

At least 91 records · Page 5Linked to original sources
PubMed2001

[Two cases of reoperative coronary bypass grafting through a small left thoracotomy].

A reoperation by a MIDCAB (minimally invasive direct coronary artery bypass) was performed on 2 patients, including one who had undergone a surgical repair of a left ventricular rupture and another who had undergone a coronary artery bypass operation. In both patients, the left internal thoracic artery was isolated by a left small thoracotomy and then was anastomosed to the LAD (left anterior descending artery). One patient showed stenosis at the site of anastomosis and thus required coronary arterioplasty postoperatively, but was discharged without any further complications. When performing a reoperation by MIDCAB, complications such as injuries to the heart and patent graft during surgery and postoperative complications can be minimized by only performing a bypass to LAD. Such a bypass is usually sufficient in cases in which either marked adhesion is expected in the area of the circumflex artery or if anastomosable branches are not available in the area of the circumflex artery. This surgical technique was found to be an effective modality for a reoperation of the coronary artery, if suitable cases are carefully selected.

Aged↗
PubMed2000

Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function.

Dlx5, a member of the Dlx family of homeodomain proteins, plays a critical role in bone development and fracture healing. To understand the molecular mechanism underlying the transcriptional regulation by Dlx5, we performed yeast two-hybrid screening and isolated a novel protein, Dlxin-1, that binds Dlx5 and regulates its transcriptional function. Dlxin-1 cDNA encodes a 775-amino acid protein that has a partial homology with necdin at the C terminus and 25 repeats of hexapeptides (WQXPXX) in the middle region. Dlxin-1 mRNA is expressed in various adult tissues, but not the spleen, and also in osteoblastic and chondrogenic cell lines. During embryogenesis, a strong signal for Dlxin-1 mRNA was found in cell layers surrounding cartilaginous elements in bone rudiment during digit formation. Dlxin-1 binds not only Dlx5 but also Dlx7 and Msx2 and forms homomultimers in vivo. Transfection and reporter gene assays indicate that Dlxin-1 activates the transcriptional function of Dlx5. Therefore, Dlxin-1 may act as a regulator of the function of Dlx family members in bone formation.

Amino Acid Sequence↗
PubMed2000

Host-parasite coevolution in a multilocus gene-for-gene system.

This paper examines a mathematical model for the coevolution of parasite virulence and host resistance under a multilocus gene-for-gene interaction. The degrees of parasite virulence and host resistance show coevolutionary cycles for sufficiently small costs of virulence and resistance. Besides these coevolutionary cycles of a longer period, multilocus genotype frequencies show complex fluctuations over shorter periods. All multilocus genotypes are maintained within host and parasite classes having the same number of resistant/virulent alleles and their frequencies fluctuate with approximately equally displaced phases. If either the cost of virulence or the number of resistance loci is larger then a threshold, the host maintains the static polymorphism of singly (or doubly or more, depending on the cost of resistance) resistant genotypes and the parasite remains universally avirulent. In other words, host polymorphism can prevent the invasion of any virulent strain in the parasite. Thus, although assuming an empirically common type of asymmetrical gene-for-gene interaction, both host and parasite populations can maintain polymorphism in each locus and retain complex fluctuations. Implications for the red queen hypothesis of the evolution of sex and the control of multiple drug resistance are discussed.

Animals↗
PubMed2000

CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2.

The cytokine-inducible SH2 protein-3 (CIS3/SOCS-3/SSI-3) has been shown to inhibit the JAK/STAT pathway and act as a negative regulator of fetal liver erythropoiesis. Here, we studied the molecular mechanisms by which CIS3 regulates the erythropoietin (EPO) receptor (EPOR) signaling in erythroid progenitors and Ba/F3 cells expressing the EPOR (BF-ER). CIS3 binds directly to the EPOR as well as JAK2 and inhibits EPO-dependent proliferation and STAT5 activation. We have identified the region containing Tyr(401) in the cytoplasmic domain of the EPOR as a direct binding site for CIS3. Deletion of the Tyr(401) region of the EPOR reduced the inhibitory effect of CIS3, suggesting that binding of CIS3 to the EPOR augmented the negative effect of CIS3. Both N- and C-terminal regions adjacent to the SH2 domain of CIS3 were necessary for binding to EPOR and JAK2. In the N-terminal region of CIS3, the amino acid Gly(45) was critical for binding to the EPOR but not to JAK2, while Leu(22) was critical for binding to JAK2. The mutation of G45A partially reduced ability of CIS3 to inhibit EPO-dependent proliferation and STAT5 activation, while L22D mutant CIS3 was completely unable to suppress EPOR signaling. Moreover, overexpression of STAT5, which also binds to Tyr(401), reduced the binding of CIS3 to the EPOR, and the inhibitory effect of CIS3 against EPO signaling, while it did not affect JAB/SOCS-1/SSI-1. These data demonstrate that binding of CIS3 to the EPOR augments the inhibitory effect of CIS3. CIS3 binding to both EPOR and JAK2 may explain a specific regulatory role of CIS3 in erythropoiesis.

Animals↗
PubMed2000

Abdominal vagi mediate c-Fos expression induced by X-ray irradiation in the nucleus tractus solitarii of the rat.

The mechanism of induction of emesis by X-ray irradiation remains largely unknown. The purpose of the present research was to clarify the neuronal basis of the induction of nausea induced by X-ray irradiation analyzing c-Fos expression in the nucleus tractus solitarii (NTS) as a marker of cellular excitation. We confirmed that the dose of X-ray irradiation (4 Gy) used for the present research could actually induce nausea by preliminary measurement of kaolin intake. Induction of c-Fos immunoreactivity in the NTS was observed in the animals that received X-ray irradiation of the whole body. The mean number of c-Fos positive cells in the animals that received irradiation was significantly larger than that in the non-irradiated animals. Partial exposure of the abdomen to X-rays showed significantly greater c-Fos expression than that of the head. These results indicated the presence of a certain route for transmitting information from the periphery toward the central nervous system by X-ray irradiation. The number of c-Fos positive cells induced by X-ray irradiation in animals vagotomized at the subdiaphragmatic level was lower than that in sham-operated animals. Animals receiving a serotonin subtype three (5-HT3, 5-hydroxytryptamine) receptor antagonist (tropisetron, ICS 205-930, 3-tropanyl-indole-3-carboxylate) showed a significant reduction in c-Fos protein expression compared to animals receiving a vehicle. These results strongly suggested that X-ray irradiation activates 5-HT3 receptors on the terminals of the abdominal vagal nerves to excite the afferent pathway, thereby inducing emesis.

Abdomen↗
PubMed2000

The evolution of parasite virulence and transmission rate in a spatially structured population.

If the transmission occurs through local contact of the individuals in a spatially structured population, the evolutionarily stable (ESS) traits of parasite might be quite different from what the classical theory with complete mixing predicts. In this paper, we theoretically study the ESS virulence and transmission rate of a parasite in a lattice-structured host population, in which the host can send progeny only to its neighboring vacant site, and the transmission occurs only in between the infected and the susceptible in the nearest-neighbor sites. Infected host is assumed to be infertile. The analysis based on the pair approximation and the Monte Carlo simulation reveal that the ESS transmission rate and virulence in a lattice-structured population are greatly reduced from those in completely mixing population. Unlike completely mixing populations, the spread of parasite can drive the host to extinction, because the local density of the susceptible next to the infected can remain high even when the global density of host becomes very low. This demographic viscosity and group selection between self-organized spatial clusters of host individuals then leads to an intermediate ESS transmission rate even if there is no tradeoff between transmission rate and virulence. The ESS transmission rate is below the region of parasite-driven extinction by a finite amount for moderately large reproductive rate of host; whereas, the evolution of transmission rate leads to the fade out of parasite for small reproductive rate, and the extinction of host for very large reproductive rate.

Animals↗
PubMed2000

Age-related amyloid beta protein accumulation induces cellular death and macrophage activation in transgenic mice.

In view of the importance of amyloid beta protein accumulation in Alzheimer's disease, this paper examines age-related amyloid beta protein (Abeta) deposition and accompanying cellular changes in a mouse model in vivo. Transgenic mice were studied which expressed a gene encoding 18 residues of signal peptide and 99 residues of the carboxyl-terminal fragment (CTF) of the Abeta precursor, under the control of the cytomegalovirus enhancer/chicken beta-actin promoter. In the pancreas, Abeta accumulated in an age-dependent manner. Abeta deposits appeared as early as 3 weeks of age and increased in size and number from 4 to 16 months of age. The largest Abeta deposits were observed in the transgenic pancreas at 16 and 20 months of age. Haematoxylin and eosin staining, macrophage immunostaining, and electron microscopy showed that the Abeta fibril deposits closely correlated with degeneration of pancreatic acinar cells and macrophage activation. Abeta1-42 and Abetap3E-42 were predominant components of Abeta deposits among amino- and carboxyl-terminal modified Abeta species. These findings suggest that overproduction of Abeta causes age-related accumulation of Abeta fibrils, with accompanying cellular degeneration and macrophage activation in vivo.

Aging↗
PubMed2000

Histopathological and physiological characteristics of cultured human ACTH-secreting cells derived from a rapidly growing pituitary adenoma.

We observed the histopathological and physiological characteristics of adrenocorticotropic hormone (ACTH)-secreting adenoma cells derived from a rapidly growing pituitary adenoma, which have firm cell attachment and well-preserved hormonal function in a relatively longterm culture. Corticotrophs, obtained from a 43-year-old woman with Cushing's disease in whom plasma ACTH levels increased in response to 1-deamino-8-D-arginine vasopressin (DDAVP) stimulation and the proliferative potential was very high, were grown in tissue culture for up to 6 months. The morphological features were observed by phase contrast and electron microscopy. The cultured cells were incubated with corticotroph-releasing hormone (CRH), arginine vasopressin (AVP), or DDAVP, and ACTH in the medium was measured by radioimmunoassay (RIA). The morphology of the ACTH-secreting adenoma cells in culture revealed a mixed population of formed clusters and spindle-shaped fibroblast-like cells. The adenoma cells were immunohistochemically positive only for ACTH. On electron microscopic observation, pituitary tumor cells obtained 6 days after seeding demonstrated many secretory granules, well-developed rough endoplasmic reticulum, and mitochondria; fewer secretory granules were observed after cultivation for 24 days. ACTH levels in the incubation media were elevated with stimulation by DDAVP, AVP, or CRH. In this study, the establishment of relatively longterm culture of human pituitary adenoma cells seemed to be due to the high proliferative potential of this adenoma. This in vitro study may imply that DDAVP as well as AVP directly stimulates ACTH release from corticotropic adenoma cells.

Adenoma↗
PubMed2000

Acute aortic thrombosis after intra-aortic balloon pumping.

Acute aortic occlusion is a rare but devastating complication of intra-aortic balloon pumping. Prompt diagnosis of aortic occlusion and immediate therapeutic decision making are keys for saving patients in such cases. We describe a 72-year-old man who underwent emergency surgical removal of a thrombus and aortoiliac bifurcated grafting for acute aortic occlusion after withdrawal of the intra-aortic balloon pumping catheter. The presence of a small unrecognized abdominal aortic aneurysm was considered to be the cause of thrombosis in this patient. Ultrasonographic screening for an abdominal aortic aneurysm is recommended for patients who require intra-aortic balloon pumping support.

Acute Disease↗
PubMed2000

Minimally invasive direct coronary artery bypass grafting in a patient with brainstem infarction.

Brainstem infarction associated with the primitive trigeminal artery is rare. We describe the case of a 61-year-old man with an acute myocardial infarction as well as a brainstem infarction. The patient was referred for coronary artery bypass grafting. Minimally invasive direct coronary artery bypass grafting (left internal thoracic artery to the second diagonal branch anastomosis) could be safely performed 10 weeks after an episode of brainstem infarction.

Brain Stem↗
PubMed2000

Two autopsy cases with Pelizaeus-Merzbacher disease phenotype of adult onset, without mutation of proteolipid protein gene.

We report the autopsy cases of two brothers which are pathologically compatible with Pelizaeus-Merzbacher disease (PMD). Both patients had a late onset (at the ages of 29 and 42 years) and chronic neurological symptoms including tremor, ataxia and dementia. The T2-weighted magnetic resonance imaging of the younger brother demonstrated increased signal areas with sparing of small areas in the cerebral white matter. The postmortem examinations, obtained at the ages of 45 and 61 years, showed similar neuropathological findings. Histologically, a cardinal finding was a lack of myelin in large parts of white matter with the preservation of islands of intact myelin, resulting in a "tigroid" appearance. Only small amounts of sudanophilic material were present. The axons were relatively well preserved, but oligodendrocytes were numerically reduced. Ultrastructurally, myelin sheaths in the white matter were markedly thin. Immunohistochemistry showed that proteolipid protein (PLP) was reduced in the affected white matter. However, genetic studies did not reveal exonic mutations or duplications of the PLP gene. We conclude that the two cases are a rare type of dysmyelinating disorder with PMD phenotype of adult onset and could be caused by previously unrecognized abnormalities of the PLP gene or other genes.

Adult↗
PubMed2000

Antigenic drift of viruses within a host: a finite site model with demographic stochasticity.

We theoretically study the antigenic drift of viruses within an infected host, as observed in human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) infections, assuming that a finite number of antigen-determining sites at the viral envelop gene are responsible for the specific immune response. The pattern of antigen evolution becomes more complex than that predicted from the previous one-dimensional antigen space models. If the viral growth rate is sufficiently large, the demographic stochasticity for the fate of a new antigen mutant can be neglected. The high dimensionality in the way a virus escapes the immune defense in genotype space could then causes a rapid increase in the antigenic diversity and the total viral density, until finally the whole antigen genotypes are used up. The viral population is then driven to extinction in a host by the enhanced immune response to all genotypes. In contrast, if the viral growth rate is moderate or small so that only a small fraction of new antigen mutants can survive during the initial endangered period of random extinction, the viral antigenic diversity and the total density remain bounded, thereby enabling them to persist for a prolonged period by shifting the dominant antigen types. The phylogenetic pattern of antigen divergence is well characterized by the mean number of surviving antigen mutants from an antigen genotype. The substitution rate at antigen-determining sites increases as the efficiency of host immune response increases.

Animals↗
PubMed2000

The role of caspase family protease, caspase-3 on cisplatin-induced apoptosis in cisplatin-resistant A431 cell line.

PURPOSE: Cisplatin (cis-diamminedichloro-platinum(II), CDDP) has been reported to induce apoptosis in cancer cells. the mechanism of the apoptosis in cancer cells induced by CDDP is still unclear. Recent studies have revealed that caspase family of cystine proteases play an important role in the regulation of several apoptotic processes. In this study, whether apoptosis induced by CDDP could be mediated by the activation of caspase-3, a caspase family protease, was investigated. METHODS: The CDDP-resistant subline A431/CDDP2 from the previously established human epidermoid carcinoma cell line A431 was used. The parent A431 cells (A431/P) and the A431/CDDP2 were exposed to CDDP with or without a caspase family protease inhibitor (Z-Asp-CH2-DCB), and cellular sensitivity to CDDP was determined. DNA fragmentation was then analyzed, and the caspase-3 protein levels determined by Western blotting following exposure of the cells to CDDP with or without Z-Asp-CH2-DCB. RESULTS: In the A431/P cells, the cytotoxicity of CDDP was clearly reduced by Z-Asp-CH2-DCB compared with its cytotoxicity in A431/CDDP2 cells. Furthermore, quantitative analysis of DNA fragmentation revealed that Z-Asp-CH2-DCB inhibited DNA fragmentation induced by CDDP in A431/P cells, but not in A431/CDDP2 cells. Western blotting analysis demonstrated a marked reduction in procaspase-3 protein levels in A431/P cells treated with Z-Asp-CH2-DCB. In the A431/CDDP2 cells, procaspase-3 protein levels were no different with and without Z-Asp-CH2-DCB. CONCLUSIONS: These findings suggest that caspase-3 may mediate apoptosis induced by CDDP, and its induction could represent a novel approach to the effective treatment of malignant tumors.

Antineoplastic Agents↗
PubMed2000

Internal hernia with triple hiatus of congenital origin: report of a case.

We report herein the case of a 65-year-old woman who was referred to our department with prolonged ileus symptoms despite conservative therapy. A plain abdominal radiograph showed intestinal gas shadows with an air-fluid level in the lesser curvature of the stomach. As no improvement was achieved by the insertion of a short tube, a long tube was inserted. A loop formation of the long tube in the subphrenic region was detected on an abdominal radiograph, and an enterogram showed an interruption in the ileum in the lower abdomen. The patient was diagnosed as having an adhesional ileus and a strangulated ileus due to a lesser sac hernia. A laparotomy was performed which revealed that the small intestine had herniated into the lesser sac space through a hiatus of Treitz' fossa and a hiatus in the transverse mesocolon. Furthermore, part of the small intestine had herniated through an omental hiatus. The herniated intestine was manually reduced and the hiatus was closed. However, as the right ovary was found to have adhered to the ileum and stenosis was seen, we were forced to perform partial resection of the ileum. Considering that this patient had no history of laparotomy in the upper abdomen, abdominal injury, or acute abdomen, it was surmised that the three abnormal hiatuses were congenital.

Aged↗
PubMed2000

Percutaneous vertebral angioplasty before coronary artery bypass grafting.

We report a case of a 63-year-old male with three-vessel coronary heart disease complicated by stenosis of the bilateral vertebral arteries. Triple coronary bypass grafting, using arterial conduits, was successfully performed after percutaneous balloon angioplasty of the left vertebral artery. Precedent angioplasty of a stenotic vertebral artery is safe and protects the brain from ischemia during extracorporeal circulation.

Angioplasty, Balloon↗
PubMed2000

Human anti-murine antibodies interfere with CPR assays performed with commercial kits.

Quantitation of C-peptide is important for the assessment of insulin secretion, in particular in patients receiving insulin therapy. Since the CPR levels become much higher than the concentration of C-peptide for several reasons, such as the high concentration of proinsulin, CPR values sometimes need to be assessed carefully. We have had two diabetic patients whose CPR values were abnormally high when determined with a Daiichi C-peptide kit III (method 1). CPR values determined by other methods were from two to ten times lower, indicating considerable interference when method 1 was used. Since method 1 uses mouse monoclonal antibodies (mmab) for detection antibodies, we suspected that human anti-murine antibodies (HAMA) were responsible for the interference. HAMA were detected in serum from both patients (45 and 460 ng/ml in case 1 and case 2 (at peak), respectively). Removal of HAMA from serum eliminated the interference. Modification of method 1 to exclude mmab from the assay system removed all interference. HAMA were, therefore, considered to be the cause of the interference. In case 2, the peak concentration of HAMA was recorded 16 months earlier than the maximum of interference. Further analysis revealed that HAMA with high affinities were responsible for the interference.

Aged↗
PubMed2000

Initial experience with a refractive multifocal intraocular lens in a Japanese population.

PURPOSE: To evaluate a poly(methyl methacrylate) refractive, zonal-progressive multifocal intraocular lens (IOL) in patients requiring cataract surgery. SETTING: Department of Ophthalmology, Saiseikai Kurihashi Hospital, Saitama, Japan. METHODS: This open-label noncomparative study evaluated 58 eyes of 31 Japanese patients who had cataract surgery and implantation of a multifocal IOL (Array(R) PA154N, Allergan Surgical). The main outcome measures were visual acuity (VA) (distance and near, with and without correction), glare disability, and contrast sensitivity (CS) (distance and near, with and without glare under day and night conditions). A questionnaire was used to evaluate the effectiveness of the multifocal IOL. RESULTS: Uncorrected distance VA was 0.7 or better (20/30) in 56 eyes (97.0%) and uncorrected near VA, 0.5 or better (20/40) in 52 eyes (89.7%). Corrected distance VA was 0.7 or better in all eyes. Near VA with distance correction was 0.5 or better in 51 eyes (87.9%). Daytime CS was within the normal range. However, nighttime CS with central glare for both distance and near was markedly decreased. Under all conditions, distance CS was significantly better than near CS from middle- to high-frequency areas. Seventy-four percent of patients with the IOL in both eyes did not need glasses for daily activities, and the others needed glasses only to read for long periods. CONCLUSIONS: The results indicate that this refractive multifocal IOL is distance dominant and is beneficial in Japanese patients. However, since there are differences between Western countries and Japan in distance reading of characters and letters, further modification of this multifocal IOL may be required for use in Japanese patients.

Aged↗