Biomedical subjects

Akira Sasaki

Publications and source records attributed to Akira Sasaki.

16 recordsLinked to original sources

PubMed2003

Mutation landscapes.

A traditional picture of evolutionary dynamics with constant fitness is that of genomes living in sequence space and adapting on fitness landscapes. Mutation rates are considered to be constant or externally regulated. If, however, we take into account that genomes also encode for enzymes that perform replication and error correction, then individual genomes not only have a specific replication rate (fitness), but also a specific mutation rate. This leads to the concept of a mutation landscape. We explore evolution on mutation landscapes. Localization in pure mutation landscapes is only possible under extremely restrictive conditions. Coupling of mutation landscapes and fitness landscapes leads to localization and hence adaptation and evolution. We analyse how mutation landscapes facilitate localization in fitness landscapes and vice versa. Finally, we show that for mutation landscapes, at equilibrium, with constant environment, there is not necessarily selection for the minimum mutation rate. Instead, the target of selection is an optimum distribution of mutation rates, a 'mutational quasispecies'.

Animals↗

PubMed2003

Can transitive inference evolve in animals playing the hawk-dove game?

What should an individual do if there are no reliable cues to the strength of a competitor when fighting with it for resources? We herein examine the evolutionarily stable strategy (ESS) in the hawk-dove game, if the opponent's resource-holding potential (RHP) can only indirectly be inferred from the outcome of past interactions in the population. The strategies we examined include the classical mixed strategy in which no information on past games is utilized, the 'imprinting' strategy in which a player increases/decreases its aggressiveness if it wins/loses a game, the 'immediate inference' strategy in which a player can infer the strength of those opponents it fought before, and the 'transitive inference' strategy in which a player can infer the strength of a new opponent through a third party with which both players have fought before. Invasibility analysis for each pair of strategies revealed that (i) the transitive-inference strategy can always invade the mixed strategy and the imprinting strategy, and itself refuses invasion by these strategies; (ii) the largest advantage for transitive inference is achieved when the number of games played per individual in one generation is small and when the cost of losing an escalated game is large; (iii) the immediate inference, rather than the transitive inference, can be an ESS if the cost of fighting is small; (iv) a strong linear ranking is established in the population of transitive-inference strategists, though it does not perfectly correlate to the ranking by actual RHPs. We found that the advantage of the transitive inference is not in its ability to correct a misassessment (it is actually the worst in doing so), but in the ability of quickly lining up either incorrect or correct assessments to form a linear dominance hierarchy.

Animals↗

PubMed2003

Combination chemotherapy of paclitaxel and cisplatin induces apoptosis with Bcl-2 phosphorylation in a cisplatin-resistant human epidermoid carcinoma cell line.

PURPOSE: Paclitaxel (Taxol, TXL) is an antimicrotubule agent that stabilizes microtubules, arrests the cell cycle at the G(2)/M phase and induces apoptosis. In vitro drug sensitivity assays have shown that the combination of TXL and CDDP is more effective in CDDP-resistant ovarian carcinoma cell lines, with different cytotoxicities depending on the sequence of drug exposure. CDDP also shows poor results in human epidermoid carcinoma particularly of the head and neck region. METHODS: We investigated the effects and the molecular mechanisms of combination chemotherapy with TXL and CDDP in the CDDP-resistant cell line A431/CDDP2, and in its parental human epidermoid cell line A431/P. Drug sensitivity was determined using the MTS assay and cell cycle perturbation was analyzed using flow cytometry. DNA fragmentation was then analyzed and the protein levels of caspase-3 and Bcl-2, and phosphorylated of Bcl-2 were determined by Western blotting. RESULTS: In the drug sensitivity assay, exposure to CDDP prior to TXL was more effective than exposure TXL prior to CDDP in A431/P cells. In A431/CDDP2 cells, exposure to TXL prior to CDDP was more effective than exposure to CDDP prior to TXL. Exposure to TXL arrested the cells in the G(2)/M phase in both cell lines. In A431/CDDP2 cells, exposure to TXL prior to CDDP arrested the cells in the G(2)/M phase, an effect caused by either CDDP or TXL. Analysis of DNA fragmentation showed similar results to the drug sensitivity assay. Expression of caspase-3 protein active form was detected following exposure to TXL only and to the TXL/CDDP combination in both A431/P and A431/CDDP2 cells, but phosphorylation of Bcl-2 protein was detected only following exposure to TXL and only in A431/CDDP2 cells. CONCLUSIONS: These results indicate that exposure to TXL prior to CDDP plays a key role in circumventing CDDP resistance by phosphorylating Bcl-2 protein in the human epidermoid carcinoma cell line A431/CDDP2.

Antineoplastic Agents↗

PubMed2003

Expression of vascular endothelial growth factor-C predicts regional lymph node metastasis in early oral squamous cell carcinoma.

The purpose of this study was to investigate the association of the expression of vascular endothelial growth factor-C (VEGF-C) with regional lymph node metastasis in oral squamous cell carcinoma (OSCC). The expression of VEGF-C in biopsy specimens obtained from 62 patients with OSCC was examined by immunohistochemistry. In the early stages of T1 and T2 (38 cases), VEGF-C expression strongly correlated with lymph node metastasis (P < 0.001), and the percentage of VEGF-C-positive staining was 88.2% for patients with lymph node metastasis (15 of 17 cases) and 28.6% for those without lymph node metastasis (6 of 21 cases). However, in the advanced stages of T3 and T4, no significant correlation between VEGF-C expression and lymph node metastasis was observed. These results indicate that VEGF-C expression in biopsy specimens can be used as a reliable predictor of regional lymph node metastasis, particularly in early OSCC, and may become an important factor in the selection of appropriate treatment.

Aged↗

PubMed2003

Reversible bilateral vestibular impairment caused by fourth ventricle epidermoid tumor.

A 26-year-old man presented with an epidermoid tumor of the fourth ventricle manifesting as headache with nausea and vertigo. Neurological examination revealed no cerebellar signs, except nystagmus. Bilateral vestibular impairment was identified by the caloric test. The tumor was removed via the midline suboccipital approach. The bilateral peripheral vestibular function recovered remarkably postoperatively. This marked improvement suggests that the bilateral vestibular impairment was caused by compression of the vestibular nuclei by the tumor.

Adult↗

PubMed2002

Noisy clues to the origin of life.

The origin of stable self-replicating molecules represents a fundamental obstacle to the origin of life. The low fidelity of primordial replicators places restrictions on the quantity of information encoded in a primitive nucleic acid alphabet. Further difficulties for the origin of life are the role of drift in small primordial populations, reducing the rate of fixation of superior replicators, and the hostile conditions increasing developmental noise. Thus, mutation, noise and drift are three different stochastic effects that are assumed to make the evolution of life improbable. Here we show, to the contrary, how noise present in hostile early environments can increase the probability of faithful replication, by amplifying selection in finite populations. Noise has negative consequences in infinite populations, whereas in finite populations, we observe a synergistic interaction among noise sources. Hence, two factors formerly considered inimical to the origin of life-developmental noise and drift in small populations-can in combination give rise to conditions favourable to robust replication.

Biological Evolution↗

PubMed2002

Modeling host-parasite coevolution: a nested approach based on mechanistic models.

In this study we introduce a mechanistic framework for modeling host-parasite coevolution using a nested modeling approach. The first step in this approach is to construct a mechanistic model of the parasite population dynamics within a host. The second step is to define an epidemiological model which is used to derive the fitness functions for both the host and the parasite. The within-host model is then nested within the epidemiological model by linking the epidemiological parameters such as the transmission rate of the infection or the additional host mortality rate to the dynamics of the within-host model. Nesting the within-host model into an epidemiological model allows us to evaluate the fitness functions for each interactor which in turn allows us to determine the coevolutionary dynamics of the system. This nested approach has the advantage over other approaches in that mechanistic descriptions of the host-parasite biology are used to derive, rather than impose, life-history trade-offs. We illustrate this framework by analysing a simple host-parasite system. In this particular system we find that the coevolutionary equilibrium is always stable and that host survivorship and parasite fitness vary greatly with the cost of the immune response and parasite growth.

Animals↗

PubMed2002

Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects.

We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects.

Adolescent↗

PubMed2002

Spatial mosaic and interfacial dynamics in a Müllerian mimicry system.

Uncovering why spatial mosaics of mimetic morphs are maintained in a Müllerian mimicry system has been a challenging issue in evolutionary biology. In this article, we analyze the reaction diffusion system that describes two-species Müllerian mimicry in one- and two-dimensional habitats. Due to positive frequency-dependent selection, a local population first approaches the state where one of the comimicking patterns predominates, which is followed by slow movement of boundaries where different patterns meet. We then analyze the interfacial dynamics of the boundaries to find whether a stable cline is maintained and to obtain the wave speed if the cline is unstable. The results are: (1) In a spatially uniform habitat the morph with greater base fitness spreads both in one and two species system. (2) The strength of cross-species interaction determines whether the mimetic morph clines of model and mimic species coalesce into the same geographical region or pass through each other. The joint wave speed of clines decreases by increasing the number of comimicking species in the mimicry ring. (3) In spatial heterogeneous habitats, stable clines can be maintained due to the balance between the base fitness gradient and the biased gene flow by negative curvature of boundary. This allows the persistence of a spatial mosaic even if one of the morphs is in every place advantageous over the other. A balanced cline is also maintained if there is a gradient in the population density. (4) A new advantageous morph occurring at a local region is doomed to go to extinction in a finite time if the "radius" of initial distribution is below a threshold. Possible applications to the heliconiine butterfly mimicry ring, heterozygous disadvantage systems of chromosomal rearrangement and hybrid zone, the third phase of Wright's Shifting Balance theory, and cytoplasmic incompatibility are discussed.

Animals↗

PubMed2002

Report of the Committee on the classification and diagnostic criteria of diabetes mellitus.

In 1995, the Japan Diabetes Society (JDS) appointed the Committee for the Classification and Diagnosis of Diabetes Mellitus. The Committee presented a final report in May 1999 in Japanese. This is the English version with minor modifications for readers outside Japan. CONCEPT OF DIABETES MELLITUS: Diabetes mellitus represents a group of diseases of heterogeneous etiology, characterized by chronic hyperglycemia and other metabolic abnormalities, which are due to deficiency of insulin effect. After a long duration of metabolic derangement, specific complications of diabetes (retinopathy, nephropathy, and neuropathy) may occur. Arteriosclerosis is also accelerated. Depending on the severity of the metabolic abnormality, diabetes may be asymptomatic, or may be associated with symptoms (thirst, polyuria, and weight loss), or may progress to ketoacidosis and coma. CLASSIFICATION: Both etiological classification and staging of pathophysiology by the degree of deficiency of insulin effect need to be considered. The etiological classification of diabetes and related disorders of glycemia includes, (1) type 1; (2) type 2; (3) those due to specific mechanisms and diseases; and (4) gestational diabetes mellitus. Type 1 is characterized by destructive lesions of pancreatic beta cells either by an autoimmune mechanism or of unknown cause. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Category (3) includes two subgroups; subgroup A is diabetes in which specific mutations have been identified as a cause of genetic susceptibility, while subgroup B is diabetes associated with other pathologic conditions or diseases. The staging of glucose metabolism includes normal, borderline and diabetic stages. The diabetic stage is further classified into three substages; non-insulin requiring, insulin-requiring for glycemic control, and insulin-dependent (ID) for survival. In each individual, these stages may vary according to the deterioration or the improvement of the metabolic state, either spontaneously or by treatment. DIAGNOSIS: The confirmation of chronic hyperglycemia is a prerequisite for the diagnosis of diabetes mellitus. The state of glycemia may be classified within three categories, diabetic type; borderline type; and normal type. Diabetic type is defined when fasting plasma glucose (FPG) is 7.0 mmol/l (126 mg/dl) or higher, and/or plasma glucose 2 h after 75 g glucose load (2hPG) is 11.1 mmol/l (200 mg/dl) or higher. A casual plasma glucose (PG) > or =11.1 mmol/l (200 mg/dl) also indicates diabetic type. Normal type is defined when FPG is below 6.1 mmol/l (110 mg/dl) and 2hPG below 7.8 mmol/l (140 mg/dl). Borderline type includes those who are neither diabetic nor normal types. These cutoff values are for venous PG measurements. The persistence of 'diabetic type' in a subject indicates that he or she has diabetes. For children, a dose of 1.75 g/kg (maximum, 75 g) is used for oral glucose tolerance test (OGTT). The procedure for clinical diagnosis is as follows. Diabetes mellitus is diagnosed when hyperglycemia meeting the criteria for 'diabetic type' is shown on two or more occasions examined on separate days. Diabetes can be diagnosed by a single PG test of 'diabetic type' if one of the following three conditions co-exists, (1) typical symptoms of diabetes mellitus; (2) HbA1c > or =6.5% by a standardized method; or (3) unequivocal diabetic retinopathy. If the above conditions ((1) or (2)) have been present in the past and well documented, the subject is diagnosed either to have diabetes or to be suspected of diabetes, even if the present level of glycemia does not reach that of 'diabetic type'. If the diagnosis of diabetes cannot be established by these procedures, re-testing of PG is recommended after an appropriate interval. The physician should assess not only the presence or absence of diabetes, but also its etiology and glycemic stage, and the presence and absence of diabetic complications or associated conditions. EPIDEMIOLOGICAL ASPECTS AND SCREENING: In order to determine the prevalence of diabetes in a population, 'diabetic type' may be regarded as 'diabetes'. The use of 2hPG cutoff level of > or =11.1 mmol/l (200 mg/dl) is recommended. If this is difficult, the FPG cutoff level of > or =7.0 mmol/l (126 mg/dl) can be used, but is likely to lead to under-ascertainment. For screening, the most important point is not to overlook 'diabetes'. In addition to parameters of hyperglycemia, clinical information such as family history, obesity etc., should be regarded as indications for further testing. NORMAL TYPE AND BORDERLINE: Only FPG and 2hPG are adopted as cutoff values, but in clinical situations, it is recommended to measure PG also at 30 and 60 min during 75 g OGTT. Among people with normal type, those with 1hPG higher than 10.0 mmol/l (180 mg/dl) are at higher risk to develop diabetes than those with lower 1hPG. When OGTT is performed, the borderline type corresponds to the sum of impaired fasting glycemia (IFG) plus impaired glucose tolerance (IGT) according to the new WHO report. Subjects in this category are at higher risk of developing diabetes than those with 'normal type'. Those with low insulinogenic index (the ratio of increment of plasma insulin to that of PG at 30 min during OGTT) are at particularly high risk to develop diabetes. Microvascular complications are rare but arteriosclerotic complications are fairly frequent in this category. GESTATIONAL DIABETES MELLITUS (GDM): The current definition of GDM is ' any glucose intolerance developed or detected during pregnancy'. We adopt the proposal of the Japan Society of Gynecology and Obstetrics for the diagnosis of GDM (1984). GDM is defined when two or more values during a 75 g OGTT are higher than the following cutoff levels; FPG > or =5.5 mmol/l (100 mg/dl), 1hPG > or =10.0 mmol/l (180 mg/dl) and 2hPG > or =8.3 mmol/l (150 mg/dl). As a screening test, subjects with casual PG > or =5.5 mmol/l (100 mg/dl) are recommended for further testing. Patients who have had documented glucose intolerance before pregnancy, and who present as 'diabetic type' should be under closer supervision than those who develop GDM during pregnancy for the first time. HbA1c: There is a large overlap in the distribution of HbA1c between groups with 'normal type' and 'borderline type' and mild 'diabetic type'. Therefore, HbA1c is not a suitable parameter to detect mild glucose intolerance. HbA1c higher than 6.5% suggests diabetes, but HbA1c below 6.5% alone should not be taken as evidence against the diagnosis of diabetes. COMPARISON WITH REPORTS OF AMERICAN DIABETES ASSOCIATION (ADA) IN 1997 AND WHO IN 1999: The present report is unique in the following points when compared with those of the ADA 'Diabetes Care 20 (1997) 1183' and WHO 'Report of a WHO Consultation (1999)'. (1) Diabetes due to specific mechanisms and diseases is divided into two subgroups; diabetes in which genetic susceptibility is clarified at the DNA level and diabetes associated with other diseases or conditions. (2) Cutoff PG levels are the same as those of ADA and WHO, but a term 'type' is added to each glycemic category, because a single coding of 'diabetic type' hyperglycemia does not define diabetes. Diabetes is diagnosed when 'diabetic type' hyperglycemia is shown on two or more occasions. (3) A single 'diabetic type' hyperglycemia is considered sufficient for the diagnosis of diabetes, if the patient has typical symptoms, HbA1c > or =6.5%, or diabetic retinopathy. (4) OGTT is recommended for those with mild hyperglycemia, because FPG criteria alone would overlook many subjects with 'diabetic type' in Japan. High 1hPG without elevation of FPG and 2hPG is also considered to be a risk factor for future diabetes. (5) Borderline type in the present report corresponds to the sum of IFG and IGT by WHO when OGTT is performed. (6) New criteria for GDM by OGTT are proposed.

Blood Glucose↗

PubMed2002

A comparative study of odontogenic keratocysts associated with and not associated with an impacted mandibular third molar.

OBJECTIVE: The purpose of this study was to compare odontogenic keratocysts associated with and not associated with an impacted mandibular third molar. STUDY DESIGN: Panoramic radiographs of odontogenic keratocysts associated with impacted mandibular third molars (15 cysts, associated group) were compared with radiographs of odontogenic keratocysts not associated with impacted mandibular third molars (25 cysts, nonassociated group). The radiographic images were analyzed with reference to the patients' age and sex. RESULTS: The mean age of patients in the associated group was lower than that of patients in the nonassociated group. The mean area of the cysts in the associated group was larger than that of those in the nonassociated group. The patients' ages did not significantly correlate to the areas of either kind of cyst. CONCLUSIONS: The odontogenic keratocysts in the associated group had a tendency toward rapid growth in the patients' youth.

Adolescent↗

PubMed2002

Endoscopic versus conventional open thyroid lobectomy for benign thyroid nodules: a prospective study.

The current study compared results between endoscopic thyroidectomy and conventional surgery in a prospective study. Twenty-two patients eligible for endoscopic thyroidectomy were evaluated. Patients were divided into group A, for conventional open thyroidectomy (n = 12), and group B, for endoscopic thyroidectomy (n = 10). Operative time, blood loss, postoperative complications and analgesic requirements, and time taken to return to normal activity were compared. Groups A and B were statistically balanced. Blood loss was significantly less in group B than in group A (11 versus 32 mL; P = 0.004), but no significant differences were observed in any of the other parameters. No postoperative complications (hemorrhage or recurrent laryngeal nerve paralysis) were present in either group. Compared with conventional surgery, endoscopic thyroidectomy for benign thyroid nodules was associated with less blood loss, although blood loss was minimal for both procedures. There were no practical differences in technical ability to perform.

Adult↗

PubMed2002

New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems.

Discovery of novel antimicrobial agents effective against infections caused by drug-resistant pathogens is an important objective. In order to find a new parenteral carbapenem antibiotic, which has potent antibacterial activity especially against methicillin-resistant staphylococci, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae, a series of 1beta-methylcarbapenems with thiazol-2-ylthio groups at the C-2 position have been synthesized. Structure-activity relationships were investigated which led to SM-197436 (27), SM-232721 (44) and SM-232724 (41), being selected for further evaluation.

Anti-Bacterial Agents↗

PubMed2002

Dietary bile acids inhibit potentially elemental diet-induced small intestinal atrophy in rats.

The mechanism responsible for elemental diet (ED)-induced small intestinal atrophy is still unknown. However, it is possible that bile acids in the gut lumen influence this process. The aim of this study was to evaluate the effects of oral bile acid administration during ED feeding. Specific pathogen-free male Sprague-Dawley rats, 10 weeks old, were fed an ED only, ED plus 0.1% (w/w) hyocholic acid, or ED plus 0.1% (w/w) hyodeoxycholic acid ad libitum for 4 weeks. The control rats were fed standard chow ad libitum for 4 weeks. After 4 weeks, the wet weight and whole length of the small intestine, and the mucosal diamine oxidase (DAO) and alkaline phosphatase (ALP) activities were measured. Microscopic histological observation was also performed. ED feeding induced atrophy and elevations in the mucosal DAO and ALP activities in the small intestine. Hyocholic acid and hyodeoxycholic acid administration both tended to inhibit these alterations. In conclusion, ED feeding induced atrophy and elevations in the mucosal DAO and ALP activities in the small intestine. Oral bile acid administration may prevent this atrophy and the elevations in mucosal DAO and ALP activities, which may lead to new therapeutic strategies in patients managed with ED.

Administration, Oral↗

PubMed2002

Localization of gamma-aminobutyric acid A receptor subunits in the rat spiral ganglion and organ of Corti.

Gamma-aminobutyric acid (GABA) is thought to be the major inhibitory neurotransmitter in the central nervous system. Although it is distributed in the olivo-cochlear bundles, which constitute the mammalian cochlear efferent system, its function in the cochlea is still obscure. In this study, we investigated the localization of GABAa receptor subunits (alpha1-6, beta1-3, gamma) in the rat cochlea in order to determine the role of GABA in the cochlea. Most spiral ganglion cells were intensely immunolabeled with all the anti-GABAa receptor subunit antibodies. In the organ of Corti, punctate immunoreactivities were observed in inner hair cell regions corresponding to the distribution of GABA. These data suggest that GABAa receptor was present in afferent nerve terminals in inner hair cell regions, and that GABA regulated afferent nerve transmission contacting efferent nerve endings by means of the axo-dendritic synapse function.

Animals↗

PubMedDate not supplied

Prognostic significance of heat shock protein 27 (HSP27) in patients with oral squamous cell carcinoma.

Heat shock proteins (HSPs) have been defined as proteins induced by heat shock and other environmental and pathophysiologic stress. Heat shock protein 27 (HSP27) is one of the small heat shock proteins. HSP27 is implicated in protein-protein interactions such as folding, translocation, and prevention of inappropriate protein aggregation. Many of their functions suggest that they play important roles in cancers. Archival tissues from 40 patients with oral squamous cell carcinoma who received primary surgical resection were examined for HSP27 by immunohistochemistry and correlated with clinical stage, lymph node metastasis, histological grade and survival period. HSP27 expression was positive staining (+) in 20 (50%), weak or negative staining (-) in 20 (50%) of total 40 cases. There was no correlation between HSP27 expression and clinical stage, lymph node metastasis and histological grade. However, when compared with clinicopathological features, the expression of HSP27 correlated inversely with survival period. This study suggests that the expression of HSP27 is frequently promoted in patients with oral squamous cell carcinoma and should be considered an independent prognostic factor of oral squamous cell carcinoma patients.

Aged↗