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Biomedical subjects

K Kawano

Publications and source records attributed to K Kawano.

At least 163 records · Page 9Linked to original sources

Expression of the SART-1 antigens in uterine cancers.

We recently reported that the SART-1 gene, encoding the SART-1(259) tumor antigen which is recognized by HLA-A26-restricted cytotoxic T lymphocytes (CTLs), is expressed in the cytosol of squamous cell carcinomas and adenocarcinomas. The present study deals with the expression of SART-1(259) and SART-1(800) antigens in uterine cancers. The SART-1(259) antigen was detected in the cytosol fraction of 4 of 8 uterine cancer cell lines, 24 of 74 (32%) uterine cancer tissues, 0 of 7 uterine myomas, and 0 of 5 non-tumorous uterine tissues. The SART-1(800) antigen was expressed in the nuclear fraction of all the uterine cancer cell lines, 41 of 74 (55%) uterine cancer tissues, 0 of 7 myomas, and 3 of 5 non-tumorous uterine tissues. The SART-1(259)+ uterine cancer cells were recognized by HLA-A24 restricted and SART-1 specific CTLs. Therefore, SART-1(259) antigen could be an appropriate vaccine candidate for a relatively large number of uterine cancer patients.

Adenocarcinoma↗

Detection of Coxiella burnetii specific DNA in blood samples from Japanese patients with chronic nonspecific symptoms by nested polymerase chain reaction.

The nested polymerase chain reaction (PCR) was used for direct species-specific detection of Coxiella burnetii in blood samples from 52 patients with chronic nonspecific symptoms, but no diagnostic or treatment history of Q fever. All patients had been in ill-health with general fatigue, muscle and joint pain, headache, etc., for one to more than 10 years. Seventeen (33%) showed evidence of C. burnetii infection, based on amplification of 438-bp fragments specific to C. burnetii by nested PCR, and 94% of positive patients reported close contact with animals. In contrast, five (9.6%) of 52 samples from healthy adult controls and two (2.8%) of 70 cord blood samples were positive by nested PCR. These data suggest a high prevalence of infection among adult patients with long term, nonspecific complaints who live in close contact with animals and the possible existence of a chronic post-acute Q fever syndrome in Japan.

Adolescent↗

[Detection of enteroaggregative Escherichia coli from sporadic diarrhea patients].

A study of enteroaggregative Escherichia coli (EAggEC) which was recently reported as a causative agent of diarrhea was attempted, by isolating these organisms from the fecal samples collected from sporadic diarrhea patients in Miyazaki Prefecture during the period from January 1993 to April 1998, and by investigating several characteristics of the isolates. By using the PCR method targetting aggR gene which was a transcriptional activator of aggregative adherence fimbria I expression, thirty four strains of aggR(+)-Escherichia coli (E. coli) were detected from 2,652 fecal samples. Twenty nine of these 34 isolates were confirmed as EAggEC by demonstration of aggregative adherence to HEp-2 cells, and the other 5 isolates were not EAggEC because they showed negative adherence to HEp-2 cells. The above mentioned, aggR-PCR method revealed that there were a few non-EAggEC strains with aggR gene. It has been reported that aggregative adherence fimbriae are encoded by the plasmid of about 60 Md. All of the 29 EAggEC isolates possessed plasmids of about 50 Md or more, and these plasmids were suggested to relate to aggregative adherence fimbriae. Sixteen (55%) of the 29 isolates were classified serologically into two serotypes, O111:H21 and O126:H27, and the other 13 isolates were classified into ten groups or more which included a few strains in a group. EAggEC heat-stable enterotoxin 1 (EAST1) gene was demonstrated in nineteen of 29 isolates. In drug susceptibility test, 72%, 59% and 21% of the 29 isolates showed resistance to Ampicillin, Cefazolin, and Streptomycin, respectively.

Bacterial Adhesion↗

A disrupted cholecystokinin A receptor gene induces diabetes in obese rats synergistically with ODB1 gene.

Otsuka Long-Evans Tokushima fatty (OLETF) rats develop hyperglycemia, hyperinsulinemia, and mild obesity, which are characteristic of human non-insulin-dependent diabetes mellitus. We have shown that two recessive genes, ODB1 mapped on the X chromosome and ODB2 mapped on chromosome 14, are involved in the induction of the diabetes in OLETF rats. Recently we found that OLETF rats are the naturally occurring cholecystokinin type A receptor (CCKAR) gene knockout rats. In this study, we focused on the genotype of CCKAR gene and the ODB1 gene in regulation of glucose homeostasis in the F2 cross of the OLETF rats. Relatively high plasma glucose levels were observed in the F2 offspring with the homozygously disrupted CCKAR gene. A synergistic effect for increasing plasma glucose levels in F2 rats between disrupted CCKAR gene and the ODB1 gene was shown. The CCKAR gene was found to map very close to ODB2 by a linkage analysis using microsatellite markers. These results suggest that CCKAR gene maintains normoglycemia in rats.

Animals↗

Increased cerebral infarction by cyclic flow reductions: studies in the guinea pig MCA thrombosis model.

We have developed a photochemical model of thrombotic middle cerebral artery (MCA) occlusion in the guinea pig for investigating factors contributing to the development of cerebral infarction. In this model, cyclic flow reductions (CFRs) after recanalization of the MCA are a common observation and might contribute to the development of cerebral infarction. Therefore, we sought to measure the time course of recanalization of the guinea pig MCA after the artery had been occluded by a thrombus. Thrombotic occlusion of the MCA was induced by photochemical reaction between intravenously administered rose bengal and transluminal green light for 10, 15, 20, or 30 min. After the thrombotic occlusion of MCA and subsequent spontaneous thrombolysis, blood flow in the MCA gradually recovered to preocclusion level but with frequent CFRs. The recovery of MCA blood flow or duration of CFRs was dependent on the duration of photochemical reaction (extent of endothelial injury); thus, for a 30-min photochemical reaction, CFRs were still observed 24 h after photochemical reaction. In separate experiments, we also investigated the effect of permanent occlusion of the MCA, which was induced by electrocoagulation in the vessel on cerebral infarction. The infarct volume in the permanent occlusion model was smaller than the maximum value in the thrombotic occlusion model (12.5 vs. 17.4%; P < 0.05, n = 6). CFRs may constitute an important factor contributing to the extent of cerebral infarction.

Animals↗

Temporal firing patterns of Purkinje cells in the cerebellar ventral paraflocculus during ocular following responses in monkeys I. Simple spikes.

The simple-spike firing frequency of 30 Purkinje cells (P cells) in the ventral paraflocculus (VPFL) of alert monkeys was studied in relation to vertical slow eye movements, termed ocular following response (OFR), induced by large-field visual motions of different velocities and durations. To quantitatively analyze the relationship between eye movement and firing frequency, an inverse dynamics representation of the eye movement was used for reconstructing the temporal waveform of firing. Coefficients of eye-acceleration, velocity, and position, bias, and time lag between firing and eye movement were estimated by least-square error method. In the regression analyses for each stimulus condition, 86% (146/170) of the well-modulated temporal firing patterns taken from those 30 P cells were reconstructed successfully from eye movement. The model with acceleration, velocity, and position terms, which we used, was shown as the best among several potential models by Cp statistics, consistent with t-test of significance of each term. Reliable coefficients were obtained from 75% (109/146) of the well-reconstructed firing patterns of 28 cells among 30. The estimated coefficients were larger (statistically significant) for slow stimuli than for fast stimuli, suggesting changes in sensitivities under different conditions. However, firing patterns of each cell under several different conditions were frequently well reconstructed by an inverse dynamics representation with a single set of coefficients (13 cells among 21). This indicates that the relationships between P cell firing and OFR are roughly linear in those stimulus ranges. The estimated coefficients for acceleration and velocity suggested that the VPFL P cells properly encode the dynamic components of the motor command during vertical OFR. As for the positional component, however, these P cells are correlated with eye movement in the opposite direction. In the regression analysis without positional component, remarkable differences between observed and reconstructed firing patterns were noted especially in the initial phase of the movements, indicating that the negative positional component was not negligible during OFR. Thus we conclude that, during OFR, the VPFL P cells cannot provide the necessary final motor command, and other brain regions, downstream neural structures, or other types of P cells must provide lacking position-dependent motor commands. This finding about the negative correlation with the position is in the opposite sign with previous studies obtained from the fixation and the smooth pursuit movement. From these comparisons, how the VPFL contributes to a part of the final motor command or how other brain regions complement the VPFL is suggested to be different for early and late phases of the movements.

Action Potentials↗

Temporal firing patterns of Purkinje cells in the cerebellar ventral paraflocculus during ocular following responses in monkeys II. Complex spikes.

Many theories of cerebellar motor learning propose that complex spikes (CS) provide essential error signals for learning and modulate parallel fiber inputs that generate simple spikes (SS). These theories, however, do not satisfactorily specify what modality is represented by CS or how information is conveyed by the ultra-low CS firing rate (1 Hz). To further examine the function of CS and the relationship between CS and SS in the cerebellum, CS and SS were recorded in the ventral paraflocculus (VPFL) of awake monkeys during ocular following responses (OFR). In addition, a new statistical method using a generalized linear model of firing probability based on a binomial distribution of the spike count was developed for analysis of the ultra-low CS firing rate. The results of the present study showed that the spatial coordinates of CS were aligned with those of SS and the speed-tuning properties of CS and SS were more linear for eye movement than retinal slip velocity, indicating that CS contain a motor component in addition to the sensory component identified in previous studies. The generalized linear model to reproduce firing probability confirmed these results, demonstrating that CS conveyed high-frequency information with its ultra-low firing frequency and conveyed both sensory and motor information. Although the temporal patterns of the CS were similar to those of the SS when the sign was reversed and magnitude was amplified approximately 50 times, the velocity/acceleration coefficient ratio of the eye movement model, an aspect of the CS temporal firing profile, was less than that of the SS, suggesting that CS were more sensory in nature than SS. A cross-correlation analysis of SS that are triggered by CS revealed that short-term modulation, that is, the brief pause in SS caused by CS, does not account for the reciprocal modulation of SS and CS. The results also showed that three major aspects of the CS and SS individual cell firing characteristics were negatively correlated on a cell-to-cell basis: the preferred direction of stimulus motion, the mean percent change in firing rate induced by upward stimulus motion, and patterns of temporal firing probability. These results suggest that CS may contribute to long-term interactions between parallel and climbing fiber inputs, such as long-term depression and/or potentiation.

Action Potentials↗

A case of Guillain-Barré syndrome developed minimal change nephrotic syndrome simultaneously.

A case who developed Guillain-Barré syndrome (GBS) and nephrotic syndrome (NS) simultaneously is reported. In this case, the onset of nephrotic change of proteinuria coincided with the development of the neurological disturbance. Analysis of renal biopsy by light, immunofluorescent and electron microscopy showed minor glomerular abnormalities. The occurrence of GBS in association with NS is rare, and moreover most cases in the previous reports had membranous nephropathy. Only 1 case had minimal change nephrotic syndrome (MCNS). To our knowledge, this is the first report of a case beneficially treated with glucocorticoids, suggesting that immune disorder may play an important role in the association between MCNS and GBS.

Adult↗

Targeting of soybean-derived sterylglucoside liposomes to liver tumors in rat and mouse models.

The blood clearance, tissue uptake and antitumor efficacy against liver metastasis of M5076 reticulosarcoma in mice and against primary liver cancer in rats of doxorubicin (DOX) encapsulated in two types of liposomes, with and without a soYbean-derived sterylglucoside mixture (SG), were examined. Liposomes entrapping DOX were composed of dipalmitoylphosphatidylcholine (DPPC), SG and cholesterol (Ch) at a molar ratio of 6:1:3, (SG-liposomes) and 6:0:4 (non-SG-liposomes). Pharmacokinetic analysis of drug disposition was based on the area under the curve (AUC) for liposomes up to 24 h following i.v. injection. SG-liposomes showed lower DOX concentrations in blood and higher concentrations in liver compared with non-SG-liposomes. The highest AUC of SG-liposomes in tissue was in liver, 2.4 times higher than that of the free drug. The antitumor efficacy of SG-liposomes was compared with that of free DOX and non-SG-liposomes at a dose of 5 mg DOX/kg. SG-liposomes displayed stronger antitumor activity than the free drug and non-SG-liposomes in murine reticulosarcoma M5076 tumor models and primary liver cancer models reflecting accumulation in hepatocytes. The antitumor activity of SG-liposomes in rats with primary liver cancer was significantly higher compared with free DOX and non-SG-liposomes (ILS: 92.7%).

Animals↗

CD45RO expression on peripheral lymphocytes as a prognostic marker for adult T-cell leukemia.

Adult T-cell leukemia (ATL) is an aggressive hematological malignancy etiologically linked to HTLV-I. The clinical subtype classification, age, performance status, serum calcium and LDH levels are major prognostic factors of ATL, but these criteria and factors do not always correlate with prognosis. CD45 is expressed on cells of the hematopoietic system, and plays a pivotal role in antigen-stimulated proliferation of T-lymphocytes. CD45RO is a very light weight isoform of CD45 expressed on activated T-cells. Recent studies have shown that peripheral lymphocytes show two patterns of CD45RO expression in HTLV-I infected individuals which appears to correlate with their clinical outcome. The acute type ATL patients have pattern A with CD45RO+ lymphocytes with intermediate expression (CD45ROint cells), and show a better prognosis than those who do not have any CD45ROint cells. Further studies demonstrated that CD45ROint cells were not infected with HTLV-I, and as a result we suggest that CD45RO expression be considered a marker of host immunity in acute type ATL clinical course, in contrast to the levels of WBC or LDH which are regarded as tumor markers and indicators of tumor mass.

Adult↗

[Evaluation of nasal obstruction with acoustic rhinometry: a simulated study with a nasal model].

The measurement of nasal resistance is important for understanding the pathophysiology of nasal obstruction. However, it is difficult to define the normal range of nasal resistance because of various physiological factors. Several authors have reported that nasal resistance is not correlated with the sensation of nasal obstruction. On the other hand, acoustic rhinometry was introduced by Hilberg et. al. (1989) to determine the geometry of the nasal cavity. The method based on sound reflection analysis provides an estimate of the cross-sectinal area of the nasal cavity as a function of the distance from the nostril. Recently, the measurement by acoustic rhinometry is becoming popular also in our country. However, the assessment by acoustic rhinometry may be different from that by measuring nasal resistance because the cross-sectional area is measured without studying the air flow. The aim of this study was to investigate the benefit of acoustic rhinometry using a nasal model. First, 4 pieces of nasal model LM005 (KOKEN, Co., Japan) made of silicone were coated with resinous putty. Then, the changes in the area-distance curve were measured with an acoustic rhinometer RHIN 2100 (SRE, Co., Denmark) in which this putty was scraped off gradually from anterior to posterior. In the next study, the quality of coated putty was increased at three points of the nasal area: anterior part, middle part, and posterior part. Thereafter the changes in the area-distance curve were observed in the same way. As a result, neither a decrease or an increase in the putty changed the area-distance curve at the posterior part. Therefore, it is suitable that the degree of the changing of nasal mucosa is defined as the change in the nasal volume between the top the I-notch and the end of the C-notch. In conclusion, acoustic rhinometry is useful to investigate nasal obstruction, especially the change in the nasal mucosa. Therefore, further clinical study is required for the different purpose of measuring nasal resistance.

Airway Resistance↗

[An autopsy case of sudden death caused by untreated sepsis after complete remission of acute promyelocytic leukemia].

The patient was 63 year-old man. He had been diagnosed as acute promyelocytic leukemia (APL) and treated until 4 month before his death with complete remission. The patient suddenly died 9 days after he complained of occipital headache. Autopsy and histopathologic findings were as follows: the left pleura was thick and calcificated with abscess, compatible with the findings of old tuberculosis complicated with bacterial infection. Furthermore, polynuclear leukocytes and gram-positive micro-organisms were accumulated in the lungs, and pyogenic meningitis, pyonephritis, splenitis were also found. Bacteologically, Streptococcus pneumoniae was detected from cadaver's blood and cerebrospinal fluid. Therefore, we concluded that the patient was died of septic shock caused by systemic infection of Streptococcus pneumoniae. The mortality of septic shock is high and in some patients, causative organisms may not be isolated. In the present case, although the original inflammation was left pleuritis due to Streptococcus pneumoniae, correct clinical diagnosis was not made before death as the patient had lacked any complaints except for occipital headache. This case revealed that the cause of sudden death was sepsis induced by Streptococcus pneumoniae instead of a relapse of APL. This case also illustrated the importance of reviewing the previous history of a patient and doing postmortem bacteologic examination in a case of suspected sepsis.

Cause of Death↗

Expression of the 150-kd oxygen-regulated protein in human breast cancer.

Tumor cells subjected to environmental stress, such as oxygen deprivation followed by reoxygenation, redirect biosynthetic pathways to express oxygen-regulated proteins (ORPs) and heat-shock proteins (HSPs). The 150-kd oxygen-regulated protein (ORP150) is a novel endoplasmic reticulum-associated polypeptide in the HSP70 family. In view of links between expression of HSPs/ORPs and tumor properties, especially tumor invasiveness and resistance to therapeutic regimens, expression of ORP150 in human breast cancers was examined. Western and Northern blotting demonstrated elevated expression of ORP150 in breast cancer, regardless of estrogen receptor status, compared with normal breast tissue. Immunohistochemical and in situ hybridization techniques revealed that infiltrating cancer cells in the stroma expressed ORP150 more strongly than large nests of cancer cells. Furthermore, pancreatic and thyroid carcinomas also displayed greater ORP150 expression. These results suggest that ORP150 is up-regulated in tumors and, in breast tumors, may be associated with tumor invasiveness.

Adenocarcinoma, Mucinous↗

Genetic analysis of non-insulin-dependent diabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese NIDDM. We performed a genome wide scan in F2 progenies obtained by crossing OLETF rats with two control strains, Long-Evans Tokushima Otsuka (LETO) and Fisher-344(F-344) rats. Since diabetes develops only in male progenies, we used only male F2 rats for the linkage studies.Highly significant linkage was observed between the phenotype, postprandial hyperglycemia and P-450ald locus on chromosome 1 and D7Mit 11 locus on chromosome 7. In addition, suggestive linkage was found between fasting glucose level and body weight and these two loci. Four other regions (D1Mit12, D2Mit11, D5Mgh14, and D17Arb1) on chromosome 1, 2, 5, and 17 were detected to influence body weight, fasting glucose level or postprandial hyperglycemia independently. We concluded that non-insulin-dependent diabetes mellitus(NIDDM) in OLETF rats is regulated by multiple genes which affect fasting, postprandial hyperglycemia, and obesity differently.

Animals↗

Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation.

BACKGROUND: Platelets play pivotal roles in coronary thrombosis, and antiplatelet therapies are widely used for coronary artery disease (CAD). However, the effects of genetic variation in platelets on CAD are poorly understood. We have assessed the association between CAD and polymorphisms in a platelet receptor for von Willebrand factor, the glycoprotein (GP) Ib/IX complex, which mediates shear stress-dependent platelet activation. METHODS AND RESULTS: Genotypes of the alpha-chain of the receptor (GP Ib alpha, 145Thr/Met) were determined in 91 patients with myocardial infarction (MI) or angina pectoris whose lesions were confirmed by coronary angiography as well as in 105 individuals from the general population with no history of angina or other heart diseases and normal resting ECGs. There was no homozygote for Met/Met in either the control or patient groups. The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group. However, the frequency of T/M was significantly higher in patients aged < or = 60 years (31.8%) than in control subjects aged < or = 60 years (16.0%; P<.05, odds ratio=2.5). An association was also demonstrated between CAD and the other polymorphism of GP Ib alpha, a variable number of tandem repeats of a 13-amino acid sequence, which is known to be linked to the 145Thr/Met polymorphism. There was an association between the frequency of the T/M genotype and the angiographic severity of CAD: 11.1% for Gensini score < 40 versus 50.0% for Gensini score > or = 40 (P=.0015). There was no difference in the distribution of GP Ib alpha genotypes between patients with MI and those with angina pectoris. CONCLUSIONS: This study suggests that the presence of the Met allele in GP Ib alpha is a risk factor for the prevalence and severity of CAD in individuals aged < or = 60 years. The results need to be confirmed in a large-scale study of incident case subjects and matching control subjects.

Adult↗