Biomedical subjects

Kenji Suzuki

Publications and source records attributed to Kenji Suzuki.

At least 127 records · Page 7Linked to original sources

PubMed2003

Association between lifestyle and white blood cell count: a study of Japanese male office workers.

METHODS: We assessed the association of lifestyle factors with white blood cell (WBC) count in 3681 Japanese male office workers aged 35-59 years. RESULTS: The WBC count differed significantly across lifestyle factors (overall obesity, alcohol consumption, cigarette smoking, eating breakfast, nutritional balance, physical exercise and hours of work). From multiple linear regression analyses, overall obesity, alcohol intake, cigarette smoking, nutritional balance and hours of work remained as statistically significant factors associated with WBC count. The WBC count increment showed a positive dose-response relationship with poor lifestyle factors regarding overall obesity, cigarette smoking and nutritional balance. On the other hand, the WBC count increment showed a negative dose-response relationship with alcohol intake and hours of work. CONCLUSION: These data indicate that lifestyle factors may exert an important effect on WBC count.

Adult↗

PubMed2003

Topical ofloxacin for chronic suppurative otitis media and acute exacerbation of chronic otitis media: optimum duration of treatment.

OBJECTIVE: To assess the optimum duration of topical ofloxacin therapy for chronic otitis media and to compare the response between patients with chronic suppurative otitis media (CSOM) and acute exacerbation of chronic otitis media (AE). STUDY DESIGN: Prospective observational study. SETTING: Five university hospitals and 30 affiliated institutions. PATIENTS: A total of 294 patients who presented to the participating institutions with CSOM were enrolled. Among them, 268 patients were evaluable for safety and 237 were evaluable for efficacy (64 with CSOM and 173 with AE . INTERVENTION: Ofloxacin otic solution was administered for as long as 4 weeks. MAIN OUTCOME MEASURES: Clinical and bacteriologic assessment was done weekly during the treatment period. The clinical response was assessed on the basis of the symptom scores. RESULTS: There were no differences between CSOM and AE patients with respect to sex, age, and severity. The most common bacterial isolate from middle ear discharge was Staphylococcus aureus. The clinical response rates in patients with CSOM and AE were 39.1% and 61.3% after 2 weeks of treatment and 57.8% and 75.1% after 4 weeks, respectively, and the bacterial eradication rate was 91.0% at 2 weeks and 94.6% at 4 weeks. Detection of new fungal infection did not increase as the duration of therapy was prolonged. No serious adverse events were reported. CONCLUSIONS: The duration of treatment was shorter and the clinical response was higher in AE patients than in CSOM patients. The standard topical ofloxacin regimen for chronic otitis media should consist of a 2-week course from the aspect of bacteriologic efficacy, although patients showing insufficient symptomatic improvement after 2 weeks may benefit from another 1 or 2 weeks of therapy. Administration of this drug for as long as 4 weeks can increase the clinical efficacy without causing safety problems.

Acute Disease↗

PubMed2003

Elective laparoscopy for small bowel obstruction.

We performed elective laparoscopic adhesiolysis in 21 patients with small bowel obstruction. The procedure was completely laparoscopic or laparoscopy assisted in 17 patients, but 4 patients required full laparotomy due to internal hernia in 2, perforation of the small bowel associated with dense adhesions in 1, and carcinoma of the cecum in 1. In patients with a laparoscopic or laparoscopy-assisted procedure, the mean operating time, mean time until the return of bowel function, and mean postoperative stay were 94 minutes, 3.3 days, and 9.9 days, respectively. During follow-up for 14 to 44 months, 3 patients developed recurrent obstruction, 1 patient suffered from catheter-induced thrombosis, and 1 patient died from lung cancer. Elective laparoscopy can be performed safely and effectively in selected patients with intermittent small bowel obstruction.

Adult↗

PubMed2003

IFN-inducible protein-10 has a differential role in podocyte during Thy 1.1 glomerulonephritis.

IFN-inducible protein-10 (IP-10/CXCL10) is a potent chemoattractant for activated T lymphocytes and was recently reported to have several additional biologic activities. In this study, the expression and the function in normal glomeruli and in Thy1.1 glomerulonephritis (GN) were investigated. The expression of IP-10 was detected in normal rat glomeruli mainly in the podocyte. The expression of IP-10 was also detected on the cultured podocyte. The IP-10 expression was elevated at the early phase of Thy1.1 GN. The double staining immunofluorescence study clearly demonstrated that the elevated expression of IP-10 was mostly detected in the podocyte and very partly in mesangial area. A receptor for IP-10, CXCR3, showed similar expression patterns to that of IP-10. Expressions of neither of IP-10 nor of CXCR3 were detected on the inflammatory cells. For elucidating the role of IP-10, the blocking study was carried out with monoclonal anti-IP-10 antibody. The monoclonal anti-IP-10 antibody treatment decreased the expression of IP-10 and podocyte-associated proteins such as nephrin and podocin that are reported to be essential for maintaining the podocyte function (IP-10, 53.0% to control; nephrin, 43.5%; podocin, 60.4%). The findings indicated that the anti-IP-10 treatment disturbed the podocyte function. The anti-IP-10 treatment given to the rats with Thy1.1 nephritis exacerbated proteinuria, mesangiolysis, and matrix expansion. Collectively, the findings indicated that IP-10 plays a role in maintaining the podocyte function. Also, the findings suggested that anti-IP-10 treatment exacerbated the glomerular alterations in Thy1.1 GN by disturbing the podocyte function.

Animals↗

PubMed2003

Clustering of cardiovascular risk factors and risk of development of hypertension in Japanese male office workers.

BACKGROUND: Obesity, hypercholesterolaemia, low high-density lipoprotein cholesterol levels, hypertriglyceridaemia, high fasting plasma glucose levels, hyperuricaemia and increased white blood cell count levels are all positively associated with the risk of hypertension, but the effect of the clustering of these risk factors on the risk for development of hypertension remains unclear. DESIGN: Longitudinal study at a work site in Osaka, Japan. METHODS: We examined 3784 Japanese male office workers aged 30 to 59 years who were hypertension-free [systolic blood pressure (SBP) < 140 mmHg, diastolic blood pressure (DBP) < 90 mmHg, no medication for hypertension, and no past history of hypertension]. Blood pressures were measured at annual health examinations from May 1996 to May 2001. RESULTS: After controlling for potential predictors of hypertension, the relative risk of hypertension (SBP>/=140 mmHg, DBP>/=90 mmHg, or both or prescription of antihypertensive medication) compared with the presence of no risk factors was 1.41 (95% CI, 1.21 to 1.64), 1.64 (95% CI, 1.38 to 1.96), 1.93 (95% CI, 1.56 to 2.39), 2.01 (95% CI, 1.51 to 2.68) and 3.34 (95% CI, 2.07 to 5.38) (P value for trend < 0.001) for respective risk factors of 1, 2, 3, 4 and >/=5. Even after the subjects were stratified according to blood pressure, the clustering of risk factors was associated with an increased risk of hypertension for subjects in all three categories of normotension: low-normal, normal, and high-normal. CONCLUSIONS: Clustering of cardiovascular risk factors associated with hypertension precedes an increase in the risk of hypertension in Japanese men.

Adult↗

PubMed2003

Massive training artificial neural network (MTANN) for reduction of false positives in computerized detection of lung nodules in low-dose computed tomography.

In this study, we investigated a pattern-recognition technique based on an artificial neural network (ANN), which is called a massive training artificial neural network (MTANN), for reduction of false positives in computerized detection of lung nodules in low-dose computed tomography (CT) images. The MTANN consists of a modified multilayer ANN, which is capable of operating on image data directly. The MTANN is trained by use of a large number of subregions extracted from input images together with the teacher images containing the distribution for the "likelihood of being a nodule." The output image is obtained by scanning an input image with the MTANN. The distinction between a nodule and a non-nodule is made by use of a score which is defined from the output image of the trained MTANN. In order to eliminate various types of non-nodules, we extended the capability of a single MTANN, and developed a multiple MTANN (Multi-MTANN). The Multi-MTANN consists of plural MTANNs that are arranged in parallel. Each MTANN is trained by using the same nodules, but with a different type of non-nodule. Each MTANN acts as an expert for a specific type of non-nodule, e.g., five different MTANNs were trained to distinguish nodules from various-sized vessels; four other MTANNs were applied to eliminate some other opacities. The outputs of the MTANNs were combined by using the logical AND operation such that each of the trained MTANNs eliminated none of the nodules, but removed the specific type of non-nodule with which the MTANN was trained, and thus removed various types of non-nodules. The Multi-MTANN consisting of nine MTANNs was trained with 10 typical nodules and 10 non-nodules representing each of nine different non-nodule types (90 training non-nodules overall) in a training set. The trained Multi-MTANN was applied to the reduction of false positives reported by our current computerized scheme for lung nodule detection based on a database of 63 low-dose CT scans (1765 sections), which contained 71 confirmed nodules including 66 biopsy-confirmed primary cancers, from a lung cancer screening program. The Multi-MTANN was applied to 58 true positives (nodules from 54 patients) and 1726 false positives (non-nodules) reported by our current scheme in a validation test; these were different from the training set. The results indicated that 83% (1424/1726) of non-nodules were removed with a reduction of one true positive (nodule), i.e., a classification sensitivity of 98.3% (57 of 58 nodules). By using the Multi-MTANN, the false-positive rate of our current scheme was improved from 0.98 to 0.18 false positives per section (from 27.4 to 4.8 per patient) at an overall sensitivity of 80.3% (57/71).

Algorithms↗

PubMed2003

Quantitative computerized analysis of diffuse lung disease in high-resolution computed tomography.

An automated computerized scheme has been developed for the detection and characterization of diffuse lung diseases on high-resolution computed tomography (HRCT) images. Our database consisted of 315 HRCT images selected from 105 patients, which included normal and abnormal slices related to six different patterns, i.e., ground-glass opacities, reticular and linear opacities, nodular opacities, honeycombing, emphysematous change, and consolidation. The areas that included specific diffuse patterns in 315 HRCT images were marked by three radiologists independently on the CRT monitor in the same manner as they commonly describe in their radiologic reports. The areas with a specific pattern, which three radiologists marked independently and consistently as the same patterns, were used as "gold standard" for specific abnormal opacities in this study. The lungs were first segmented from the background in each slice by use of a morphological filter and a thresholding technique, and then divided into many contiguous regions of interest (ROIs) with a 32x32 matrix. Six physical measures which were determined in each ROI included the mean and the standard deviation of the CT value, air density components, nodular components, line components, and multilocular components. Artificial neural networks (ANNs) were employed for distinguishing between seven different patterns which included normals and six patterns associated with diffuse lung disease. The sensitivity of this computerized method for a detection of the six abnormal patterns in each ROI was 99.2% (122/123) for ground-glass opacities, 100% (15/15) for reticular and linear opacities, 88.0% (132/150) for nodular opacities, 100% (98/98) for honeycombing, 95.8% (369/385) for emphysematous change, and 100% (43/43) for consolidation. The specificity in detecting a normal ROI was 88.1% (940/1067). This computerized method may be useful in assisting radiologists in their assessment of diffuse lung disease in HRCT images.

Algorithms↗

PubMed2003

Alcohol consumption and risk for development of impaired fasting glucose or type 2 diabetes in middle-aged Japanese men.

OBJECTIVE: To investigate the association between alcohol consumption and risk for development of diabetes. RESEARCH DESIGN AND METHODS: We examined 2,953 Japanese male office workers aged 35-59 years who did not have impaired fasting glucose (IFG) (a fasting plasma glucose concentration of 6.1-6.9 mmol/l), type 2 diabetes (a fasting plasma glucose concentration of > or =7.0 mmol/l or receipt of hypoglycemic medication), medication for hypertension, or a history of cardiovascular disease. Fasting plasma glucose concentrations were measured at periodic annual health examinations from May 1994 through May 2001. RESULTS: There was a U-shaped association between alcohol consumption and the incidence of IFG or type 2 diabetes during 7 years of follow-up, with the lowest incidence at alcohol intake of 23.0-45.9 g ethanol/day. After controlling for age, family history of diabetes, BMI, cigarette smoking, and physical activity, the relative risk for development of IFG or type 2 diabetes compared with alcohol consumption of 23.0-45.9 g ethanol/day was 1.51 (95% CI, 1.07-2.13), 1.31 (95% CI, 0.93-1.84), 1.18 (95% CI, 0.87-1.61), and 1.43 (95% CI, 1.01-2.02) with alcohol consumption of 0, 0.1-22.9, 46.0-68.9, and > or =69.0 g ethanol/day, respectively (P for quadratic trend = 0.016). Analyses by presence or absence of a risk factor revealed that a U-shaped association was more evident in older men, men without a family history of diabetes, and nonsmokers. CONCLUSIONS: These results indicate that moderate alcohol consumption among apparently healthy Japanese men is associated with reduced risk for development of IFG or type 2 diabetes.

Adult↗

PubMed2003

Multiple risk factor clustering and risk of hypertension in Japanese male office workers.

Major risk factors associated with hypertension (a family history of hypertension, obesity, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and increased white blood cell counts) were assessed in 5275 Japanese male office workers aged 23-59 years. After controlling for potential risk factors of hypertension, the odds ratio of hypertension compared with the absence of risk factors was 1.91, 2.65, 3.88, 6.54, and 8.18 for the presence of 1, 2, 3, 4, and > or = 5 risk factors, respectively (P for trend < 0.001). Systolic and diastolic blood pressure levels also increased in a dose-dependent manner as the number of risk factors increased. Among men not taking antihypertensive medication, the adjusted mean differences in systolic and diastolic blood pressures (mmHg) were 11.2 and 9.2 between men with the presence of > or = 5 risk factors and men without risk factors, respectively. These results indicate that the accumulation of risk factors is highly associated with the increased risk of hypertension in Japanese men.

Adult↗

PubMed2003

[A questionnaire survey on the theory of postoperative infection prophylaxis in otorhinolaryngology].

A questionnaire survey on postoperative infection prophylaxis was conducted to achieve the consensus on the perioperative antimicrobial use among otolaryngologists in Japan during the period of time from April to July 2000. Fifty-two out of 84 otolaryngologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Pseudomonas aeruginosa and Bacteroides fragilis group; Use an AMP agent that achieves a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. Newer agents should be considered as therapeutics for postoperative infections. Therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations is cefazolin (CEZ), followed by cefotiam (CTM) and piperacillin (PIPC), in this order. For clean-contaminated operations, the most commonly used agent is CEZ, followed by flomoxef (FMOX) and CTM.

Antibiotic Prophylaxis↗

PubMed2003

Posture of patients with sleep apnea during sleep.

The relationship between sleep apnea syndrome (SAS) and posture during sleep has been noted and the beneficial effect of an optimal posture on sleep apnea has been empirically indicated. We investigated this effect in a group of subjects that included obese patients and found that the apnea-hypopnea index (AHI) may be normalized in the lateral position, even among patients severely affected with apnea. Among those with intermediate or lower AHI values sleeping in a lateral position markedly improved the symptoms, with AHI even approaching the normal range in many patients. A tendency was noted for AHI to rise regardless of posture but in proportion to the increase in body mass index (BMI). In other words, the improvement due to changes in posture became increasingly insignificant with increase in BMI.

Adult↗

PubMed2003

[Evaluation of the 123I-IMP Patlak plot method using the pulmonary differential curve as an input function: a comparison with cerebral blood flow (CBF) determined by the noninvasive micro-sphere (NIMS) method].

We explored the possibility of applying the Patlak plot method to clinical practice as a simple non-invasive quantitative method of measuring cerebral blood flow using N-isopropyl-4-[123I]iodoamphetamine (123I-IMP). On the assumption that after temporarily accumulating in the lungs, all the administered 123I-IMP is eliminated by the pulmonary arterial flow for systemic diffusion, we collected dynamic data by setting an area ranging from the brain to the whole lung field within the field of the camera. The lung clearance curve L(t) was differentiated and divided by cardiac output. It was then converted a positive number by multiplying it of--1 to determine the volume of 123I-IMP tracer diffused in arterial blood per unit of time. The calculated concentration was defined as the arterial time activity curve A(t). A Patlak plot analysis was conducted between A(t) and the brain time activity curve B(t) to determine K1 (total cerebral blood flow [tCBF], ml/min) and Vn (nonspecific initial distribution volume, ml). The total volume of tracer diffused in the central cardiovascular system within a given (T) was also obtainer from the volume of tracer remaining in the lungs [Lpeak--L(T)], and by reporting this calculation over time, an accumulation curve was produced. By differentiating the obtained accumulation curve, we were able to estimate the volume of tracer diffused in the central cardiovascular system per unit of time. With this value used as the input function index I(t), a Patlak plot analysis was conducted to determine the unidirection influx index ki, which was then multiplied by 100 to obtain the brain perfusion index (IMP-BPI). The noninvasive micro-sphere method was performed concurrently on 16 patients with cerebrovascular and/or neurological disorders to obtain mean cerebral blood flow (mCBF). Correlations between K1 and between IMP-BPI and mCBF were then determined and compared. Both K1 and IMP-BPI obtained from ki were found to correlate highly with mCBF, r = 0.759 (y = 0.032x + 20.1) and r = 0.833 (y = 2.73x + 0.10) respectively, with a better result from IMP-BPI. These results indicate that the 123I-IMP Patlak plot method with a wide-field gamma camera is clinically applicable as a simpler noninvasive technique for measuring cerebral blood flow even when a simple input function is used.

Adolescent↗

PubMed2003

[Japanese national survey of adolescent drinking behavior: comparison between 1996 and 2000 surveys].

This report shows Japanese adolescent drinking behavior from the national surveys conducted in 1996 and 2000. We randomly selected 120 junior high schools and 100 senior high schools nationwide. We requested the cooperation of the principals of these schools and sent questionnaires to each school. Students answered anonymously the questionnaires during school time, and sealed in envelopes by themselves; then teachers collected the envelopes. The questionnaire focused on adolescent drinking behavior. Valid responses numbered 42,798 (1996) and 47,246 (2000) from the junior high schools and 73,016 (1996) and 59,051 (2000) from the senior high schools. The number of students surveyed represented about 1% of all Japanese junior high school students, and about 2% of all senior high school students. This report covers only students who gave answers on both drinking frequency and drinking quantity. It compares adolescent drinking behavior between the 1996 and 2000 surveys, such as drinking frequency, drinking quantities, drinking occasions, methods of obtaining alcohol, kinds of alcohol drunk, alcohol-related problems, opinions on the law that prohibits minors under 20 years of age from drinking alcohol, and distribution of drinking status of the subjects by the Quantity-Frequency Scale (QF scale). In a comparison of adolescent drinking behavior between the 1996 survey and 2000 survey, non-drinkers among junior high school students increased from 45% to 55%, and those among senior high school students increased from 27% to 33%. On the other hand, ratios of female students in both junior and senior high schools who drank 1 or more times per week were higher in the 2000 survey than in the 1996 survey. Comparison of the 1996 survey and 2000 survey did not indicate that Japanese adolescent drinking has increased or decreased.

Adolescent↗

PubMed2003

Correlation of PP and PR intervals in premature low birth weight infants.

We examined the developmental change by which autonomic neural activity associated respiration modulates spontaneous firing rate of sinus (SA) node and atrioventricular (AV) conduction in premature infants born with low birth weight (LBWI). The purpose of this study was to clarify whether variation of PR is correlated with that of PP or those are independent in LBWI with immature autonomic nervous system. We investigated, therefore, whether there are spontaneous functional differences in the innervation of SA and AV nodes. Further, we evaluated the maturation of autonomic nervous system progressing in the period, on the day of birth (Day 0) to approximately one month after the birth (Month 1). This study was performed in thirteen LBWI during deep sleep. EEG, EOG, ECG, respiratory waves were digitized on line, spontaneous firing cycle of SA node (PP), and AV nodal conduction time (PR) that were recorded on Day 0 and Month 1. Then, the data were analyzed as follows: 1) correlations among the means and standard deviations (SD) of PP, PR and RR, 2) variance evaluation of PP and PR intervals by Lorenz plot analysis method, 3) correlation analysis among PP, PR and RR intervals by linear regression method and 4) frequency analysis for PP and PR intervals by high-speed Fourier transform method (FFT) and determination of frequency density. The PP interval decreased as growing in the period. Contrary PR interval increased. In LBWI, the automatic nervous activities including parasympathetic nerve activity for spontaneous firing cycle of SA node and ventricular excitation cycle on Month 1 were higher than Day 0. It was assumed that the vagal nerve activity for the AV conduction was enhanced. However, there was no significant change in linear regression slope for the spontaneous firing cycle of SA node and the AV conduction time. Postnatal LF/HF changes for PP and PR obtained by frequency analysis, were opposite. Therefore, it was suggested that the maturity of autonomic nervous system progresses in the period, Day 0 to approximately Month 1, but the variations in PP and PR are independent each other.

Atrioventricular Node↗

PubMed2003

[Brief intervention for smoking, problem drinking and drug abuse by high school students].

Adolescent smoking, drinking and illegal drug abuse (drug-related problems) in Japan were treated as a legal model in the second prevention area. This study showed the necessity and usefulness of early intervention concerning adolescent drug-related problems as adolescent mental health problems. First, school nurses were asked if they were consulted about drug-related problems by students. Many school nurses in junior and senior high schools were consulted about drug-related problems by students, and they emphasized the need for counseling systems for drug-related problems by professionals. The second part of the study involved brief interventions by the authors in high school students with a high risk of drug-related problems. The authors went to three high schools and conducted brief interventions on students who had drug-related problems and sought advice. We prepared several screening tests for assessment of drug-related problems, such as the Fagerström Test for Nicotine Dependence (FTND). Adolescent Alcohol Involvement Scale (AAIS). Quantity-Frequency Scale (QF Scale). Core Alcohol Use Disorders Identification Test (Core AUDIT), CAGE and Drug Abuse Screening Test-20 (DAST-20). In the brief interventions, the authors assessed drug-related problems of students using these scales and advised them how to revolve such problems two or three times. Twenty-two students accepted brief interventions. All of them smoked, 62% of them showed problem drinking and 33% illegal drug use. At 6 months after the brief interventions, 16 out of 21 students reported their drug-related problems. Nineteen percent of them had reduced smoking, 67% of them decreased drinking and one half of them decreased their use of illegal drugs. Results of this study revealed the necessity and the usefulness of the brief intervention for high school students with drug-related problems.

Adolescent↗

PubMed2003

Adolescent smoking behavior in Japan, 1996.

We conducted second nationwide survey on smoking behavior among Japanese high school students. The survey was a cross-sectional sampling survey. The survey's targets were junior and senior high schools throughout Japan. Sample schools were selected by stratified cluster sampling. Self-administered anonymous questionnaires were sent to sample schools for all students to fill out. 65.6% of the junior high schools and 67.0% of the senior high schools were responded to this survey. A total of 117,325 students responded and 115,814 questionnaires were subjected to analysis. 7.5% of boys and 3.8% of girls in the 1st grade of junior high school were classified as current smokers, compared with 36.9% of boys and 15.6% of girls in 3rd grade of senior high school. Less than 1% of boys and girls in the 1st grade of junior high school were classified as daily smokers, this figure increased markedly by the 3rd grade of senior high school to reach 25.4% of boys and 7.1% of girls. Of students in the 3rd grade of senior high school, 21.2% of boys and 9.9% of girls had tried smoking before 13 year of age. Cigarette consumption also increased with age, although the proportion of those smoking 20 or more cigarettes per day did not. The major source for cigarettes among current smokers was vending machines. This survey revealed that smoking prevalence among Japanese high school students has already reached quite high level. Comprehensive energetic measures for control minor smoking are necessary in Japan.

Adolescent↗

PubMed2002

The crystal structure of N(1)-[2-(2-amino-ethylamino)-ethyl]-ethane-1,2-diamine (polyamines) binding to the minor groove of d(CGCGCG)(2), hexamer at room temperature.

The crystal structure of a left-handed Z-DNA hexamer, d(CG)(3) in complex with a synthetic polyamine, N(1)-[2-(2-amino-ethylamino)-ethyl]-ethane-1,2-diamine, NH(3)(+)-(CH(2))(2)-NH(2)(+)-(CH(2))(2)-NH(2)(+)-(CH(2))(2)-NH(3)(+) [PA(222)], has been determined by the X-ray diffraction method at 1.0 A resolution. In an orthorhombic crystal, the d(CG)(3) duplex binds two PA(222) molecules, and this synthetic polyamine exhibits dual conformational properties. One of the two PA(222) molecules resides on the floor of the minor groove of a Z-DNA duplex and imino groups bridge the two phosphate chains across a double helix, while the terminal amino groups link the oxygen atoms O2 of four cytosine bases. This PA(222) molecule makes a U-turn like a fishhook at one of its ends to provide a micro-environmental network previously unseen in complexes of DNA with polyamines. The width of the minor groove does not become considerably greater with the looped end of the polyamine, indicating conformational rigidity of the Z-DNA backbone imposed by the high stacking energy of the GC base pairs. While polyamine binding to the minor groove has been postulated by theoretical studies for stabilizing the Z-DNA double helical conformation, the finding in the crystal of the looped polyamine chain binding the minor groove of Z-DNA is observed for the first time from the data collected at 10 degrees C (so-called room temperature data). Another PA(222) molecule binds on the convex outer surface of the major groove of the Z-DNA duplex and links three d(CG)(3) duplexes which are symmetrically related to each other. The structure of this PA(222) presents the previously reported zig-zag type conformation [Egli et al., Biochemistry 30 (1991) 11388-11402]. Comparison of this structure with other polyamine-DNA cocrystals reveals structural themes and differences that may relate to the length of the polyamine.

Binding Sites↗

PubMed2002

Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor.

Brain-derived neurotrophic factor (BDNF) binds to and activates the TrkB tyrosine kinase receptor to regulate cell differentiation, survival, and neural plasticity in the nervous system. However, the identities of the downstream signaling proteins involved in this process remain unclear. Using a yeast two-hybrid screen with the intracellular domain (ICD-TrkB) of the TrkB BDNF receptor, we identified the Nck2 adaptor protein as a novel interaction partner of the active form of TrkB. Additionally, we identified three tyrosines in ICD-TrkB (Y694, Y695, and Y771) that are crucial for this interaction. Similar results were obtained for Nck1, an Nck2 homolog. We also found that TrkB could be co-precipitated with GST-Nck2 recombinant protein or anti-Nck antibody in BDNF-activated cortical neurons. These results suggest that BDNF stimulation promotes interaction of Ncks with TrkB in cortical neurons.

Amino Acid Sequence↗