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Biomedical subjects

K Togashi

Publications and source records attributed to K Togashi.

At least 19 recordsLinked to original sources

Involvement of apoptosis in syncytial cell death induced by canine distemper virus.

The Yanaka strain, a field isolate of Canine distemper virus (CDV), caused extensive syncytial cytopathic effects (CPEs) followed by cell death in vitro. Syncytium formation is an important aspect of CDV pathogenicity, but the mechanism of the fusion-induced cell death is still not understood. In this study, the involvement of apoptosis in the CDV-induced CPE was investigated. We also examined apoptosis in cells infected with a persistent strain of CDV, the Yanaka-BP strain derived from the Yanaka strain, because this strain does not cause obvious CPE. DNA laddering together with Terminal transferase dUTP nick endlabeling (TUNEL) assay indicated that the Yanaka strain infection, but not the Yanaka-BP infection induced apoptosis. In addition, flow cytometric analysis similarly indicated that the Yanaka-BP strain induced apoptosis significantly less frequently than the Yanaka strain did. Thus, absence of apoptosis may be implicated in the CPE and establishment of persistent CDV infection.

Animals↗

Sex differences in the relationships of abdominal fat to cardiovascular disease risk among normal-weight white subjects.

The objectives of this study are to investigate the relationships between abdominal fat and risk factors for cardiovascular disease (CVD) among normal-weight (NW) white subjects and to determine how these relationships differ by sex. NW adults (177 males and 258 females) and overweight adults (133 males and 111 females) from the Québec Family Study and the HERITAGE Family Study were retained for this study. Risk factors included systolic and diastolic blood pressures, low-density lipoprotein and high-density lipoprotein cholesterols, triglycerides, and fasting glucose. Only in NW female adults, abdominal visceral fat (AVF) area assessed by computed tomography was significantly correlated with all risk factors, except for fasting glucose, even after age, study cohort, and fat mass were taken into account. NW female subjects with at least one risk factor had a significantly higher AVF than those without risk factors, although the difference was small. Thus, only NW female adults with more AVF tended to have a more adverse CVD risk factor profile.

Abdomen↗

Efficiency of different selection criteria for persistency and lactation milk yield.

A conversion formula was developed to convert the genetic covariance matrices of daily yields and of random regression coefficients between 305-d and 335-d production periods under a random regression test day model. Five selection criteria were compared in terms of genetic improvement in persistency and lactation milk: 1) lactation estimated breeding value (EBVL), 2) P6 = 279Sigma(i=65) (D280 - Di), 3) ratio of daily estimated breeding value (EBV)(r280/65 = D280/D65), 4) ratio of partial lactation EBV (P280/65 = D66 approximately 28/D5 approximately 65), and 5) differential daily EBV (d65-280 = D65 - D280), where Di refers to EBV at days in milk (DIM) i. Fundamental differences among these 5 selection criteria were interpreted conceptually with a graph. Persistency, defined as k = (delta G65 - delta G280)/215, was the average daily rate of decline in selection gain from DIM 65 to 280, which is free from the effect of lactation milk on the rate of decline. Parameter k provides an objective measure of persistency, which increases when k < 0 and decreases when k > 0. Of the 5 selection criteria compared, d65-280 and P6 achieved greater persistency at the expense of genetic gain in lactation milk, whereas selection based on EBVL achieved the highest response in lactation milk, but was coupled with greatest decline in persistency. Selection on P280/65 or r280/65 improved both lactation milk and persistency and, thus, is recommended for simultaneous improvement of these 2 economically important traits. Further study of the relative economic values of persistency and lactation milk in order to combine both traits into an index for selection decision is warranted.

Animals↗

Development of an optimal index to improve lactation yield and persistency with the least selection intensity.

It is important to have improvement in both lactation milk yield and persistency. Modification of the lactation curve requires severe restrictions on selection criteria designed to simultaneously improve both milk yield and persistency. As a result, manipulating the lactation curve for improved persistency requires higher selection intensity than unrestricted selection based on 305-d estimated breeding value (EBV). Our study showed that for a given restriction imposed on both milk EBV and persistency, it is possible to derive different indexes to achieve this selection constraint with different degrees of selection intensity. Of the class of indexes that meets the same restriction, it is preferable to choose the index that requires the least selection intensity because it is easier to achieve the selection goal with the use of an index that requires a lower selection intensity than a higher selection intensity. An optimal index based on random regression (RR) coefficients was developed to achieve the prespecified stage genetic gains with the lowest selection intensity. A conversion equation was derived to convert the selection index based on RR coefficients to the selection index based on stage EBV with the lowest selection intensity. A numerical example is provided to demonstrate the procedures developed compared with conventional selection based on 305-d milk EBV.

Animals↗

Modifying the lactation curve to improve lactation milk and persistency.

Daily, stage and lactation estimated breeding values (EBV) and the shape of the lactation curve for each cow are controlled by a unique set of random (genetic) regression coefficients under a test day model, thus providing a basis for genetic improvement of these characteristics. Three selection procedures were developed for simultaneous improvement of total lactation milk and persistency: 1) index selection based on daily EBV, 2) index selection based on stage EBV, and 3) index selection based on random regression (RR) coefficients. A numerical example was given to demonstrate the computation of indexes based on stage EBV and based on RR coefficients. A conversion equation was derived to convert between genetic changes in EBV and RR coefficients. Index selection based on daily EBV would require the finding of 305 weighting factors for a lactation period of 305 d, making it impractical to determine the weighting factors on a daily basis. Alternatively, a lactation period was partitioned into a few stages to facilitate the construction of index selection based on stage EBV and index selection based on RR coefficients. These selection procedures make use of the annual genetic gains routinely computed in national genetic evaluations to restrict the genetic gains between different lactation stages to achieve the desired curve. When there is no prior knowledge of annual genetic gains, the proportional restriction of genetic gains between stages may be used. In summary, this study provides a simple means of modifying the lactation curve by manipulating genetic changes in different lactation stages at a pre-specified rate.

Animals↗

[Pneumothorax due to pulmonary metastasis of gingival carcinoma: report of a case].

A 72-year-old woman developed left pneumothorax 14 months after the first operation of a gingival carcinoma. The chest X-ray films and computed tomographic scans on admission revealed left pneumothorax and 2 lesions with a thin-walled cavity in the upper lung field. They seemed to be pulmonary metastasis from a carcinoma of gingiva and one of them ruptured into the pleural cavity. As airleak continued after tube thoracostomy, wedge resections of 2 lesions were performed through thoracotomy. Postoperative histological examination revealed that both of the lesions were moderately differentiated squamous cell carcinoma and they were the same histological findings as the gingival carcinoma excised previously. Pulmonary metastasis from a carcinoma of gingiva is rare, while it may be thought 1% of metastatic lung tumors. And also pulmonary metastasis is unusual cause of pneumothorax, especially without chemotherapy for it. We reported the very rare case of pneumothorax due to pulmonary metastasis from a carcinoma of gingiva.

Aged↗

Flat and depressed lesions of the colon and rectum: Pathogenesis and clinical management.

INTRODUCTION: It is not clear whether flat lesions play a role in the pathogenesis of colorectal carcinoma. Flat lesions are being increasingly recognised with new colonoscopic techniques. MATERIALS AND METHODS: A total of 10,939 consecutive colonoscopies were performed over a 9-year period. After bowel preparation with polyethylene glycol electrolyte lavage solution, high-resolution video colonoscopy and indigocarmine spraying were performed to detect flat lesions. All lesions suggesting neoplastic change were removed by polypectomy or surgery. Cancers invading beyond the submucosal layer were excluded from this analysis. The gross appearance of flat-type lesions was classified as flat elevated type or flat depressed type based on the presence or absence of central depression. RESULTS: A total of 5408 neoplastic lesions were index lesions, including 5035 adenomas and 373 carcinomas (124 with submucosal invasion). The prevalence of flat depressed and flat elevated lesions were 2.8% and 18.1%, respectively. Submucosal invasion rates were 17.1% in the flat depressed, 0.8% in the flat elevated, 1.6% in the sessile, 4.0% in pedunculated lesions and 9.3% in creeping lesions. The submucosal invasion rate in the flat depressed lesions was significantly higher than in any others, except for creeping lesions (P = 0.06). The percentage of flat elevated and flat depressed carcinomas among all carcinomas invading the submucosa was 6.5% and 21.0%, respectively. CONCLUSION: Flat lesions were common during routine colonoscopy. One-quarter of colorectal cancers may be derived from flat lesions. Training in dye spray technique may result in a higher detection rate of flat colonic lesions.

Adenoma↗

[Elucidation of one-lobe intrapulmonary metastasis route of primary lung cancer by means of long-term results].

OBJECTIVE: We hypothesized that the cause of one-lobe intrapulmonary metastasis of primary lung cancer is mainly lymphatic, and investigated by means of the long-term outcome. METHODS: From 1988 to 2000, 860 patients underwent complete resection of primary lung cancer patients in our hospital without neoadjuvant therapy. Patients were classified into 4 groups: group A (n 0 pm 0, n = 573), group B (n 0 pm 1, n = 37), group C (n 1 pm 0-1, n = 122), and group D (n 2 pm 0-1, n = 128). RESULTS: No significant difference was seen between groups in median age, sex ratio, histological cell type, or pathological tumor-size and p-factor. The rates of bi-lobectomy and pneumonectomy were higher in groups C and D than in groups A and B. The 5-year survival rate was 73% for group A, 57% for group B, 43% for group C, and 28% for group D. The 10-year survival rate was 57% for group A, 45% for group B, 20% for group C, and 16% for group D. There was a significant difference (p < 0.0001) between 4 groups in the 5- and 10-year survival rate. CONCLUSION: The hypothesis that the cause of one-lobe intrapulmonary metastasis may be lymphatic was not incompatible with the long-term results.

Adult↗

Oviposition deterrence associated with larval frass of the Japanese pine sawyer, Monochamus alternatus (Coleoptera: Cerambycidae).

To determine the effect of larval frass of Monochamus alternatus on oviposition preference of the female adults, three tests were performed in the laboratory. Individual females were provided with a frass-coated, Pinus densiflora bolt and an untreated bolt simultaneously and were allowed to oviposit for 24 h. They deposited a significantly smaller number of eggs on frass-coated bolts. The females supplied with frass-coated bolts deposited no eggs on them, indicating that the larval frass deterred the females from oviposition. When individual females were provided simultaneously with a pine bolt applied with a methanol extract of larval frass and another bolt applied with methanol alone, they deposited a significantly smaller number of eggs on frass extract-applied bolts for 24 h. These results suggest the presence of a putative oviposition deterrent in larval frass of M. alternatus. Each test was replicated 19-20 times using different females.

Journal Article↗

Is adiposity at normal body weight relevant for cardiovascular disease risk?

OBJECTIVE: To examine the relation between adiposity and risk factors for cardiovascular disease (CVD) in normal weight (NW) individuals. METHODS: Cross-sectional study using the sample of white people, aged from 17 to 60 y from the Québec Family Study and the Heritage Family Study. NW subjects with a body mass index (BMI) between 18.5 and 25 kg/m(2) (181 males and 265 females) and overweight (OW) subjects with a BMI between 25 and 30 kg/m(2) (133 males and 114 females) were retained for this study. NW subjects were divided into quintiles of each adiposity variable, then the quintiles and the OW group were evaluated for the presence of CVD risk factors. Using logistic regression analysis, the odds ratio (OR) for the prevalence of risk factors for each quintile of each adiposity variable and the OW group was estimated relative to the first quintile in NW subjects. Mean values of adiposity variables were compared between the subjects with and without risk factors. In these analyses, age and study cohort effects were taken into account. MEASUREMENTS: Percentage body fat (%fat) and fat mass (FM) measured by underwater weighing were available as adiposity variables. Risk factors included systolic and diastolic blood pressure, LDL and HDL cholesterol, triglycerides and fasting glucose. RESULTS: Wide ranges of values were observed for adiposity variables. HDL cholesterol, triglycerides and fasting glucose in NW males and HDL cholesterol in NW females were significantly correlated with all adiposity variables. For males, higher quintiles of adiposity variables in the NW group and the OW group tended to have higher ORs compared to the first quintiles for the risk factor variables. The fifth quintiles of all adiposity variables had the highest ORs (3.15 for %fat and 3.77 for FM) and they were significantly different from the first quintiles. OW males had ORs similar to those of the fifth quintiles for the risk factor variables. On the other hand, for females, the relatively linear associations were less clear in the NW group. In NW males, the subjects with at least one risk factor had significantly higher %fat and FM than the subjects without risk factors. In NW females, no significant difference was observed for these adiposity variables between the subjects with and without risk factors. CONCLUSION: NW males with elevated adiposity had higher prevalence of risk factors than NW males with less adiposity and the prevalence in the former was rather similar to that seen in OW males. On the other hand, measures of adiposity added little additional information to the BMI classification of NW on CVD risk factors in females.

Adipose Tissue↗

A 12-year follow-up study of treated obese children in Japan.

OBJECTIVE: To assess tracking for body weight from childhood to adulthood in obese Japanese children who were treated for obesity, investigate the relation between the changes in body weight status and morbidity, and identify correlates of the changes in body weight status. STUDY DESIGN: Twelve-year retrospective cohort study. SUBJECTS: A sample of 276 subjects (age 23.9+/-4.1, 176 males and 100 females) who responded to a questionnaire mailed in 1998 to 1047 children (age 10.6+/-2.2) treated for obesity at Mie National Hospital in Japan between 1976 and 1992. MEASUREMENTS: Based on height and weight from medical records during childhood, the relative weight (RW; weight expressed as a percentage of the standard body weight for age, height, and sex) was calculated. Degrees of childhood obesity were based on RW: slight obesity (120% < or = RW<130%; n=17), moderate obesity (130% < or = RW <150%; n=131), and severe obesity (RW > or = 150%; n=128). Adult body mass index (BMI), which was obtained from the mailed questionnaires, was classified as normal, overweight and obese according to the WHO/NIH criteria. Body weight tracking by degree of obesity was evaluated. Subjects with severe obesity during childhood (n=128) were examined for their weight status in adulthood, prevalence of chronic diseases in adulthood, and factors such as parental obesity, dietary and exercise habits and obesity treatment during childhood. RESULTS: Childhood obesity tracked into adulthood obesity or overweight in 54.7% of all cases. Severely obese children (36.7%) were more likely to be obese as an adult than moderately obese children (16.8%). The prevalence of adult obesity tended to be greater in boys with moderate childhood obesity than in girls (29.7% in boys vs 14.9% in girls, P=0.058). Among the severely obese children who became normal-weight adults, the prevalence of chronic diseases was about one-fifth of those who remained obese in adulthood (P=0.041). Four factors were associated with changes in body weight status: maternal BMI at entry (P=0.044), the changes in dietary and exercise habits after treatment (P=0.014, P=0.030, respectively), and satisfaction with obesity treatment in childhood (P=0.035). CONCLUSIONS: Severely obese children have a higher risk of becoming obese adults even when they received obesity treatment in childhood. The risk of adulthood obesity was twice as high in moderately obese boys than in girls. On the other hand, many cases of childhood obesity can be corrected with obesity treatment, which in turn can decrease the risk for adult chronic diseases.

Adolescent↗

[Surgery for synchronous primary lung cancers and intrapulmonary metastases].

Between 1988 and 2000, 1,040 patients with primary lung cancer underwent pulmonary resection at Nagaoka Red Cross Hospital. Thirty-one (2.9%) patients had synchronous primary lung cancer (group A) and 78 patients (7.5%) had intrapulmonary metastases (group B). The 5-year and 10-year survival rate for group A was 64% and 56% respectively and for group B 37% and 32% respectively. The patients in group A showed a better survival rate in the different lobes (80% at 5 years) than in the same lobe (55%), while those in group B gave reverse results (31% and 42%). In group A, the patients had a better survival rate in the different histology (73% at 5 years) than in the same histology (45%). The 5-year survival was 65% for 20 patients with stage I disease, 75% for 4 patients with stage II disease, 43% for 75 patients with stage III and 25% for 10 patients with stage IV. These data suggest that synchronous primary lung cancer had a better prognosis than primary lung cancer with satellite nodules, but the histological discrimination between multiple lung cancers and intrapulmonary metastases was uncertain.

Adult↗

[Surgery for intrathoracic recurrence and second primary tumors in resected lung cancer].

From 1986 to 2000, 42 patients (3.7%) underwent resection for intrathoracic recurrence or second primary lung cancer. Survival in 27 patients with recurrent diseases was 60% at 5 years and 35% at 10 years compared with 65% at 5 and 10 years for 15 patients with metachronous lung cancers morphologically. Ten patients had the second operation less than 2 years since the first operation, 19 patients between 2 and 5 years, and 13 patients more than 5 years, while these 5-year survivals were 72%, 53%, 67% respectively. At the first operation lobectomy was performed in 39 patients (93%), wedge resection or segmentectomy in 3. The reoperation was 14 lobectomy or completion pneumonectomy, 24 wedge or segmentectomy (57%), and 4 other procedures, while these 5-year survivals were 35%, 73%, and 100% respectively. The 5-year survival was 78% for 27 patients with stage I disease and 26% for 10 patients with stage III disease at the first operation, compared with 55% for 30 patients with stage I and 53% for 9 patients with stage III at the reoperation. These data suggest that limited resection is recommended for intrathoracic recurrent diseases and metachronous multiple lung cancers whenever possible.

Adult↗

Exhaled nitric oxide decreases during exercise-induced bronchoconstriction in children with asthma.

Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV(1) and ENO were measured before and at 0, 5, 10, and 15 min after exercise performed on a treadmill for 6 min. EIB was defined as a decrease in FEV(1) of more than 15% after the exercise. Normal children (control group) did not have EIB. Twenty-one patients with asthma had EIB (EIB group) whereas the remaining 18 patients did not (non-EIB group). The baseline ENO value was significantly higher in the asthmatic children than in the normal children, and there was a positive correlation between the maximal percent decrease in FEV(1) and the baseline ENO value (r = 0.501, p = 0.012). At the end of the exercise, ENO had decreased in all the subjects. In the non-EIB and control groups, ENO rebounded to above the baseline at 5 min after the exercise and thereafter. In contrast, ENO remained at a decreased level in the EIB group. The change in ENO did not correlate with the change in minute ventilation, and beta-agonist inhalation at the peak of EIB that accelerated the recovery of FEV(1) did not affect the depressed level of ENO, demonstrating that the reduction of ENO is not a simple consequence of increased ventilation nor airway obstruction. Among the EIB group, steroid-treated patients showed sooner recovery in ENO after the exercise than steroid-naive patients. Our study suggests that NO production in response to exercise may be impaired in patients with EIB, and that ENO represents not only airway inflammation but also a protective function of NO in EIB.

Administration, Inhalation↗

Regulation of catalytic activity of a multifunctional polyketide biosynthetic enzyme, 6-hydroxymellein synthase, by interaction between NADPH and phenylglyoxal-sensitive amino acid residue at the reaction center.

Treatment of 6-hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme in carrot cells, with phenylglyoxal yielded a chemically modified protein in which approximately two moles of the reagent were covalently attached to each subunit of the enzyme. Only NADH- but not NADPH-associated form of native 6-hydroxymellein synthase was inhibited by cerulenin; however, the NADPH-synthase complex lost the insensitivity by the chemical modification of the enzyme protein with phenylglyoxal. Appreciable differences in K(m) values observed between the NADPH- and NADH-associated enzymes were greatly reduced by the treatment with phenylglyoxal. Although the catalytic activity of the NADPH-associated synthase was enhanced by the addition of free CoA, the compound exhibited a significant inhibitory activity to the phenylglyoxal-modified enzyme. A marked deuterium isotope effect in the catalytic reaction of the native synthase-NADPH complex was appreciably decreased in the chemically modified enzyme. These results strongly suggest that an electrostatic interaction between the phosphate group attached to the 2'-position of adenosyl moiety of NADPH and the phenylglyoxal-sensitive amino acid residue, probably arginine, at the reaction center of 6-hydroxymellein synthase regulates several biochemical properties of this multifunctional enzyme.

Acyltransferases↗

Dynamic micro-magnetic resonance imaging of liver micrometastasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd)(64).

DAB-Am64-(1B4M-Gd)(64) is a newly synthesized macromolecular liver magnetic resonance imaging (MRI) contrast agent with a polypropylenimine diaminobutane (DAB) dendrimer conjugated with a bifunctional diethylenetriaminepentaacetic acid (DTPA) derivative for complexing Gd(III) atoms. The characteristics of DAB-Am64-(1B4M-Gd)(64), which quickly accumulated in the liver, have been reported recently. In the present study, the dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was obtained in the mouse liver metastasis model using colon carcinoma cells to evaluate the ability to visualize the micrometastatic tumors compared with that using Gd-DTPA. The dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance the normal liver parenchyma and visualize micrometastatic tumors of 0.3-mm diameter in the liver of the mice with better contrast than that with Gd-DTPA. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a new liver MRI contrast agent potentially useful for diagnosis of micrometastasis in the liver.

Animals↗

3D-micro-MR angiography of mice using macromolecular MR contrast agents with polyamidoamine dendrimer core with reference to their pharmacokinetic properties.

Four novel macromolecular MRI contrast agents, all of which had the same chemical composition but different molecular weights, were prepared using generation-3, -4, -5, and -6 polyamidoamine (PAMAM) dendrimers conjugated with a bifunctional diethylenetriaminepentaacetic acid derivative to change the blood retention, tissue perfusion, and excretion. Size-dependent changes in the pharmacokinetics were observed in the biodistribution study. (153)Gd-labeled generation-6 PAMAM-conjugates remained in the blood significantly longer than all of the other preparations (P < 0.001). The increase in blood-to-organ ratio of the preparations was found to correlate with increasing molecular size (P < 0.001). Additionally, 3D-micro MR images and angiography of mice of high quality and detail were obtained using PAMAM-(1B4M-Gd)x as a macro-molecular MRI contrast agent with a 1.5-T clinical MRI instrument. Numerous fine vessels of approximately 200 microm diameter were visualized on subtracted 3D-MR angiographms with G6D-(1B4M-Gd)(192). The quality of the images was sufficient to estimate the microvasculature of cancerous tissue for anti-angiogenesis therapy and to investigate knockout mice. Magn Reson Med 45:454-460, 2001.

Animals↗

Micro-MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: reference to pharmacokinetic properties of dendrimer-based MR contrast agents.

Pharmacokinetic characteristics of intravascular macromolecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation-7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD-(1B4M-Gd)(2(x+2)) were synthesized with generation-7, -8, and -9 polyamidoamine dendrimers and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D-(1B4M-Gd)(256). In biodistribution and dynamic micro-MRI studies, significantly less renal accumulation of G7D-(1B4M-Gd)(512), G8D-(1B4M-Gd)(1024), and G9D-(1B4M-Gd)(2048) was shown compared to G6D-(1B4M-Gd)(256) (P < 0.01). There was a significantly greater accumulation of G8D-(1B4M-Gd)(1024) and G9D-(1B4M-Gd)(2048) in the liver compared to G6D-(1B4M-Gd)(256) and G7D-(1B4M-Gd)(512) (P < 0.01). The highest blood retention of all dendrimer-based MRI contrast agents was exhibited by G7D-(1B4M-Gd)(512) (P < 0.01). The normal and intratumoral fine vessels of approximately 100 microm diameter were visualized in normal or tumor-bearing mice by high resolution three-dimensional-micro-MR angiographs with G7D-(1B4M-Gd)(512) and G8D-(1B4M-Gd)(1024) with good vessel-to-soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimer-based MRI contrast agents.

Analysis of Variance↗