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Biomedical subjects

Hideki Suzuki

Publications and source records attributed to Hideki Suzuki.

At least 19 recordsLinked to original sources

Efficacy of tonsillectomy pulse therapy versus multiple-drug therapy for IgA nephropathy.

We evaluated the efficacy of tonsillectomy plus pulse prednisolone, warfarin, and dipyridamole including methylprednisolone pulse (tonsillectomy plus pulse therapy), versus prednisolone, warfarin, and dipyridamole including mizoribine (PWDM) for the treatment diffuse IgA nephropathy (IgAN) in children. The patients were randomly assigned to be treated by tonsillectomy plus pulse therapy for 2 years (Group A, n=16) or PWDM for 2 years (Group B, n=16). The clinical features and pathological findings in both groups were analyzed prospectively. The mean urinary protein excretion after 6 months of treatment in both groups had decreased significantly compared with pre-therapy. The activity index (AI) in both groups was lower at the time of the second biopsy than at the time of the first biopsy. The chronicity index (CI) in Groups A and B did not differ between the first and second biopsy. At the latest follow-up examination none (0%) of the patients in either group had renal insufficiency. None of the patients in Group A, but six patients in Group B experienced an acute exacerbation of IgAN as a result of tonsillitis (P<0.05). In conclusion, although there was no untreated control group in this study, the results suggested that tonsillectomy plus pulse therapy is as effective as PWDM in ameliorating proteinuria and histological severity in IgAN patients and in preventing acute exacerbation of IgAN by tonsillitis.

Adolescent↗

Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor: a case report.

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

Adult↗

The soluble form of human leukocyte antigen class I antigen causes apoptosis on hepatocellular carcinoma cell lines.

A soluble form of human leukocyte antigen class I antigen (sHLA-I) has been reported to cause apoptosis on cytotoxic T cells and inhibit killer activity of natural killer cells via killer-cell inhibitory receptors. However, its effect on cancer cells has not yet been elucidated. We examined the direct effect of sHLA-I on human liver cancer cell lines, HepG2, HLE and HLF. The effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction were evaluated. To elucidate the mechanisms, cDNA expression arrays were also examined. sHLA-I caused cell growth inhibition, resulting in apoptosis on human hepatocellular carcinoma, dose-dependently. In this process, caspase-3 was activated. sHLA-I also inhibited in vivo growth of hepatocellular carcinoma in severe combined immunodeficient mice. sHLA-I caused apoptosis on human hepatocellular carcinoma.

Alternative Splicing↗

Inhibitory effect of thiopental on ultra-rapid delayed rectifier K+ current in H9c2 cells.

Using the whole-cell voltage clamp technique, we investigated the effects of thiopental on membrane currents in H9c2 cells, a cell line derived from embryonic rat heart. Thiopental blocked a rapidly activating, very slowly-inactivating ultra-rapid type I(Kur)-like outward K(+) current in a concentration-dependent manner. The half-maximal concentration (IC(50)) of thiopental was 97 microM with a Hill coefficient of 1.2. The thiopental-sensitive current was also blocked by high concentrations of nifedipine (IC(50) = 9.1 microM) and 100 microM chromanol 293B, a blocker of slowly activating delayed rectifier K+ current (I(Ks)), but was insensitive to E-4031, an inhibitor of rapidly activating delayed rectifier K(+) current (I(Kr)). TEA (tetraethylammonium) at 5 mM and 4-AP (4-aminopiridine) at 1 mM reduced the K(+) current to 30.8 +/- 12.2% and 20.5 +/- 6.5% of the control, respectively. Using RT-PCR, we detected mRNAs of Kv2.1, Kv3.4, Kv4.1, and Kv4.3 in H9c2 cells. Among those, Kv2.1 and Kv3.4 have I(Kur)-type kinetics and are therefore candidates for thiopental-sensitive K(+) channels in H9c2 cells. This is the first report showing that thiopental inhibits I(Kur). This effect of thiopental may be involved in its reported prolongation of cardiac action potentials.

Anesthetics↗

PET evaluation of fatty tumors in the extremity: possibility of using the standardized uptake value (SUV) to differentiate benign tumors from liposarcoma.

OBJECTIVE: The relative utility of various preoperative diagnostic imaging modalities, including PET (utilizing FDG and FMT), CT, and MR imaging, for evaluation of lipoma and liposarcoma, especially well-differentiated liposarcoma, was investigated. METHODS: Imaging findings in 32 patients with histopathologically documented lipoma, including one with fibrolipoma and one with angiolipoma, and 25 patients with liposarcomas whose subtypes included 10 well-differentiated, 10 myxoid, and 5 other types were reviewed retrospectively. Pre-operative imaging included FDG-PET (n = 44), FMT-PET (n = 21), CT (n = 25), and MR imaging (n = 53). RESULTS: Statistically significant imaging features of MR images favoring a diagnosis of liposarcoma involved lesions containing less than 75% fat (p < 0.001) as well as the presence of septa (p < 0.001). As compared with well-differentiated liposarcoma, benign lesions were differentiated significantly only by the presence of septa (p < 0.001), which also provided significant differentiation on CT (p < 0.05). The mean SUVs for malignant tumors were significantly higher than those for benign lesions in both FDG- and FMT-PET analyses (p < 0.0001, p = 0.0011, respectively). By using a cut-off value for FDG- and FMT-PET set at 0.81 and 1.0 respectively, which provided the highest accuracy, benign lesions were differentiated significantly from liposarcomas (p < 0.001, and p < 0.02). Furthermore, benign tumors and the three subtypes of liposarcoma were divided significantly into four biological grades by FDG- and FMT-accumulation rates (rho = 0.793, p < 0.0001; and rho = 0.745, p = 0.0009, respectively). A cut-off value of 0.81 for FDG-PET provided significant differentiation between benign lesions and well-differentiated liposarcoma (p < 0.01). CONCLUSIONS: The presence of septa on MR images differentiated lipomas from liposarcoma, even well-differentiated type. PET analysis, especially FDG-PET, quantitatively provided not only the differentiation but also the metabolic separation among subtypes of liposarcoma. Interpretation of the visual diagnostic modalities requires extensive experience and carries a risk of ignoring a critical portion of malignancy. PET metabolic imaging may be an objective and useful modality for evaluating adipose tissue tumors preoperatively.

Adult↗

An elemental diet controls inflammation in indomethacin-induced small bowel disease in rats: the role of low dietary fat and the elimination of dietary proteins.

Elemental diets (EDs) are effective in treating Crohn's disease. We hypothesize that low dietary fat and amino acids used as the sole nitrogen source are the major contributors for the success of EDs. We examined the influences of the addition of dietary fat and protein to an ED using an indomethacin-induced inflammation model in rat small intestine. In the ED-fed rats, the intestinal damage score was decreased compared with that in the standard chow group with decreasing intestinal permeability. By supplementing an ED with soybean oil (SO), intestinal permeability was increased to a level similar to that of the standard chow group. For this group, the intestinal damage score also increased compared with that of the ED group but did not reach the levels observed in the standard chow group. The addition of dietary proteins (using heat-denatured pancreatin) resulted in intestinal damage scores that were significantly higher than those of the ED+SO-fed group. The dietary protein increased the intestinal damage score. These results suggest that EDs control inflammation by decreasing intestinal permeability and the elimination of dietary proteins.

Animals↗

Production of hybrid 16-membered macrolides by expressing combinations of polyketide synthase genes in engineered Streptomyces fradiae hosts.

Combinations of the five polyketide synthase (PKS) genes for biosynthesis of tylosin in Streptomyces fradiae (tylG), spiramycin in Streptomyces ambofaciens (srmG), or chalcomycin in Streptomyces bikiniensis (chmG) were expressed in engineered hosts derived from a tylosin-producing strain of S. fradiae. Surprisingly efficient synthesis of compounds predicted from the expressed hybrid PKS was obtained. The post-PKS tailoring enzymes of tylosin biosynthesis acted efficiently on the hybrid intermediates with the exception of TylH-catalyzed hydroxylation of the methyl group at C14, which was efficient if C4 bore a methyl group, but inefficient if a methoxyl was present. Moreover, for some compounds, oxidation of the C6 ethyl side chain to an unprecedented carboxylic acid was observed. By also expressing chmH, a homolog of tylH from the chalcomycin gene cluster, efficient hydroxylation of the 14-methyl group was restored.

Macrolides↗

Tightly regulated vectors for the cloning and expression of toxic genes.

A series of low-copy expression vectors that permits the stable maintenance and regulated expression of highly toxic gene products has been developed. These vectors utilize the lactose promoter/operator system, and protect against read-through transcription from other promoters on the plasmid by placement of the rrnB T1T2 terminators upstream of the lactose promoter. For additional regulatory control, the vectors utilize low-copy origins of replication. Either the pMPP6 origin (pSC101-derived) is used for cloning into Escherichia coli or related species, or the broad-host-range RK2 origin of replication is utilized for cloning into the majority of Gram-negative bacteria. The resulting plasmids have no detectable leaky expression. To test these vectors, the genes for the bacteriocidal colicins D, E3, and E7 were cloned and stably maintained in the absence of their immunity genes. Upon induction with isopropyl-beta-D-thiogalactopyranoside (IPTG), cell death was observed, indicating expression of each colicin. These low-copy expression vectors will be useful for the cloning and expression of toxic genes in bacterial systems.

Bacteriological Techniques↗

[Comparison of Work Ability Index and cognitive function tests].

The purpose of this study was to evaluate the effect of aging with regard to scores for certain cognitive function tests and WAI (Work Ability Index), and to examine the relationship between cognitive function test scores and work ability as measured by WAI. The subjects were 139 male employees of a factory producing steel plate, and their average age was 48.1 yr (SD 16.4). The WAI and cognitive function tests were conducted and valid scores were obtained from 134 subjects as to WAI, and from 88 subjects as to cognitive function tests. The subjects were divided into two groups: young workers (under 45 yr) and middle-aged to elderly workers (45 yr and over). The WAI scores of the two groups were compared, but no significant differences were observed. Nevertheless, for two WAI items, WAI-2 and WAI-7, the scores of the middle-aged to elderly worker group were significantly higher than those of the young worker group. In contrast, the scores for WAI-3 of the middle-aged to elderly group were significantly lower than those of the young worker group. The cognitive function test scores for the two groups were also compared. The scores for Working Memory test, Tracking test, and Sentence-to-sentence Comparison test of the middle-aged to elderly worker group were significantly lower than those of the younger group. Moreover, for the middle-aged to elderly worker group, the average WAI-3 scores for those with good cognitive function test results and those with poor cognitive function test results were compared, but there were no significant differences. This result shows that deterioration of physical function caused by aging is not related to deterioration of cognitive function caused by aging in the subjects of this study. The reason for this may be that the subjects are blue-collar workers, and thus cognitive functions are less important for their work.

Adult↗

[Association of working postures and some lifestyles with low back pain in a manufactory].

The aim of this study was to determine the relationship between work and low back pain (LBP) by examining both working postures and the workers' everyday lifestyle. Subjects were 118 male workers in a small-to-medium-sized factory having three kinds of workplaces: the slit line, the packing line, and the crane unit. Working posture analysis with OWAS and interviews were carried out. The result of posture analysis showed that the standing posture with both legs straight and back bent appeared most frequently in all three workplaces. Meanwhile, the prevalence of LBP was almost equal among these groups, with 70% of workers having experienced LBP in each group. But the main cause of LBP differed among the three groups. On the slit line, the result of regression analysis and interview suggested that exercises in the past affected the prevalence of LBP, and that aging and work made LBP worse. On the packing line, many workers were transferred to other positions after a few years, and thus might affect the prevalence of LBP in other workplaces. For the crane unit, it appeared that work in previous positions might affect the occurrence of LBP. Moreover, it seemed that activities in the workplace, rather than lifestyles, contribute to the occurrence of LBP in this factory.

Adult↗

Relationship between intraduodenal 5-hydroxytryptamine release and interdigestive contractions in dogs.

BACKGROUND: 5-hydroxytryptamine (5-HT) is released into the intestinal lumen during the fasting state. However, the relationship between the intraduodenal 5-HT and the interdigestive cyclic motor activity in conscious dogs is unclear. AIM: To correlate intraduodenal 5-HT concentrations with the interdigestive gastroduodenal migrating motor complex (MMC). METHODS: 6 dogs were implanted with 2 force transducers for recording gastroduodenal contractions and 2 catheters for measuring duodenal volume by a non-absorbable marker perfusion technique. Intraduodenal 5-HT concentrations were determined by high performance liquid chromatography at 5-min intervals. RESULTS: During fasting, gastroduodenal motor activity cycled as the MMC; luminal 5-HT concentrations and total outputs varied cyclically in temporal association with the MMC. Mean 5-HT concentrations peaked during phase II (P<0.05 vs. phase I and III), and 5-HT outputs during phases II or III were greater than during phase I (P<0.05). Exogenous motilin (0.3 microg/kg-hr, IV) stimulated 5-HT release into the duodenal lumen with peak values (P<0.05) during motilin-induced phase II and III. Gastroduodenal motor activity was not altered, however, during exogenous intraduodenal administration of 5-HT (300 ng/mL-min). CONCLUSIONS: 5-HT is released cyclically into the duodenal lumen in close temporal association with the MMC, but its physiologic significance in regulation of gastroduodenal motility is unknown.

Animals↗

Expression of EphA2 and E-cadherin in colorectal cancer: correlation with cancer metastasis.

Recently, overexpression of EphA2, a member of the Eph family of receptor tyrosine kinases, has been reported in several cancers. Reduced expression of E-cadherin, an intercellular adhesion molecule of epithelial cells, has been reported to be associated with aggressive clinicopathological phenotypes in various cancers. In epithelial cells, EphA2 and E-cadherin co-localize to sites of cell-cell contact, and it has been shown that E-cadherin regulates EphA2. This study aimed to clarify the relationship between the expression of the EphA2 and E-cadherin proteins and clinicopathological characteristics, with reference to the expression levels of both EphA2 and E-cadherin, in patients with colorectal cancer. We performed immunohistochemical staining of EphA2 and E-cadherin with EphA2 and E-cadherin monoclonal antibodies in samples from 194 primary lesions of colorectal cancer. The expression level of EphA2 had a statistically significant relationship with liver metastasis, lymphatic vessel invasion and clinical stage (p=0.0477, 0.0316 and 0.0467, respectively). In addition, the positivity rate of EphA2 was significantly higher in primary lesions with lymph node metastasis than in those without metastasis (p=0.0014). However, the expression level of E-cadherin had an inverse relationship with both differentiation level of the tumor and lymphatic vessel invasion (p=0.0430 and 0.0320, respectively). Furthermore, a significant relationship between the expression of EphA2 and E-cadherin was observed. In conclusion, our study revealed that the overexpression of EphA2 protein in colorectal carcinoma tissue correlates closely with cancer progression and hematogenous and lymphogenous metastasis, suggesting that both EphA2 and E-cadherin may play an important role in tumor metastasis in colorectal cancer.

Adult↗

Antitumor effect of a splenic injection of 5-fluorouracil on metastatic liver cancer in mice.

The regional administration of 5-fluorouracil (5-FU) has been the fundamental therapy against liver metastases for the improvement of patient prognosis; however, there have been few reports about the immunological effects of this agent. It is also unknown whether it affects the spleen, one of the major lymphoid organs. The objective of the present study was to determine the immunological effect of an intrasplenic injection of 5-FU against liver metastases. We investigated the effect of an intrasplenic injection of 5-FU on the formation of experimental liver metastasis resulting from an intraportal vein injection of colon 26 carcinoma cells in BALB/c mice and elucidated some of the underlying mechanisms involving the effects of this on cellular immunity. Liver metastases were significantly diminished by the splenic injection of 5-FU, particularly in comparison with the portal injection or systemic administration. This was followed by augmentation of the interleukin-12 (IL-12) level in the spleen and activation of hepatic mononuclear cells. In those cells, NK1.1+ (NKT) cells played a central role against metastases. A splenic injection of 5-FU is more effective on the involution of liver metastases than portal or systemic injection. This effect may be attributed to the augmentation of the IL-12 level in the spleen and of NKT cells in the liver rather than to the original effect of 5-FU, which is the so-called inhibition of DNA synthesis.

Animals↗

Effect of motilin on endogenous release of insulin in conscious dogs in the fed state.

The aim was to investigate the insulin-releasing activity of motilin during and after feeding. A single intravenous bolus injection of motilin (0.01-0.3 microg/kg) dose-dependently stimulated endogenous release of insulin in the postprandial state. The insulin-releasing activity of motilin in the fed state was completely abolished by pretreatment with atropine or hexamethonium and was partly inhibited by ondansetron. Truncal vagotomy also greatly suppressed the motilin-induced insulin release. While phentolamine significantly enhanced insulin release in response to motilin, propranolol significantly inhibited this response in both states. The motilin-induced insulin release in the fed states was not accompanied by any changes in glucose concentrations. In conclusion, while the physiological significance remains unclear, these results indicate that physiological doses of motilin stimulate endogenous release of insulin via a vagally cholinergic muscarinic pathway, and that adrenergic and 5-hydroxytryptamine3 receptors are also involved in this response, in the dog.

Animals↗

Age-related differences in the effect of running training on cardiac Myosin isozyme composition in rats.

We examined the effect of running training on age-related changes in cardiac myosin isozyme composition in rats. Female Fischer 344 rats (6, 12, 20, and 27 months old) were divided into two groups: sedentary control and trained. The trained group rats were trained by treadmill running for up to 60 minutes per day, 5 days per week for 8 weeks at up to 30 m per minute. In sedentary control rats, the proportion of V1 myosin, that is, alpha-myosin heavy chain (MyHC) isoform, decreased progressively from 6 to 27 months of age. In the younger age groups (6 or 12 months old), there was a shift from V1 myosin to V3 myosin (beta-MyHC isoform) in trained hearts. However, the training program did not induce a cardiac myosin isozyme transition in older rats (20 or 27 months old). These results suggest that the mechanisms mediating the responses of cardiac muscle to running training alter during aging.

Aging↗

Image Fusion System Using PACS for MRI, CT, and PET Images.

This paper presents and evaluates Picture Archiving and Communication System (PACS) and its interaction with the image fusion applications using positron emission tomography (PET), CT, and MRI, as well as some clinical applications of fusion images. A network connections between medium-sized PACS involving CT, MRI, SPECT, and PET were developed. Image registration and fusion was achieved in the PET's workstation by Advanced Visual System (AVS) software. Reconstructed datasets of CT, MRI, SPECT, and PET were transferred and archived in PACS servers. Series of anatomical images of CT and MRI were fused with metabolical images of PET with (18)F labeled fluoro-2-deoxy-D-glucose (FDG). Throughput rate of image data, as well as clinical applications of fusion images were evaluated and correlated with phantom studies. The average throughput rate of archiving and processing steps was 0.45 Mbps, 0.77 Mbps, respectively. Image fusion experiment using phantom and patients' data showed high accuracy in all directions. The combination of PACS and image fusion provided very useful clinical tools and made it quite easy to maximize the benefit from the diagnostic imaging.

Journal Article↗

Positron emission tomography imaging of musculoskeletal tumors in the shoulder girdle.

The shoulder girdle presents unique features for the preoperative planning of musculoskeletal tumors. This is the first trial to evaluate positron emission tomography (PET) analysis for preoperative planning in shoulder girdle tumors. Fifty-two patients were examined with fluorine 18 fluoro-2-deoxy-D-glucose (FDG)-PET and/or alpha-methyltyrosine (FMT)-PET. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) were generated. FDG-PET may be useful for the detection of malignant tumors and screening for metastatic spread, with the qualitative assessment of heterogeneous biologic activity providing a correct approach for biopsy. The mean SUVs for malignant tumors were significantly higher than those for benign lesions. However, a useful cutoff SUV was not found in either FDG- or FMT-PET for differentiating malignant from benign tumors from receiver operating characteristic curve analysis. SUVs on FDG- and FMT-PET may merely be limited to differentiating malignant from benign tumors in the shoulder girdle.

Adolescent↗

A novel antibacterial gene transfer treatment for multidrug-resistant Acinetobacter baumannii-induced burn sepsis.

Sepsis caused by multidrug-resistant bacterial infections in critically injured patients has become a major clinical problem. Recently, Acinetobacter baumannii (AB) wound infections, especially in our critically injured soldiers fighting in Iraq and Afghanistan, is posing a major clinical problem and an economic burden. ConjuGon, Inc., has developed a novel antibacterial therapeutic technology using bacterial conjugation. The donor cells are attenuated Escherichia coli carrying a conjugative plasmid. The expression of bactericidal genes cloned on the plasmid is tightly repressed in the donor cells but becomes de-repressed once mobilized into a pathogen and disrupts protein synthesis. Here, we tested the efficacy of this novel conjugation technology to control and eradicate a drug-resistant clinical isolate of AB wound infection both in vitro and in a murine burn sepsis model. C57Blk/6J mice were divided into burn (B) and burn sepsis (BS) groups. All animals received a 12% TBSA dorsal scald full-thickness burn. The BS group was inoculated with multidrug-resistant AB (1 x 10(5) colony-forming units [CFU]) at the burn wound site. BS animals were either untreated or treated with increasing concentrations (10(3) - 19(10) CFU) of attenuated donor E. coli encoding bactericidal proteins. The survival rate was monitored for 10 days. The ability of donor cells to significantly diminish AB levels in the burn wound 24 hours after injury was determined by quantitative cultures. Donor cells were highly effective in killing AB in vitro. In the burn sepsis model, 90% B group animals survived, and 40% to 50% BS animals survived with no treatment in 5 to 6 days. Treatment with donor cells at 10(10) to 10(6) provided significant survival advantage (P < .05). Quantitative cultures of burn wounds revealed that AB numbers increased from 3 x 10(4) CFU to 7.8 +/- 4.4 x 10(9) CFU in 24 hours in the untreated group. Single treatment with donor cells (10(10) CFU) significantly reduced AB in the burn wound to less than the levels seeded into the wound (1.23 +/- 0.5 x 10(4) CFU; P < .05). Taken together, these results indicate that this novel technology is an efficient method to control drug-resistant AB burn wound infections and prevent their systemic spread.

Acinetobacter baumannii↗