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Biomedical subjects

A Eguchi

Publications and source records attributed to A Eguchi.

At least 19 recordsLinked to original sources

Electromyographic activity of selected trunk muscles during bicycle ergometer exercise and walking.

Recently, active treatment such as exercise has been increasingly advocated for CLBP (chronic low back pain). Specially, exercise to improve fitness has been recommended for the prevention of back injuries. The bicycle ergometer or walking have often been used to improve the fitness of CLBP patients. However, little is known about the activity levels of the trunk muscles during such exercise. In this study, the electromyographic (EMG) activities of the trunk muscles during bicycle ergometer exercises and walking were compared and the load level on these muscles during such exercises was investigated. The present study provides basic information concerning fitness exercise in CLBP patients. Eleven healthy male volunteers (21.7 +/- 2.5 years old) without low back pain participated in the study. Bipolar surface electrodes were attached to the right side of the rectus abdominis, the obliquus externus abdominis and lower back extensor muscles (L3). EMG signals were continuously recorded while walking and during gradual loading exercises and normalized to maximal voluntary contractions (% MVC). One way analysis of variance (ANOVA) was performed on the % MVC from each exercise and walking for each of the three trunk muscle sites (p < 0.05). The rectus abdominis muscle showed activity of about 6% MVC during any grade of exercise and walking and no significant differences were found between these forms of exercise. The obliquus externus abdominis muscle showed about 30% MVC during any grade of exercise and walking, but no significant difference was found between them. The low back muscles showed activity of about 12% MVC while walking, whereas activity level increased as the exercise load using the bicycle ergometer increased. More significant low back muscles activity was observed while walking than during exercises of 25 w and 50 w. The results of this study indicated that exercise using the bicycle ergometer should be useful for maintaining or improving fitness in CLBP patients, because it results in less load on the trunk muscles and relatively more oxygen uptake than walking.

Abdominal Muscles↗

Effect of static stretch on fatigue of lumbar muscles induced by prolonged contraction.

Low back pain (LBP) is believed to be the result of fatigue of the back extensor muscles induced by prolonged contraction. Although static stretch has been considered to promote recovery from such muscle fatigue by relaxation, little is known about the effect of stretch on muscle fatigue, especially in the back extensor muscles. The purpose of this study was to investigate the effect of static stretch on prolonged contraction-inducedfatigue of the back extensor muscles using electromyographic (EMG) spectral analysis in ten healthy volunteers. Bipolar surface electrodes were placed on the longissimus and the multifidus muscles. EMG signals were collected during two trials of a Sorensen trunk-holding test for two minutes, with a five-minute rest period between the two trials (control test). All subjects were asked to perform the same trials, with one-minute of static stretch and a four-minute rest period (stretch test). Maintaining the knees toward the chest in supine position resulted in static stretch. The median frequency (MF) was calculated using a spectrum analysis program, and the MF slope over time was computed by linear regression analysis, and normalized with the y-intercept. The decreasing rate of the normalized MF slope between two trials in two tests was compared. The decreasing rate of the normalized MF slope of the second trial was larger than that of the first trial in the control test (p < 0.05), but no significant difference was observed in the stretch test. The results indicated that static stretch had a significant effect on the recovery from fatigue of the back extensor muscles, since it influenced the decreasing rate of the normalized MF slope.

Adult↗

Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells.

The plasma membrane of mammalian cells is one of the tight barriers against gene transfer by synthetic delivery systems. Various agents have been used to facilitate gene transfer by destabilizing the endosomal membrane under acidic conditions, but their utility is limited, especially for gene transfer in vivo. In this article, we report that the protein transduction domain of human immunodeficiency virus type 1 Tat protein (Tat peptide) greatly facilitates gene transfer via membrane destabilization. We constructed recombinant lambda phage particles displaying Tat peptide on their surfaces and carrying mammalian marker genes as part of their genomes (Tat-phage). We demonstrate that, when animal cells are briefly exposed to Tat-phage, significant expression of phage marker genes is induced with no harmful effects to the cells. In contrast, recombinant phage displaying other functional peptides, such as the integrin-binding domain or a nuclear localization signal, could not induce detectable marker gene expression. The expression of marker genes induced by Tat-phage is not affected by endosomotropic agents but is partially impaired by inhibitors of caveolae formation. These data suggest that Tat peptide will become a useful component of synthetic delivery vehicles that promote gene transfer independently of the classical endocytic pathway.

Amino Acid Sequence↗

Nuclear targeting of DNA.

The nuclear membrane is a tight barrier for cytoplasmic proteins, but nuclear proteins have the intrinsic ability to overcome this barrier by an active signal-mediated process. Specific cytoplasmic carrier proteins have the responsibility to escort these proteins into the nucleus through the nuclear pore. The nuclear membrane is also a tight barrier for exogenous DNA delivered by synthetic vehicles, while many of the karyophilic viruses have a mechanism to actively deliver their genome through the nuclear pore. Virus DNA and RNA cannot move into the nucleus by themselves and require the viral structural proteins for efficient nuclear transport. In this article, we review the recent progress in understanding the mechanism of the nuclear transport of proteins and the virus genome, and discuss the possibility of developing synthetic gene-delivery systems based on these outcomes.

Active Transport, Cell Nucleus↗

TRF1 is a critical trans-acting factor required for de novo telomere formation in human cells.

The duplex telomere repeat (TTAGGG)(n) is an essential cis-acting element of the mammalian telomere, and an exogenous telomere repeat can induce chromosome breakage and de novo telomere formation at the site of a break (telomere seeding). Telomere seeding requires the telomere repeat (TTAGGG)(n) more stringently than does an in vitro telomerase assay, suggesting that it reflects the activity of a critical trans-acting element of the functional telomere, in addition to telomerase. Furthermore, telomere seeding is induced at a frequency fluctuating widely among human cell lines, suggesting variation in the activity of this hypothetical factor among cells. In this study, we investigated the cellular factor(s) required for telomere formation using the frequency of telomere seeding as an index and identified TRF1, one of the telomere repeat binding proteins, as an essential trans-acting factor. The exogenous telomere repeat induces telomere formation at a frequency determined by the availability of TRF1, even in telomerase-negative cells. Our study shows clearly that TRF1 has a novel physiological significance distinct from its role as a regulator of telomere length in the endogenous chromosome. The possible role of TRF1 in cell aging and immortalization is discussed.

Base Sequence↗

Effect of toluene inhalation on astrocytes and neurotrophic factor in rat brain.

Toluene, an abused substance in Japan, is a neurotoxic chemical that has been shown to have neurobehavioral and electrophysiological effects. In previous work, both acute and chronic effects of toluene on cells have been studied extensively. However, although glial cells are thought to play an important role in the survival of neurons in the brain, the effect of toluene on glial cell function has not yet been characterized. To elucidate this, the effect of toluene inhalation on astrocytes in rat brain was examined. Toluene exposure (1500 ppm for 4 h on 4-10 days) augmented glial fibrillary acidic protein (GFAP) immunoreactivity, particularly in the hippocampus and cerebellum. Quantitative analysis showed that toluene inhalation markedly enhanced GFAP expression in the hippocampus and cerebellum. In both regions, proliferating cell nuclear antigen (PCNA) showed no obvious changes, but glutamine synthetase (GS)-immunoreactive cells were markedly increased by toluene exposure. Thus, the elevation of GFAP expression was induced by astrocyte activation rather than by cell proliferation. If toluene exposure activates astrocytes, astrocytes may play a role in the neurophysiological changes observed in toluene intoxication. A neurotrophic factor, basic fibroblast growth factor (b-FGF) was observed immunohistochemically in the capillary vessel walls in the hippocampus and the cerebellum of toluene-intoxicated rats. Basic-FGF may have induced GFAP expression both in the hippocampus and the cerebellum. So, other neurotrophic factors may affect the difference of GFAP elevation between the hippocampus and the cerebellum. These differences may relate to neurobehavioral function of each brain part after toluene exposure.

Acute Disease↗

Identification and characterization of cell lines with a defect in a post-adsorption stage of Sendai virus-mediated membrane fusion.

In the early stage of infection, Sendai virus delivers its genome into the cytoplasm by fusing the viral envelope with the cell membrane. Although the adsorption of virus particles to cell surface receptors has been characterized in detail, the ensuing complex process that leads to the fusion between the lipid bilayers remains mostly obscure. In the present study, we identified and characterized cell lines with a defect in the Sendai virus-mediated membrane fusion, using fusion-mediated delivery of fragment A of diphtheria toxin as an index. These cells, persistently infected with the temperature-sensitive variant Sendai virus, had primary viral receptors indistinguishable in number and affinity from those of parental susceptible cells. However, they proved to be thoroughly defective in the Sendai virus-mediated membrane fusion. We also found that viral HN protein expressed in the defective cells was responsible for the interference with membrane fusion. These results suggested the presence of a previously uncharacterized, HN-dependent intermediate stage in the Sendai virus-mediated membrane fusion.

Animals↗

A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer.

Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium ion channel family, and its site-directed active mutant (MDEG-G430F) induces massive Na+ influx into cells, leading to cell ballooning and cell bursting. We attempted a novel therapeutic approach for gastric cancers by transferring MDEG-G430F into cancer cells using tumor-specific promoters. In carcinoembryonic antigen (CEA)-producing gastric cancer cells, the level of cell death observed when MDEG-G430F was used with a CEA promoter was similar to that observed when using a potent nonspecific promoter such as the cytomegalovirus promoter. In an in vivo study, fusogenic liposome complexes containing MDEG-G430F driven by the CEA promoter were injected intraperitoneally into CEA-producing gastric cancer cells in a mouse peritoneal dissemination model. Although all 15 of the control mice were dead by 50 days postinoculation, 13 of the 15 mice treated with MDEG-G430F survived. These results indicate that transferring MDEG-G430F into cancer tissues using tumor-specific promoters can achieve striking and selective cancer cell death irrespective of the transcriptional efficiency of the promoters used in vivo, and suggest that this approach is a promising new strategy for cancer gene therapy.

Acid Sensing Ion Channels↗

HSP70 and c-Fos expression of brain stem hypoglossal nucleus in drowning.

The brain stem hypoglossal nucleus (HN) is the center of nerves innervating the upper respiratory tract and is related to control of mastication, deglutition, speech and respiration. To elucidate the relationship between asphyxia and the HN, we investigated the change of hypoglossal neurons in cases of hanging, strangulation, smothering, choking, drowning and respiratory failure. Using immunohistochemical techniques, we observed the brain stem HN with antibodies against microtubule-associated protein 2 (MAP2), muscarinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). MAP2, a cytoskeletal protein of the neuron, is a marker of neuronal damage. Muscarinic AChR was used as a marker of neuronal membrane and ACh signaling. We employed both HSP70 and c-Fos as markers of stress- or damage-related events. We measured the percentage of immunopositive neurons in total neurons of HN. Drowning produced higher expression of HSP70 and c-Fos than other causes of asphyxia, suggesting that drowning induces more severe damage in HN neurons. Furthermore, it was suspected that neuronal changes in drowning might relate to functions of the HN. These observations indicate that immunohistochemical examination of the brain stem HN could provide useful information for determining the cause of asphyxia.

Brain Stem↗

Target-cell specificity of fusogenic liposomes: membrane fusion-mediated macromolecule delivery into human blood mononuclear cells.

Fusogenic liposome, a unique vector prepared by fusing ultraviolet-inactivated Sendai virus and liposome, is known to efficiently deliver content into various animal cells through membrane fusion. In this study, we examined the target-cell specificity of fusogenic liposome (FL)-mediated macromolecule delivery into human blood cells using diphtheria toxin fragment A (DTA) as a probe. Among the peripheral blood mononuclear cells (PBMC), FL was able to deliver its encapsulates into CD14+ monocytes and CD4-/CD8- T-cells, but not into CD19+ B-lymphocytes, CD4+ T-cells or CD8+ T-cells. The susceptibility of human leukemia cell lines to FL was similar to that of PBMC; the order of the reactivity was U937 (monoblastic leukemia)>MOLT4, Jurkat (T-lymphoma)>Daudi, BALL1 (B-lymphoma)>K562 (erythroblastic leukemia). Interestingly, FL showed similar binding activity to all of these leukemia cell lines. These findings indicate that, among blood cells, monocytes, monoblastic leukemia cells, CD4-/CD8- T-cells and T-lymphoma cells are preferable targets for FL-mediated macromolecule delivery. This is the first demonstration of the existence of non-permissive cells against FL. Our results also suggest that some molecules on target-cells other than the binding targets of SV-derived protein may participate in fusion between FL and cells.

Diphtheria Toxin↗

Gene transfer vectors based on Sendai virus.

A gene delivery system is a fundamental technology used in human gene therapy. In order to treat patients suffering from incurable metabolic diseases, we must be able to deliver genes efficiently in situ and induce stable gene expression in non-dividing tissue cells. However, none of the current gene transfer systems (both viral and non-viral) satisfies this goal. In order to develop a novel gene delivery system that is free from the defects of existing gene transfer vectors, we analyzed natural biological phenomena that involve gene transfer and expression, and made artificial components that mimic the functioning of these systems. Our recent results shed light on three major aspects of gene transfer and expression: (1) the direct delivery of DNA into cytoplasm using fusogenic liposomes, (2) the transfer of DNA from cytoplasm to nucleus with a nuclear localization signal, and (3) the stabilization of DNA in the nucleus as an independent replicon. The possible development of a hybrid vector by combining these components is discussed.

Cell Nucleus↗

Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after hyperthermic isolated limb perfusion in patients with malignant melanoma: an analysis of four cases.

The lymphocytes isolated from perfused or non-perfused circulations before, during, and after hyperthermic isolated limb perfusion (HILP) in the four patients with malignant melanoma were analysed for the expression of CD54 (ICAM-1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the mechanism(s) of the activation of such immunocompetent cells as natural killer (NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte populations expressing CD54 increased significantly 1 day after HILP in the four patients examined. The lymphocyte populations expressing CD58 apparently increased. It was also found that the NK-cell and T-lymphocyte activities increased during or after HILP in the present four cases as observed previously in the other melanoma patients. These results indicate that our HILP system may augment the immunological activities through the mechanisms of the induction of CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients who receive HILP.

Adult↗

[Clinical activity of native valve endocarditis].

We reviewed clinical course and surgical outcome of 31 patients with native valve endocarditis who underwent an operation between 1980 and 1994. In the present study, 15 patients who manifested a neurologic complication associated with endocarditis and/or those who had a periannular abscess were assigned as 'clinical active'. Comparing with non-active group (n = 16), clinical active group included more patients with increased C-reactive protein level and those with histological acute inflammatory reaction on excised valvular tissue. Optimal timing of the operation and surgical procedures for aortic root reconstruction were significant problems in the active group. Actuarial probability of survival at 5 postoperative year was 50.8 and 87.5% in the active and non-active group, respectively. The results suggest our 'clinical activity' is a useful predictor in patients with native valve endocarditis.

Abscess↗

Synchronous multicentric development of hepatocellular carcinoma.

Recently, the multicentric origin of hepatocellular carcinoma (HCC) has been recognized, but its clinical importance has still not yet been clarified. The histological characteristics of small hyperechoic HCCs coexisting in 44 consecutively resected Japanese patients whose main HCCs were < 5.0 cm in size were studied. Twelve small hyperechoic HCCs were found and classified into the following two groups: eight nodules in seven patients (15.9%) were early-stage HCC, and four nodules in four patients (9.1%) were more advanced HCC. Thus, early-stage HCC comprised 66.7% of the small echogenic HCCs. Eight HCCs detected as small hyperechoic lesions (found in 15.9% of the patients) showed varying degrees of fatty change yet proved to be well differentiated and retained the preexisting liver structure of either associated liver cirrhosis or chronic hepatitis. Moreover, the histologic characteristics of the eight early-stage HCCs were different from those of the main HCCs. In conclusion, approximately 15% of HCCs in Japanese patients may have a synchronous multicentric origin, and small hyperechoic lesions should be carefully evaluated. However, in the United States or other areas where the occurrence of fatty liver is common, that advice for small hyperechoic lesions may be overly cautious.

Adult↗

A valid new approach in treating solitary new lesions after resection of hepatocellular carcinoma.

Recent studies have suggested that the appearance of solitary new lesions after a curative resection of hepatocellular carcinoma (HCC) may be closely related to the metachronous multicentric development of HCC. It is therefore extremely important to investigate the histological characteristics of solitary new nodular lesions confirmed to be HCC by an ultrasound (US)-guided needle biopsy. Thirty-five patients with small HCC, < or = 3 cm in diameter, who underwent a curative hepatic resection between 1987 and 1992, were observed for possible recurrence over a period of > or = 1 year. Solitary new lesions confirmed to be HCC were noted in 7 (20.0%) out of 35 cases 10-65 months after operation. All solitary new lesions underwent US-guided needle biopsy, and a histological examination of the biopsy specimen was performed. All seven solitary new lesions were then classified into the following two groups according to the histologic differentiation of biopsy specimens and were found to consist of five well-differentiated HCCs (71.4%) and two moderately differentiated HCCs (28.6%). Three of the five well-differentiated HCCs were accompanied by varying degrees of fatty changes. These morphologic observations suggest that approximately 70% of the solitary new lesions confirmed to be HCC after a curative resection of small HCC may thus be related to the metachronous multicentric origin of HCC. However, it is difficult to estimate the exact incidence of such cases. As a result, curative treatment may sometimes be feasible, even when treating solitary new lesions after resection of HCC. Therefore, we can better evaluate such solitary new nodular lesions after a resection of HCC by means of a histologic evaluation using US-guided needle biopsy.

Adult↗

Early stage hepatocellular carcinoma detected during intraoperative ultrasonography.

OBJECTIVES: Recently, it has been recognized that there are increasing incidences of hepatocellular carcinoma (HCC) multicentricity. Thus, intraoperatively detected hepatic lesions that were once thought to be metastatic lesions now need to be carefully reexamined to determine whether they are true metastatic lesions or the multicentric development of HCC. METHODS: We investigated the histological characteristics of small nodular lesions detected during intraoperative ultrasonography in 33 consecutive patients with small HCC who underwent laparotomy at our institution. RESULTS: Fourteen nodular lesions were found incidentally in 10 of 33 patients (30.3%), and were classified into the following three groups: 11 nodules in nine patients (27.3%) were HCC, two nodules in two patients (6.1%) were hemangioma, and one nodule in one patient (3.0%) was a large regenerative nodule. HCC therefore comprised 78.6% of the intraoperatively detected nodular lesions. Of the 11 HCCs, six were hyperechoic, four were hypoechoic, and one was isoechoic. Five (83.3%) of six small hyperechoic HCCs and two (50.0%) of four hypoechoic HCCs were well differentiated and retained their preexisting liver structure. These findings closely coincide with the characteristics of early stage HCC. Thus, early stage HCC comprised 63.6% of the intraoperatively detected HCC cases. CONCLUSIONS: A certain proportion of small satellite HCCs detected during intraoperative ultrasonography in patients with small HCC, which were previously thought to be metastatic lesions from the main HCC, may instead be early stage HCCs. Such findings would also support the concept of the multicentric development of HCC. Approximately 60% of all small HCC cases detected intraoperatively may be early stage HCC. As a result, it is predicted that the emergence of HCC is either multicentric or unicentric, with early intrahepatic spread, although the former seems to be more common.

Adult↗

Multistep, multicentric, and simultaneous development of hepatocellular carcinoma.

We resected a multiple hepatocellular carcinoma (HCC) which contained portal tracts, showed evidence of an early multistep condition, and a multicentric development of HCC which progressed simultaneously. A preoperative working examination revealed a tumor in S5 of the liver, which was 2.5 cm in diameter. In addition, a "nodule-in-nodule" appearance was seen on the ultrasonographic imaging. At intraoperative ultrasonography, an additional two HCCs were detected. At histologic examination of the resected specimen, the main nodule showed a nodule-in-nodule appearance. In the outer nodule, there was a well-differentiated HCC, while the portal tracts remained. The less-differentiated HCC grew in the inner nodule and was replacing the well-differentiated HCC in the outer nodule. These findings suggests morphological transition in the early stages of the multistep development of HCC. Two additional tumors (1.1 cm and 1.0 cm in diameter) detected at intraoperative ultrasonography proved to be HCCs (grade I) with marked fatty change, and with portal tracts remaining within both the HCCs. Furthermore, both of the HCCs retained their preexisting liver structure. These histologic findings coincided with the characteristics of the early stage HCC, whereas the coexistence of early stage HCCs suggests the multicentric development of HCC. Distortion, compression, and invasion of the portal tracts may appear as the tumor grows, thereby evoking an increasing risk of metastasis via the portal tracts. Therefore, the early diagnosis and treatment of HCC before the portal tracts disappear, when 1.5 cm in size or less, may be very important for surgeons and diagnosticians, as an effective curative resection may be feasible.

Carcinoma, Hepatocellular↗

[A case of early gastric cancer with Virchow's node metastasis, effectively treated by high dose of UFT].

We report a case of early gastric cancer with Virchow's node metastasis. The patient underwent partial gastrectomy and postoperative immunochemotherapy using MMC, 5'-DFUR and PSK, which reduced the Virchow's node. Three years after surgery, we found metastases to the left subclavicular and axillary nodes other than the Virchow's node. Then UFT was administered orally at 600 mg/day, and the metastatic nodes diminished, then vanished. The patient is alive nearly five years after surgery.

Adenocarcinoma↗