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Biomedical subjects

T Abe

Publications and source records attributed to T Abe.

At least 199 records · Page 11Linked to original sources

Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells.

Several reports of clinical trials of immunotherapy using dendritic cells have been published to date. In this study, we investigated the safety and clinical response of immunotherapy with fusions of dendritic and glioma cells for the treatment of patients with malignant glioma. Eight patients with malignant glioma, ranging in age from 4 to 63 years old, participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells of dendritic and glioma cells were prepared with polyethylene glycol, and the fusion efficiency ranged from 9.2 to 35.3% (mean, 21.9%). All patients received the fusion cells every three weeks for a minimum of 3, and a maximum of 7, immunizations. Fusion cells were injected intradermally, close to a cervical lymph node. The percentage of CD16- and CD56-positive cells in peripheral blood lymphocytes slightly increased after immunization in 4 out of 5 cases investigated. Peripheral blood mononuclear cells were incubated with irradiated autologous glioma or U87MG cells and supernatants were harvested. In 6 cases analyzed, the concentration of interferon-gamma in the supernatant increased after immunization. Clinical results showed that there were no serious adverse effects and two partial responses. Although the results of the phase I clinical trial of fusion cells indicated that this treatment safely induced immune responses. we were unable to establish a statistically significant treatment-associated response rate, due to the limited sample population. Therefore, further evaluation of the role of adjuvant cytokines is necessary.

Adult↗

Agranular CD4+CD56+ blastic natural killer leukemia/lymphoma.

Blastic natural killer cell leukemia/lymphoma (blastic NKL/L) is characterized by blastic morphology and a distinctive immunophenotype combining blastic features and cytologically resembling acute myeloid or lymphoid leukemia. The clinical, pathologic, and cytogenetic features of blastic NKL/L have not yet been systematically identified. We report herein a case of blastic NKL/L with skin lesion, adenopathy, and systemic lymphoadenopathy. The identified tumor cells were positive for CD4 and CD56, and negative for T-cell, B-cell, and myeloid markers. T-cell receptor beta, gamma, delta, and immunoglobulin heavy chain genes in the bone marrow cells showed germ-line configurations. Southern blot analysis with a terminal probe did not reveal any Epstein-Barr virus infection. Although patients diagnosed as blastic NKL/L have generally shown chemotherapy resistance and poor prognosis, our patient was treated with a combined chemotherapy, which is also used for acute lymphoblastic leukemia, and has maintained complete remission (CR) for more than 13 months. In addition to clinical investigations, we thoroughly analyzed his karyotype by using a combination of G-banding and a new technique, spectral karyotyping. The karyotype was described as 45, XY, der(1)t(1;20)(p32;q11.2), der(6) (1pter-->1p32:: 6p21.1-->6q13:: 7q11.2-->7qter), der(7) t(7;20)(q11.2;q11.2), t(13;14)(q14;q32), der(13)t(6;13) (p21.1; q14), -20.

Adult↗

Primary natural killer cell lymphoma of the lacrimal sac.

Primary lymphoid tumors of the lacrimal sac are quite rare, and all reported cases are of B-cell tumors with good prognosis. To our knowledge, this is the first case of primary natural killer (NK) cell lymphoma of the lacrimal sac. A 55-year-old woman presented with a lacrimal sac tumor, and histological diagnosis of NK cell lymphoma was made. Although disease was initially localized to the right lacrimal sac, it invaded into the adjacent ethmoidal sinus before chemotherapy was initiated (clinical stage IIE). Epstein-Barr virus (EBV)-encoded small RNA (EBER) was detected in lymphoma cells by in situ hybridization. Systemic chemotherapy combined with intrathecal chemotherapy followed by local radiotherapy was performed, and the patient achieved complete remission. However, shortly after completion of chemoradiotherapy, the lymphoma relapsed with rapid systemic dissemination. The disease was refractory to chemotherapy, and the patient eventually succumbed due to sepsis.

Antineoplastic Combined Chemotherapy Protocols↗

Regulation of H(+)-ATPase synthesis in response to reduced pH in ruminal bacteria.

The capacity of ruminal bacteria to regulate H(+)-ATPase synthesis in response to reduced pH was investigated to explain acid tolerance. The activity of H(+)-ATPase in Streptococcus bovis, an acid-tolerant bacterium, was 2.2-fold higher at pH 4.5 than at pH 5.5. The increase in the amount of H(+)-ATPase protein was similar, suggesting that the increase in H(+)-ATPase activity is owing to the increase in H(+)-ATPase synthesis. The level of atp-mRNA at pH 4.5 was 2.5-fold higher than at pH 5.5, indicating that H(+)-ATPase synthesis is regulated at the transcriptional level, responding to low pH. In Ruminococcus albus, an acid-sensitive bacterium, H(+)-ATPase activity, the amount of H(+)-ATPase protein, and the level of atp-mRNA at pH 7.0 were similar to the values at pH 6.0, the lowest pH permitting growth. This result suggests that R. albus is incapable of enhancing H(+)-ATPase synthesis at low pH. Thus, acid tolerance appeared to be related to the capacity to augment the synthesis of H(+)-ATPase responding to low pH.

Animals↗

High cyclin E/low p27Kip1 expression is associated with poor prognosis in astrocytomas.

Cyclin E and p27Kip1 are co-regulators of the G1- to S-phase transition and closely related to tumor behavior. The purpose of this study was to examine expression of cyclin E and p27Kip1 in astrocytomas and to evaluate the relationships between expression of these cell-cycle regulators and prognosis of patients with astrocytoma. Tissue samples from 130 astrocytomas (WHO grade 1 n = 5, grade 2 n = 23, grade 3 n = 64, grade 4 n = 38) were examined immunohistochemically for cyclin E and p27Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The cyclin E labeling index (LI) tended to increase with tumor grade (Kruskal-Wallis, P = 0.0104). For patients with primary astrocytomas, the 50% survival times for the low cyclin E LI (< 5%) group and the high cyclin E LI (> or = 5%) group were 53.7 months and 19.8 months. In combined analysis of cyclin E and p27Kip1 expression, the low cyclin E/high p27Kip1 LI (> or = 50%) group had the best survival (50% survival time: 103.2 months), the low cyclin E/low p27Kip1 LI (> or = 50%) and the high cyclin E/high p27Kip1 LI groups moderate survival (24.1 and 27.5 months), and the high cyclin E/low p27Kip1 LI group the worst survival (13.1 months). Multivariate analysis identified the combined factor, high cyclin E/low p27Kip1, as a novel independent prognostic factor for survival time (P = 0.0037, relative risk = 2.4). This study suggested that combined analysis of cyclin E and p27Kip1 expression was considered to be potentially useful in predicting the prognosis of patients with astrocytoma.

Adolescent↗

Silent mixed corticotroph and somatotroph macroadenomas presenting with pituitary apoplexy.

We discuss three unique cases of pituitary macroadenoma presenting with pituitary hemorrhage but without typical endocrine symptomatology. Immunohistochemical analysis indicated positive reactivity for adrenocorticotropic hormone (ACTH) and growth hormone (GH), and in situ hybridization indicated the expression of proopiomelanocortin (POMC) and GH mRNA. We designated these cases silent mixed corticotroph and somatotroph adenoma. Patient 1 was a 30-year-old man, patient 2 was a 29-year-old woman, and patient 3 was a 59-year-old woman. All patients presented with a headache of sudden onset and visual disturbance. The patients did not exhibit typical Cushing's or acromegalic features. Serum ACTH level was remarkably elevated in patient 1, and slightly elevated in patients 2 and 3. In all patients, serum GH levels were within normal range and magnetic resonance imaging revealed an intra- and suprasellar mass with pituitary hemorrhage. Transnasal pituitary surgery in the three patients disclosed a pituitary adenoma producing ACTH and GH. In patient 2, the residual adenoma reappeared along with an intratumoral hemorrhage, and was resected by secondary transnasal surgery. Silent mixed corticotroph and somatotroph adenomas are characterized by the following: no endocrine symptoms; presentation dominated by mass effect symptoms; macroadenoma presenting with acute pituitary hemorrhage; and production of both ACTH and GH.

Adenoma↗

Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration.

BACKGROUND: Retinal pigment epithelial (RPE) cells have been transplanted to replace the RPE cells lost after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration. The purpose of this study was to analyze the visual function of eyes with altered RPE after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration, and to determine the effect of proliferated or migrated RPE cells on visual function. METHODS: Forty-seven patients with age-related macular degeneration underwent excision of CNVs following vitrectomy and tamponade with sulfur hexafluoride (SF6) or silicone oil. The appearance of pre- or subretinal fibrosis and pigmentation of the lesion was considered to indicate proliferation and migration of RPE cells. Microperimetry was also performed. RESULTS: A significant correlation was found between the size of CNVs removed by surgery and the size estimated by indocyanine green angiography (P=0.0126). The mean number of RPE cells lost was estimated at 1.52 x 10(4). Pre- or subretinal fibrosis or pigmentation was observed in 37 patients (75.5%). The number of eyes with fibrosis was significantly higher in eyes with silicone oil tamponade than with SF6 tamponade (P=0.0016). A statistically significant correlation was not found between the presence of fibrosis or pigmentation and the postoperative visual acuity. Not all patients used the area of pigmentation for fixation, and microperimetry showed that some of the patients had scotomas in well-pigmented areas. CONCLUSIONS: Fibrosis and pigmentation after excision of CNVs may not always indicate normal function in these areas. These observations are especially relevant for transplantation of pigment epithelial cells in the future.

Aged↗

Ophthalmological findings in patients with spinocerebellar ataxia type 1 are not correlated with neurological anticipation.

BACKGROUND: Optic atrophy, attenuation of the oscillatory potentials (OPs) of the electroretinogram (ERG), and enlargement of corneal endothelial cells, have been reported in patients with spinocerebellar ataxia type 1 (SCA1). These patients have a trinucleotide repeat expansion in the SCA1 gene and show neurological anticipation. The purpose of this study was to determine whether the ophthalmological findings are correlated with the neurological disorders, and whether ophthalmological anticipation is present in patients with SCA1. METHODS: The visual acuity, ERGs, and corneal endothelial cell density were examined in 14 patients whose DNA analysis revealed an expanded trinucleotide repeat in an allele of the SCA1 gene. The results of the tests were compared with the trinucleotide repeat number and the duration of the neuronal disease. RESULTS: The neurological disorders in the patients showed anticipation. The negative correlation between the trinucleotide repeat number and the neurological disorder was statistically significant (P<0.0001). However, the correlations between trinucleotide repeat number and visual acuity, amplitude of OPs, and corneal endothelial cell density were not significant. Statistically significant correlations were found between the duration of the neuronal disease and the visual acuity, OPs, and corneal endothelial cell density (P<0.0001, P=0.0004, and P<0.0001, respectively). The ophthalmological disorders were prominent in patients who had neuronal disease for more than 10 years. CONCLUSION: Unlike the neurological findings, the ophthalmological disorders in patients with SCA1 were not correlated with the trinucleotide repeat number of the SCA1 gene. The ophthalmological findings were most highly correlated with the duration of the neuronal disease.

Adult↗

Architectural characteristics of dominant leg muscles in junior soccer players.

The preferential use of dominant over non-dominant limbs produces muscle hypertrophy in the dominant limb. The purpose of this study was to investigate the architectural characteristics of the muscle that are associated with dominant leg use in junior soccer players. Fascicle length, pennation angle and muscle thickness of the medial gastrocnemius (MG) were measured by B-mode ultrasound in 26 junior soccer players [mean (SD) age: 16.5 (0.6) years] and 20 control college students [age: 18.5 (0.5) years]. Lower leg circumference and MG muscle thickness were significantly (P < 0.05) greater in the soccer players than in the controls. The percent difference (dominant minus non-dominant legs) in muscle thickness and fascicle length were significantly (P < 0.01) larger in the soccer players than in the controls, but the percent difference in pennation angle was similar between groups. The difference (dominant leg minus non-dominant leg) in muscle thickness was significantly correlated (r = 0.55; P < 0.05) with the difference in muscle fascicle length in the soccer players, but not in the controls (r = 0.18). In conclusion, the preferential use of one limb over another, as seen in junior soccer players, results in a greater difference in muscle thickness between the dominant and non-dominant legs. This difference in muscle size was associated with longer fascicle lengths of the dominant leg. Thus, it appears possible that fascicle length may be further influenced by physical training in dominant legs.

Adolescent↗

The complete DNA sequence of the mitochondrial genome of Physarum polycephalum.

The complete sequence of the mitochondrial DNA (mtDNA) of the true slime mold Physarun polycephalum has been determined. The mtDNA is a circular 62,862-bp molecule with an A+T content of 74.1%. A search with the program BLAST X identified the protein-coding regions. The mitochondrial genome of P. polycephalum was predicted to contain genes coding for 12 known proteins [for three cytochrome c oxidase subunits, apocytochrome b, two F1Fo-ATPase subunits, five NADH dehydrogenase (nad) subunits, and one ribosomal protein], two rRNA genes, and five tRNA genes. However, the predicted ORFs are not all in the same frame, because mitochondrial RNA in P. polycephalum undergoes RNA editing to produce functional RNAs. The nucleotide sequence of an nad7 cDNA showed that 51 nucleotides were inserted at 46 sites in the mRNA. No guide RNA-like sequences were observed in the mtDNA of P. polycephalum. Comparison with reported Physarum mtDNA sequences suggested that sites of RNA editing vary among strains. In the Physarum mtDNA, 20 ORFs of over 300 nucleotides were found and ORFs 14 19 are transcribed.

Amino Acid Sequence↗

Effects of preconditioning on ischemia/reperfusion injury of hepatocytes determined by immediate early gene transcription.

Ischemia reperfusion (I-R) of the liver induces various events leading to cell death (apoptosis) and subsequent cells proliferation. Recent experimental studies have described the protective effect of ischemic preconditioning (IPC) on I-R injury of the liver. However, the mechanisms involved in this protection remain unknown. The protein products of immediate early genes (IEGs) behave as crucial transcriptional regulators not only in apoptosis but also in cell proliferation. Here, we evaluated the effects of IPC on IEG transcription after I-R injury, using a rat liver I-R injury model. Injury to hepatocytes was evaluated by measuring serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) and that to endothelial cells by plasma concentration of hyaluronic acid (HA). The extent of necrosis was evaluated by H&E staining, while cell proliferation and apoptosis were evaluated by proliferating cell nuclear antigen (PCNA) and terminal deoxy(d)-UTP nick end labelling (TUNEL) staining, respectively. Alterations in the transcription of IEGs (c-fos and c-jun) were examined by Northern blotting. Rats subjected to 40-min liver ischemia, preceded by 10-min preconditioning, showed significantly lower AST, ALT, LDH, and HA levels at 6 h after I-R than untreated animals (P < 0.05; n at least 5 rats per group). The percentage of necrotic areas at 24 h after I-R was significantly lower in IPC-treated animals than in the controls. The numbers of apoptotic cells at 24 h after I-R and the numbers of PCNA-positive cells at 24 and 48 h after I-R were significantly lower in IPC-treated rats than in controls. Transcription levels of IEGs were low in IPC-treated rats, particularly c-jun at 1 and 1.5 h after I-R (P < 0.05). Our results indicate that IPC provides a significant protective effect on for liver cells against I-R injury and that its effect is evidenced by a significant decrease in the transcription levels of IEGs following the insult.

Animals↗

Induction of immediate early genes after partial hepatectomy in cholestatic liver.

The protein products of immediate early genes (IEGs) behave as transcriptional regulators and play an important role in the regulation of gene expression associated with liver cell proliferation and apoptosis. The aim of this study was to examine whether the transcription of IEGs was induced by obstructive jaundice during liver regeneration after 70% partial hepatectomy, and to examine their association with animal survival, cell proliferation, and apoptosis. Obstructive jaundice (OJ) was induced in rats by common bile duct ligation (CBDL), and 70% partial hepatectomy was performed 5 days after CBDL (OJ group). Changes in the induction of the IEGs, c-fos and c-jun, were compared between control and OJ groups in relation to survival before and after partial hepatectomy. Cell proliferation and apoptosis were evaluated by proliferating cell nuclear antigen (PCNA) immunohistological staining and by an in situ TdT-mediated d-UTP-digoxigerin nick-end labeling (TUNEL) method. The 2-week survival in the OJ group (2/7) was significantly less that of the sham operation (control) group (7/7). Enhanced induction of IEGs was evident in the OJ group after partial hepatectomy compared with findings in the control group. The PCNA-labeling index (LI) in the OJ group was increased after partial hepatectomy, but only minimally, compared with that in control animals. Apoptotic cells appeared in bile ducts and surrounding hepatocytes after partial hepatectomy in the OJ group, although apoptotic cells were rare in the control group. IEG transcription does occur after partial hepatectomy in jaundiced liver but it is enhanced and sustained, and leads to apoptosis rather than leading to the efficient proliferation of hepatocytes.

Animals↗

A reoperation for anomalous origin of right pulmonary artery: report of a case.

A reoperation to upsize the conduit placed at infancy for the repair of an anomalous origin of the right pulmonary artery (AORPA) was successfully performed in an 8-year-old girl because of an elevated right ventricular pressure and a reduced right pulmonary blood flow. Although primary direct anastomosis is essential for AORPA, one should not hesitate to perform a conduit repair (interposition with a tube prosthesis) on an infant with AORPA whose right pulmonary artery is distant from the main pulmonary artery, because a reoperation can safely be performed even in cases where the conduit is relatively narrow as the patient grows. This is the first report of a reoperation, including a complete replacement of the conduit, after an initial conduit repair for AORPA.

Anastomosis, Surgical↗

Traction-type heart stabilizer for off-pump coronary bypass grafting.

We designed a stabilizer to assist us in performing coronary artery bypass grafting on the beating heart. The stabilizer consists of a U-shaped holed platform, an articulating arm, and a clamp for attachment to an ordinary sternal retractor. The target coronary artery is dissected, then two elastic sutures, 15-20mm apart, are wrapped around it, proximal and distal to the anastomotic site. These sutures for traction are passed through holes in the U-shaped platform and tied. This traction immobilizes the target area of the coronary artery. The stabilizer described herein provides good exposure and steady immobilization to enable anastmosis to be more easily performed in the beating heart.

Anastomosis, Surgical↗

Cholesterol granuloma in the petrous apex: case report and review.

Cholesterol granuloma in the petrous apex presents with various symptoms of cranial nerve dysfunction, so the selection for surgical treatment remains controversial. We report a 41-year-old woman with a cholesterol granuloma at the left petrous apex, which was totally resected via a combined middle fossa and posterior transpetrosal approach. In a review of 92 cases, including our case, treated for petrous apex cholesterol granuloma between 1990 and 2001, 38 were men (41.3%) and 54 were women (58.7%). The mean age of these patients was 37.4 years (males were 35.2 years, females were 39.4 years). The most common presenting clinical symptom was hearing loss due to dysfunction of cranial nerve VIII. Seventy-nine patients, including our case, underwent operation, and 13 patients were managed without surgery. The most frequently selected surgical approach was middle cranial fossa approach. Revision surgery (including the 2 cases who underwent revision twice and three times) was performed in 12 patients (15.2%). In 92 cases, all of those who underwent total removal have not shown re-accumulation of cyst contents. On the other hand, 11.4% of the patients with or without permanent drainage route proceeded by subtotal removal of the cyst wall needed revision surgery because of stenosis of the drainage route. Therefore we conclude that the most important treatment for the prevention of re-accumulation of cyst contents may be the extent of the cyst wall resection rather than the establishment of permanent drainage route.

Adolescent↗

Endoscopic transnasal approach to the pituitary lesions using navigation system (InstaTrak System).

Endoscopic transnasal approach has become a procedure of choice for the surgical management of pituitary lesions. However, in conventional endoscopic transnasal surgery, the surgeon may become disorientated to the actual operating position. In our series, 47 patients have undergone an endoscopic transnasal approach to the pituitary with the use of the navigation system called InstaTrak for real-time imaging. This image guidance system proved valuable for anatomical localization during pituitary surgery. We have reduced the average surgical time, and improved patient outcome. As a consequence, complications during surgery should decrease and safety should increase. Intra-operative image guidance is expected to have major advantageous effects on pituitary surgery by allowing the surgeon to remove lesions more efficiently. As this system is improved technically and surgeons become more proficient in their use, there should be better postoperative outcomes.

Humans↗

Comparative analysis of host responses related to immunosuppression between measles patients and vaccine recipients with live attenuated measles vaccines.

Measles virus infection induces a profound immunosuppression. We analyzed in a time-dependent manner peripheral bloods of one to two-year-old children immunized with live attenuated measles vaccines, compared with age-matched measles patients, for immunosuppression. In contrast to transient severe lymphopenia with measles patients, primarily due to extensive apoptosis of a broad spectrum of uninfected lymphocytes, neither apoptosis nor lymphopenia occurred with measles vaccine recipients. Increase in number and activation of NK cells, which might compensate for the lymphopenia in measles patients, were not found with the vaccinees. While cell surface expression of apoptosis-related molecules such as TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-receptors, CD95(Fas) and Fas-ligand, and plasma interferon-gamma were increased for measles patients, they remained unchanged after vaccination. Plasma interleukin (IL)-18, which is responsible for inducing apoptosis in several infectious diseases, was increased predominantly with measles patients, whereas the increase remained marginal with the vaccinees. IL-10 was elevated transiently in both measles patients and vaccinees. Decrease in plasma IL-12, which is often correlated with T cell suppression, was not found for both cases. Serum IgM and IgG antibodies to measles virus were induced at lower titers in the vaccinees than measles patients. These results indicate that in contrast to wild-type measles virus, live measles vaccines hardly provoked host cytokine responses that lead to apoptotic cytolysis of uninfected lymphocytes, lymphopenia and immunosuppression, and thereby induced weaker immune responses to the virus.

Antibodies, Viral↗