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H Takeshima

Publications and source records attributed to H Takeshima.

At least 55 records · Page 3Linked to original sources
PubMed2000

Junctophilins: a novel family of junctional membrane complex proteins.

Junctional complexes between the plasma membrane (PM) and endoplasmic/sarcoplasmic reticulum (ER/ SR) are a common feature of all excitable cell types and mediate cross-talk between cell surface and intracellular ion channels. We have identified the junctophilins (JPs), a novel conserved family of proteins that are components of the junctional complexes. JPs are composed of a carboxy-terminal hydrophobic segment spanning the ER/SR membrane and a remaining cytoplasmic domain that shows specific affinity for the PM. In mouse, there are at least three JP subtypes: JP-1, -2, and -3. JP-2 is abundantly expressed in the heart, and mutant mice lacking JP-2 exhibited embryonic lethality. Cardiac myocytes from the mutant mice showed deficiency of the junctional membrane complexes and abnormal Ca2+ transients. Our results suggest that JPs are important components of junctional membrane complexes.

Amino Acid Motifs↗
PubMed2000

Randomized comparison of intra-arterial versus intravenous infusion of ACNU for newly diagnosed patients with glioblastoma.

This prospective randomized trial was performed to compare the effectiveness of intra-arterial ACNU with intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. The primary end points were overall survival and progression-free survival. Within 3 weeks after surgery, patients were randomly assigned to receive either intravenous or intra-arterial ACNU (80 mg/m2) once every 6 weeks concomitant with radiotherapy. Intraarterial ACNU was administered for the first 3 courses followed by intravenous administration. Eighty-four patients were enrolled onto this study and among them 82 patients who passed eligibility criteria were analyzed. Patients characteristics were not different significantly between 2 treatment arms. Median survival and progression-free survival time was 59 and 24 weeks, respectively for intra-arterial arm and 56 and 45 weeks, respectively for intravenous arm. There was no significant difference respectively between two treatment arms. Among the prognostic variables including age, Karnofsky performance status, extent of surgery and treatment arm, Cox's proportional hazards model showed that age was the only significant factor for both survival and progression-free survival (P = 0.003 and 0.016, respectively). With regard to toxicity, there was no significant difference between two treatment arms. Leukoencephalopathy was not observed in intra-arterial arm. In conclusion, intra-arterial ACNU when administered by the method in this study does not increase the survival and progression-free survival of newly diagnosed patients with glioblastoma over that afforded by intravenous ACNU.

Adolescent↗
PubMed2000

A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer: a prospective study.

BACKGROUND: A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. METHODS: Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. Intra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. RESULTS: Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. CONCLUSIONS: This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function.

Aged↗
PubMed2000

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer.

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.

Adult↗
PubMed2000

Screening for prostate cancer using prostate-specific antigen alone as a first-line checkup parameter: results of the health checkup system.

BACKGROUND: The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS: Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS: Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS: These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

Aged↗
PubMed2000

Effects of graded levels of dietary casein and corn oil on total cholesterol and triacylglycerol in plasma and liver of rats.

With the intention of examining the effects of dietary protein and oil levels on total cholesterol (T-CHOL) and triacylglycerol (TG) concentrations in the plasma and liver, male Wistar rats, weighing about 170 g, were fed diets containing graded levels of casein and corn oil for 2 wk. At the 5, 20, and 30% levels of dietary corn oil, plasma T-CHOL concentrations were generally enhanced in proportion to the rise of dietary casein level, but plasma TG contents were scarcely influenced by the level. At the 8 to 35% casein levels, plasma T-CHOL and TG concentrations were the highest at the 5% corn oil level, followed in order by the 20 and 30% levels of oil. At the 5 and 20% oil levels, hepatic T-CHOL contents were hardly changed at the 8 to 30% casein levels, but enhanced at the 35% casein level. At the 30% oil level, the T-CHOL contents tended to be changed proportionally to casein levels. At all levels of casein, hepatic T-CHOL contents tended to be relatively high at the 30% corn oil, middle at the 20% oil, and low at the 5% one. At each corn oil level, TG contents in the liver tended to be elevated at the 8 to 15% casein levels and highly preserved at the 15 to 25% ones. Then, the raised TG contents declined at the 5 and 20% levels of corn oil and remained constant at the 30% oil. At each casein level, the contents of hepatic TG were generally high at the 30% oil level, followed in order by the 20 and 5% oil levels. These results indicated that plasma and liver T-CHOL concentrations were proportionately enhnaced by the increase in casein level, and plasma TG contents were hardly affected by the level and hepatic TG ones were lowered by relatively lower or higher casein level, and the rise in corn oil level generally reduced plasma T-CHOL and TG concentrations, but raised hepatic ones.

Animals↗
PubMed2000

Suppression of the tissue factor-dependent coagulation cascade: a contributing factor for the development of intratumoral hemorrhage in glioblastoma.

To clarify factors that may contribute to the development of intratumoral hemorrhage, we analyzed the expression of tissue factor (TF), an initiator of the extrinsic coagulation pathway, and of tissue factor pathway inhibitor (TFPI) in glioblastomas with or without massive intratumoral hematoma. Among 196 glioma cases reviewed, there were 13 with macroscopic intratumoral hemorrhage. We focused on the glioblastomas and used immunoblot- and immunohistochemical methods to compare the expression of TF and TFPI in 9 glioblastomas with macroscopic hematoma and 30 glioblastomas without macroscopic hemorrhage. Although TF was expressed in most glioblastomas irrespective of the presence or absence of macroscopic hemorrhage, the staining patterns differed significantly: TF-positive glioma cells were diffusely present in the non-hemorrhage group; in the group with hemorrhage, positive cells, primarily macrophages, were scattered throughout the tissue examined. The expression of TFPI was significantly higher in the group with than in the group without hemorrhage. Our results suggest that local suppression of the TF-dependent coagulation cascade is a contributing factor that permits the occurrence of intratumoral hemorrhage.

Adult↗
PubMed2000

Gene delivery with optimized electroporation parameters shows potential for treatment of gliomas.

Electroporation, a standard laboratory method of introducing exogenous molecules into cells, has been gaining importance as a very effective non-viral physical technique of gene delivery. In this study, we have used subcutaneous model of the C6 rat glioma cells and established an optimal condition to obtain very high gene expression in tumor tissues using both reporter and functional genes. Tumors grown on the flanks of Wistar rats are exposed and directly injected with plasmid DNA having the constructs of luciferase, green fluorescent protein and, the fragment of the diphtheria toxin, DT-A. The tumors are then subjected to square wave pulses from an electroporator. Gene expression is found to be several orders of magnitude higher when the tumors are pulsed with the optimized electrical parameters compared to the controls. For luciferase, the enhancement is approximately 135-fold, for the green fluorescent protein, gene expression is seen over a wide area within the sections examined, as contrast to a few punctate dots in the control specimens, and finally, DT-A shows massive death in the tumor tissue. A special circular array of six needles through which pulses are delivered with rotating electric field is found to be highly efficient in transferring genes inside the tumor. Direct injection of plasmid DNA followed by electroporation allows very high in vivo gene transfer and its subsequent expression into tumor tissues. This method may be applicable to any solid tumor.

Animals↗
PubMed2000

[Intrascrotal tumors: a clinicopathologic study of 15 cases].

PURPOSE: We reviewed cases of intrascrotal tumors treated at our institution except for germ cell testicular tumors. PATIENTS AND METHODS: From 1977 to 1998 (22 years), 120 cases of intrascrotal tumors treated at the University of Tsukuba. Of these, 15 cases (12.5%) were not germ cell testicular tumors. The patients' ages varied between 2 and 77 years with a mean of 49.6. RESULTS: The most common complaint regarding symptoms was painless testicular enlargement. Tumor weight ranged from 2 to 200 g, with an average of 104.6 g. The histological diagnoses of 15 patients were 8 malignant lymphomas, 2 paratesticular rhabdomyosarcomas, 2 metastatic tumors (origin; stomach and prostate), 1 epidermoid cyst, 1 cyst of tunica testis, and 1 adenomatoid tumor. As for the cases with malignant lymphoma, all of them were non-Hodgkin's lymphoma whose clinical stages were stage I in 2 cases and stage IV in 6 cases. Five 8 patients died in spite of systemic chemotherapy after an orchiectomy, whereas 2 cases with metastatic tumors died of primary cancer, and two cases with paratesticular rhabdomyosarcoma are still alive and have had no evidence of disease. CONCLUSIONS: Intrascrotal tumors except for germ cell testicular tumors are not common, and consist of various diseases. In particular, some kinds of malignant lymphoma mimic anaplastic seminoma histopathologically. Therefore, accurate diagnosis and precise treatment is important in the patient with intrascrotal tumors.

Adolescent↗
PubMed2000

Spinal seeding of anaplastic ependymoma mimicking fungal meningitis. A case report and review of the literature.

BACKGROUND: The spinal seeding from brain tumors sometimes mimicks fungal meningitis on examination of cerebrospinal fluid. METHODS AND RESULTS: A 19-year-old woman gradually developed increased intracranial hypertension. MRI identified a mass in the right parieto-occipital area. It was totally removed and histologically diagnosed as an anaplastic ependymoma. Radiation- and chemotherapy were administered postoperatively. The patient reported low back pain 5 months after the surgical treatment. MRI disclosed neither spinal dissemination nor tumor recurrence at the primary site. Lumbar puncture was performed and the cerebrospinal fluid (CSF) was found to have an extremely low glucose level (5 mg/dl); no tumor cells were identified. Blood samples were obtained and a relative increase of WBC and CRP was noted. A slight degree of inflammation and low-grade fever were recorded. A tentative diagnosis of fungal meningitis was made and anti-fungal therapy was administered transventricularly and transvenously. However, her neurological condition continued to deteriorate gradually. Sequential CSF studies showed that the glucose level remained extremely low, it even decreased to 0 mg/dl Eight months after the surgical treatment, MRI with Gd-DTPA revealed marked subarachnoid enhancement in both intracranial and spinal areas. An open biopsy was performed and a histological diagnosis of intracranial and spinal seeding of the anaplastic ependymoma was returned. CONCLUSIONS: We report a patient with intracranial and spinal seeding of an anaplastic ependymoma that mimicked fungal meningitis. We discuss the difficulty of obtaining a differential diagnosis in this case and describe the mechanism of the decreased CSF glucose level.

Adult↗
PubMed2000

[Lipoma].

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Humans↗
PubMed1999

Abnormal features in skeletal muscle from mice lacking mitsugumin29.

Physiological roles of the members of the synaptophysin family, carrying four transmembrane segments and being basically distributed on intracellular membranes including synaptic vesicles, have not been established yet. Recently, mitsugumin29 (MG29) was identified as a novel member of the synaptophysin family from skeletal muscle. MG29 is expressed in the junctional membrane complex between the cell surface transverse (T) tubule and the sarcoplasmic reticulum (SR), called the triad junction, where the depolarization signal is converted to Ca(2+) release from the SR. In this study, we examined biological functions of MG29 by generating knockout mice. The MG29-deficient mice exhibited normal health and reproduction but were slightly reduced in body weight. Ultrastructural abnormalities of the membranes around the triad junction were detected in skeletal muscle from the mutant mice, i.e., swollen T tubules, irregular SR structures, and partial misformation of triad junctions. In the mutant muscle, apparently normal tetanus tension was observed, whereas twitch tension was significantly reduced. Moreover, the mutant muscle showed faster decrease of twitch tension under Ca(2+)-free conditions. The morphological and functional abnormalities of the mutant muscle seem to be related to each other and indicate that MG29 is essential for both refinement of the membrane structures and effective excitation-contraction coupling in the skeletal muscle triad junction. Our results further imply a role of MG29 as a synaptophysin family member in the accurate formation of junctional complexes between the cell surface and intracellular membranes.

Amino Acid Sequence↗
PubMed1999

Involvement of ryanodine receptor type 3 in dopamine release from the striatum: evidence from mutant mice lacking this receptor.

Although it is known that ryanodine receptor type 3 is expressed in the striatum, the function of this receptor has not been elucidated. Therefore, we examined whether caffeine- and ryanodine-induced dopamine release in striatal slices is affected in mice lacking ryanodine receptor type 3. Pretreatment with thapsigargin, an inhibitor of the Ca(2+) ATPase pump of the endoplasmic reticulum, abolished caffeine- or ryanodine-induced dopamine release in slices from normal mice. Dopamine concentration in the striatum and KCl-induced dopamine release were unaffected by a ryanodine receptor type 3 deficiency. Ryanodine-induced dopamine release was significantly attenuated in mice lacking ryanodine receptor type 3, whereas caffeine-induced dopamine release was partially attenuated. Caffeine produced a similar hyper-motor activity in both wild and homozygous mice. The present results suggest the involvement of ryanodine receptor type 3 in dopamine release from the striatum.

Animals↗
PubMed1999

Expression of citrulline-nitric oxide cycle in lipopolysaccharide and cytokine-stimulated rat astroglioma C6 cells.

Nitric oxide (NO) is involved in many physiological and pathological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS), with citrulline generated as a by-product of the reaction. Thus, citrulline can by recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) via the citrulline-NO cycle. Rat astroglioma C6 cells were treated with bacterial lipopolysaccharide (LPS), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha, and the expression of the enzymes of the citrulline-NO cycle was investigated by RNA blot and immunoblot analyses. NO production from arginine and citrulline was also assessed. iNOS mRNA and protein were induced 6-12 h after stimulation with LPS and cytokines and decreased at 24 h. AS mRNA increased up to 12 h and decreased at 24 h. AS protein increased gradually up to 48 h. On the other hand, AL mRNA remained unchanged by stimulation. NO production from arginine was enhanced by the treatment with LPS and cytokines. NO production was also observed when arginine was replaced by citrulline. These results indicate that NO production is enhanced in LPS- and cytokine-stimulated C6 cells due to induction of iNOS and that the citrulline-arginine recycling is important for NO production.

Animals↗
PubMed1999

A negatively charged region of the skeletal muscle ryanodine receptor is involved in Ca(2+)-dependent regulation of the Ca(2+) release channel.

The ryanodine receptor/Ca(2+) release channels from skeletal (RyR1) and cardiac (RyR2) muscle cells exhibit different inactivation profiles by cytosolic Ca(2+). D3 is one of the divergent regions between RyR1 (amino acids (aa) 1872-1923) and RyR2 (aa 1852-1890) and may contain putative binding site(s) for Ca(2+)-dependent inactivation of RyR. To test this possibility, we have deleted the D3 region from RyR1 (DeltaD3-RyR1), residues 1038-3355 from RyR2 (Delta(1038-3355)-RyR2) and inserted the skeletal D3 into Delta(1038-3355)-RyR2 to generate sD3-RyR2. The channels formed by DeltaD3-RyR1 and Delta(1038-3355)-RyR2 are resistant to inactivation by mM [Ca(2+)], whereas the chimeric sD3-RyR2 channel exhibits significant inactivation at mM [Ca(2+)]. The DeltaD3-RyR1 channel retains its sensitivity to activation by caffeine, but is resistant to inactivation by Mg(2+). The data suggest that the skeletal D3 region is involved in the Ca(2+)-dependent regulation of the RyR1 channel.

Amino Acid Sequence↗
PubMed1999

Tissue factor expressed in pituitary adenoma cells contributes to the development of vascular events in pituitary adenomas.

BACKGROUND: Tissue factor (TF) was initially identified as an important factor in the initiation of coagulation. TF has recently been found to be expressed highly in certain types of malignant tumors. It has also been reported to be involved in systemic coagulopathy in cancer patients and in the proliferative and invasive activities of tumor cells. Tissue factor pathway inhibitor (TFPI) is a strong biologic inhibitor of TF. To the authors' knowledge, this is the first study of the expression of TF and TFPI in human pituitary adenoma. METHODS: The expression of TF and TFPI were analyzed by immunohistochemical methods in human pituitary adenoma samples. To examine whether TF and TFPI expression influence the proliferative and/or invasive character of pituitary adenomas, the authors determined the MIB-1 labeling indices and invasiveness of all the pituitary adenomas they examined. Furthermore, to determine whether TF contributes to coagulation inside adenoma tissues, the incidence of cysts or hematomas in adenomas was analyzed. RESULTS: In cells from 29 of 83 pituitary adenomas, overexpression of TF was observed. This was not the case for normal pituitary gland cells. TFPI was not expressed in either the adenomas or the normal pituitary glands from adenoma-bearing individuals. The expression of TF was significantly correlated with the formation of cysts or hematomas in pituitary adenomas. However, no such correlation with either the proliferative activity or the invasive character of the adenomas was observed. CONCLUSIONS: Locally overexpressed TF in adenoma cells may contribute to the development of vascular events, such as infarction and/or hemorrhagic infarction, in pituitary adenomas.

Adenoma↗