Biomedical subjects

T Fukushima

Publications and source records attributed to T Fukushima.

At least 109 records · Page 6Linked to original sources

PubMed2000

Differentiation induction in non-lymphocytic leukemia cells upon treatment with mycophenolate mofetil.

Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U937 leukemic cells as well as in fresh leukemia cells from patients with non-lymphocytic leukemia. Treatment with mycophenolate mofetil reduced the intracellular guanosine 5'-triphosphate (GTP) levels and induced morphologic and functional differentiation in HL-60 and U937 cells dose-dependently. HL-60 and U937 cells developed macrophage-like cytoplasm as well as the expression of CD11b and CD14 antigens and the ability to oxidize nitroblue tetrazorium (NBT). These changes became evident when the intracellular GTP levels decreased to approximately 20-30% of the untreated control level and were abrogated by the addition of guanosine. In the fresh leukemic cells, differentiation induction was shown in the cells derived from seven of 13 patients. The fresh leukemia cells responding to mycophenolate mofetil revealed significant higher positivity to CD11b, CD14, and NBT before treatment and significantly reduced intracellular GTP levels after treatment compared to the non-responding cells. These findings suggest that mycophenolate mofetil induces differentiation in HL-60 and U937 cells and some fresh leukemia cells with moderate tendency to maturation, by causing a decrease in the intracellular GTP levels. Mycophenolate mofetil could be a promising differentiation inducer in vivo.

Adult↗

PubMed2000

Effect of PSC 833 on the cytotoxicity and pharmacodynamics of mitoxantrone in multidrug-resistant K562 cells.

We examined the effect of PSC 833, a nonimmunosuppressive cyclosporin analogue, on the cytotoxicity, accumulation and retention of an anthraquinone antileukemia drug mitoxantrone (MIT). This was done in P-glycoprotein (PGP)-overexpressing multidrug-resistant K562/D1-9 cells and compared with the effect of cyclosporin A (CsA). We also compared MIT with the effect of PSC 833 on the cytotoxicity of daunorubicin (DNR) and doxorubicin (DOX). While PSC 833 and CsA had no effect on the cytotoxicity, accumulation and retention of MIT in the parent K562 cells, PSC 833 and CsA restored accumulation and retention of MIT in K562/D1-9 cells dose-dependently. Consequently, there was increased sensitivity of K562/D1-9 cells to MIT. The reversing activity of PSC 833 on the cytotoxicity of MIT was stronger than that of CsA, and was almost the same as the reversing activity of PSC 833 on the cytotoxicity of DNR and DOX. The resistance index of MIT decreased from 43.9-fold to 2.8-fold by 0.4 microM PSC 833, which is a clinically achievable plasma concentration. These results suggest that the combination of PSC 833 with MIT could be a promising treatment in reversing PGP-mediated MDR in leukemia patients.

Antineoplastic Agents↗

PubMed2000

Pre- and postoperative bone metabolism of primary hyperparathyroidism.

UNLABELLED: Primary hyperparathyroidism (PHPT) is a well-known indicator of severe bone loss. However, the recovery process of bone mineral density after surgery in PHPT patients is not sufficiently clear. We examined postoperative bone metabolism in 24 PHPT patients. PATIENTS AND METHODS: Subjects were 24 patients with PHPT upon whom we performed parathyroidectomy in the Department of Surgery II, Fukushima Medical University. Mean age was 54.2 years and the male-to-female ratio was 10:14; mean time of follow-up was 27.3 months. Patients were divided histopathologically into 16 adenomas and eight hyperplasias, and classified by heredity into seven familial (six, MEN 1; one, MEN 2) and 17 sporadic types. Bone mineral density was measured by dual energy X-ray absorptometry (DXA) and digital image processing (DIP). Age-matched values of these parameters were obtained. Serum bone metabolic parameters; ionized calcium (CaF), phosphorus, intact PTH (iPTH), c-PTH, ALP, osteocalcin (OC) and PTHrP were measured. RESULTS: PHPT patient preoperative bone mineral densities were significantly lower than those of healthy controls. Those by DIP method were lower than those by DXA. High CaF, iPTH, OC and ALP levels were indicated before surgery, but all parameters immediately became normal. Longitudinal bone mineral density changes of asymptomatic cases increased more than those of patients with renal stone and/or ostitis fibrosa. In adenoma cases, tumor weights were significantly inversely, which correlated with preoperative DIP bone density measurements. CONCLUSION: Preoperative PHPT patients showed decreased bone density; bone loss in symptomatic cases was especially prominent compared to asymptomatic cases. Most PHPT patients had not completed the BMD recovery after surgery, so even asymptomatic and mild PHPT patients should undergo parathyroidectomy to minimize irreversible bone loss.

Absorptiometry, Photon↗

PubMed2000

Allogeneic bone marrow transplantation improves the outcome of de novo AML with trilineage dysplasia (AML-TLD).

De novo acute myeloid leukemia (AML) with dysplastic features in erythroblasts, granulocytes and megakaryocytes, similar to those in myelodysplastic syndrome (MDS) has been described as AML with trilineage dysplasia (AML-TLD) since 1987. Several reports have suggested that AML-TLD is a subtype of de novo AML in adults and has a poor clinical outcome when treated by conventional chemotherapy. It is not certain whether allogeneic bone marrow transplantation (BMT) brings a favorable outcome for AML-TLD. To evaluate the therapeutic efficacy of allogeneic BMT for AML-TLD, we investigated the clinical data and outcomes of conventional chemotherapy and allogeneic BMT for 118 patients with de novo AML. These patients were registered consecutively for the Japan Adult Leukemia Study Group (JALSG) protocols at our institutes. We treated 28 AML-TLD patients and 90 AML-nonTLD patients with conventional chemotherapeutic protocols. AML-TLD patients did not have a significantly different complete remission (CR) rate (75.0% and 88.4% P = 0.1234), but had a significantly higher relapse rate than AML-nonTLD patients (94.1% and 49.3%, P= 0.0007). The outcome of chemotherapy for AML-TLD was significantly worse than that for AML-nonTLD. The overall survival (OS) and leukemia-free survival (LFS) at 6 years were 9.4% and 0% in AML-TLD group, and 51.9% (P= 0.0017) and 46.3% (P< 0.0001) in AML-nonTLD group, respectively. Meanwhile, among the patients who underwent allogeneic BMT, five of eight AML-TLD patients and eight of 14 AML-nonTLD patients were alive, and three and five patients survived more than 3 years, respectively. These results suggest that allogeneic BMT can improve the outcome for AML-TLD, which is poor when conventional chemotherapy is given alone. Allogeneic BMT before relapse may be the best therapeutic strategy for AML-TLD patients under 50 years of age if a donor is available.

Adolescent↗

PubMed2000

Primary leiomyosarcoma of the cervical spine causing spontaneous compression fracture: report of an autopsy case.

An extremely rare case of the primary leiomyosarcoma of the cervical spine presenting as a compression fracture is reported. A 69-year-old man complained of dysesthesia of both hands. A plain radiograph, computed tomography and magnetic resonance imaging of the cervical spine showed a compression fracture of the vertebral body at C7 without the formation of an obvious mass. From radiological findings, the fracture was considered to be caused by an infiltrative vertebral bone tumor. Biopsy of the tumor revealed a leiomyosarcoma, a metastatic tumor being ruled out by a systemic investigation. The patient died of pleural metastasis 6 months later, and an autopsy confirmed the primary site of the tumor as the cervical spine.

Aged↗

PubMed2000

Delayed resolution of intracranial germinoma after radiotherapy: a preliminary study of the correlation between histology and magnetic resonance imaging.

A central nervous system germinoma is curable in most cases by radiotherapy, and most of the tumor mass disappears promptly after 20-30 doses. However, some germinomas take a longer period to vanish completely from magnetic resonance imaging (MRI) or computed tomography (CT) scans. In such cases, the tumor may contain components such as teratoma. The aim of this study was to clarify the nature of the persistence of some germinomas. Five cases of histologically verified germinoma in which radiotherapy was performed to treat residual tumor were selected. The doses of focal radiotherapy and whole brain radiotherapy were 10-20 Gy and 20-34 Gy, respectively. In these cases, correlation was made between the degree of persistence of the tumor when assessed by MRI and the amount of interstitial content, as determined by histology. The histological evaluation, using hematoxylin-eosin stain, silver impregnation and Azan staining was carried out independently of clinical information. The tumor vanished soon after radiotherapy in three cases, but 3-15 months passed before the tumor completely vanished from the MRI scans in the other two cases. The histology of the cases in which the tumor disappeared rapidly was predominantly of large tumor cells and only small amounts of reticulin. However, in the persistent tumors, large amounts of reticulin and vascular components were present. Thus, it is proposed that tumors with a large parenchymal component disappear soon after radiotherapy, whereas tumors composed mainly of interstitial component persist. Long-standing enhancement seen on MRI or CT scans of patients with an intracranial germinoma is indicative of a large amount of interstitial component in the tumor.

Adolescent↗

PubMed2000

Minimally invasive surgical exposure of the extreme high cervical internal carotid artery: anatomical study.

The purpose of this study is to investigate a minimally invasive access to a high cervical lesion involving the internal carotid artery. Using 13 fixed cadaveric preparations, we sought to design a surgical approach that would cause minimal involvement of the surrounding structures and maximal exposure to the extreme high cervical area. This technique preserves the function and integrity of the mandible, sternocleidomastoid, posterior belly of digastric and styloid process muscles. The method uses retraction and mobilisation of those muscles, as well as decompression of the facial from the stylomastoid foramen. The internal carotid artery is exposed up to the entry point into the carotid canal. The cranial nerves IX, X, XI and XII are kept in sight up to the jugular foramen. This approach creates a wide corridor into the deep high cervical and inferior cranial base area and can be utilised for high cervical carotid lesions and tumours related to the artery.

Aged↗

PubMed2000

Accessing the Orbital Roof via an Eyelid Incision: The Transpalpebral Approach.

THIS ARTICLE OUTLINES A NEW SURGICAL TECHNIQUE FOR ACCESSING THE ORBITAL ROOF: the transpalpebral approach. It involves making an incision on the double fold of the upper eyelid, then dissecting the orbital septum and the orbicular muscle of the eye. This exposes the orbital roof and enables the surgeon to approach without a coronal incision of the scalp; the direct eyelid incision provides adequate workspace. We use this approach in three orbital roof fractures and one orbital hemangioma. This orbital approach offers a simpler surgical technique, a less invasive one, and still provides excellent exposure of the superior orbital cavity.

Journal Article↗

PubMed2000

A review of facial nerve outcome in 100 consecutive cases of acoustic tumor surgery.

OBJECTIVE: To determine the facial nerve outcomes at a tertiary neurotological referral center specializing in acoustic neuroma and skull base surgery. STUDY DESIGN: Retrospective review of 100 consecutive patients in whom acoustic neuromas were removed using all of the standard surgical approaches. METHODS: Functional facial nerve outcomes were independently assessed using the House-Brackmann facial nerve grading system. RESULTS: The tumors were categorized as small, medium, large, and giant. If one excludes the three patients with preoperative facial palsies, 100% of the small tumors, 98.6% of the medium tumors, 100% of the large tumors, and 71% of the giant tumors had facial nerve function grade I-II/VI after surgery. CONCLUSION: Facial nerve results from alternative nonsurgical treatments must be compared with facial nerve outcomes from experienced surgical centers. Based on the facial nerve outcomes from our 100 consecutive patients, microsurgical resection remains the preferred treatment modality for acoustic tumors.

Facial Nerve↗

PubMed2000

Dural repair using acellular human dermis: experience with 200 cases: technique assessment.

OBJECTIVE: Many craniotomies require a watertight dural closure. When primary dural repair is not possible, a graft is necessary. Autograft material is not always easily accessible or available, necessitating the use of other material. We performed 200 craniotomies using an acellular human dermal graft (AlloDerm; LifeCell Corp., The Woodlands, TX) to determine its suitability as a dural substitute. METHODS: From June 1996 through March 1998, all patients at Allegheny General Hospital who required a dural substitute graft and in whom autograft harvest was impractical or impossible received the acellular dermal autograft. The running suture technique was used to form a watertight seal. RESULTS: After follow-up for a minimum of 1 year, seven patients have required subsequent surgery. Three patients developed cerebrospinal fluid leaks that were repaired without removing the dermal graft. Four patients developed wound infections that required debridement. In each patient, the graft seemed to be uninvolved in the infectious process and was left in place. The patients were administered antibiotics postoperatively, and there have been no recurrent infections. No adhesion formation or scarring was noted around or underneath the graft in any patient. CONCLUSION: AlloDerm is a reasonable alternative to the available dural graft materials. Its handling characteristics are similar to those of dura, it is biologically inert, and it does not produce adhesion formation.

Biological Dressings↗

PubMed2000

Topography of the vestibulocochlear nerve.

OBJECTIVE: The terms superior vestibular nerve and inferior vestibular nerve have been used in the field of neurosurgery to indicate anatomically the two respective vestibular components of the vestibulocochlear nerve. To reappraise the aptness of this terminology, fascicular patterns and the anatomic relationship of the vestibular and cochlear components were examined. METHODS: Twenty vestibulocochlear nerve specimens were obtained from cadavers. The nerves were excised, with care taken to sustain their spatial relationships, then embedded in paraffin blocks and cross sectioned in 10-microm-thick slices. Serial cross sections were stained and examined with a light microscope. RESULTS: The vestibular component was separated into two parts only at the lateral fundus of the internal auditory canal, lateral to the vestibular ganglion. In the internal auditory canal of all specimens, the vestibular component was represented by numerous fascicles. Around the porus acusticus, the fascicular pattern among the specimens was diverse: 13 of the 20 specimens were still polyfascicular, 4 specimens consisted of two large, distinct fascicles, and, in the remaining 3 specimens, a portion of the vestibular fascicles had fused with the cochlear component. Near the root entry zone, all vestibular fascicles fused and merged with the cochlear nerve to form a single trunk. CONCLUSION: There was no evidence to support the anatomic correctness of specifying the superior and inferior vestibular nerves, except in the lateral fundus of the internal auditory canal.

Brain Stem↗

PubMed2000

Surgical approaches for the treatment of aneurysms on the P2 segment of the posterior cerebral artery.

OBJECTIVE: The P2 segment of the posterior cerebral artery has remained a challenging region to expose surgically. We establish a surgical strategy for P2-segment aneurysms. METHODS: Each segment of the posterior cerebral artery was classified according to Zeal and Rhoton's classification. Fourteen of 18 P2-segment aneurysms were surgically treated. The patient's outcome, the aneurysm location, and the surgical procedures were evaluated. A cadaveric study was performed to clarify the surgical view obtained via three different surgical approaches. RESULTS: Nine aneurysms were clipped, two were trapped, one was coated, and one was excised with parent artery reconstruction. Cerebral revascularization techniques were used for three patients. The pterional approach exposed the anterior half of the P2a segment. The subtemporal approach revealed the P2a segment, but its exposure was restricted by its localization in the ambient cistern. Via the occipital interhemispheric transtentorial approach, the P2p segment was visible and could be manipulated. When the posterior half of P2a segment was high on a coronal view of magnetic resonance imaging, it was extremely hard to access via any approach. CONCLUSION: A surgical strategy for the P2 aneurysm can be planned with accurate prediction of the aneurysm location. When the localization of an aneurysm on the posterior half of P2a segment is high, a resection of brain tissue may be required.

Adolescent↗

PubMed2000

Evolutionary characterization of the six internal genes of H5N1 human influenza A virus.

The entire nucleotide sequences of all six internal genes of six human H5N1 influenza A viruses isolated in Hong Kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2. The presence of previously reported amino acid sequences specific for human strains was confirmed in the PB2, PA, NP and M2 proteins. Nucleotide and amino acid sequence identities of the six internal genes of H5N1 viruses examined here were separated into at least two variant groups. In agreement with the above result, phylogenetic trees of the six internal genes of human H5N1 viruses were generally composed of two minor clades. Additionally, variable dendrogram topologies suggested that reassortment among viruses contributed further to the genetic variability of these viruses. As a result, it became clear that human H5N1 viruses are characterized by divergent gene constellations, suggesting the possible occurrence of genetic reassortment between viruses of the two evolutionary lineages.

DNA-Directed RNA Polymerases↗

PubMed2000

The Rad51 paralog Rad51B promotes homologous recombinational repair.

The highly conserved Saccharomyces cerevisiae Rad51 protein plays a central role in both mitotic and meiotic homologous DNA recombination. Seven members of the Rad51 family have been identified in vertebrate cells, including Rad51, Dmc1, and five Rad51-related proteins referred to as Rad51 paralogs, which share 20 to 30% sequence identity with Rad51. In chicken B lymphocyte DT40 cells, we generated a mutant with RAD51B/RAD51L1, a member of the Rad51 family, knocked out. RAD51B(-/-) cells are viable, although spontaneous chromosomal aberrations kill about 20% of the cells in each cell cycle. Rad51B deficiency impairs homologous recombinational repair (HRR), as measured by targeted integration, sister chromatid exchange, and intragenic recombination at the immunoglobulin locus. RAD51B(-/-) cells are quite sensitive to the cross-linking agents cisplatin and mitomycin C and mildly sensitive to gamma-rays. The formation of damage-induced Rad51 nuclear foci is much reduced in RAD51B(-/-) cells, suggesting that Rad51B promotes the assembly of Rad51 nucleoprotein filaments during HRR. These findings show that Rad51B is important for repairing various types of DNA lesions and maintaining chromosome integrity.

Amino Acid Sequence↗

PubMed2000

Immunohistochemical analysis of the distribution of measles related antigen in the intestinal mucosa in inflammatory bowel disease.

BACKGROUND: Measles virus is implicated in the aetiology of Crohn's disease. This measles hypothesis is mainly supported by immunohistochemical findings that the measles related antigen is present in the intestine of patients with Crohn's disease. Recently we isolated this antigen from the intestine of a patient with Crohn's disease using a molecular cloning technique and produced the monoclonal antibody against it (designated 4F12). AIM: To discover whether the measles related antigen is uniquely present in Crohn's disease. SUBJECTS/METHODS: Colonic mucosa samples from 20 patients with Crohn's disease, 20 with ulcerative colitis, 11 with non-inflammatory bowel disease (IBD) colitis, and nine controls were immunohistochemically stained with the anti-measles monoclonal antibody 4F12. The numbers of positive cells, the ratio of positive cells to nucleated cells, and the staining intensity of the positive cells were compared. Furthermore, the distribution of the measles antigen in other human organs was examined. RESULTS: Both the number of positive cells and the ratio of positive cells to nucleated cells were significantly increased in Crohn's disease, ulcerative colitis, and non-IBD colitis compared with controls (p<0.05) but were similar among the three disease groups. The staining intensity of the positive cells was also similar among the three disease groups. Small numbers of positive cells were observed in the oesophagus, stomach, duodenum, jejunum, and lung. CONCLUSIONS: The presence of the measles related antigen in the colonic mucosa was not unique to Crohn's disease. These results, together with the observation that such a measles related antigen was derived from host protein, do not support the hypothesis that measles virus causes Crohn's disease.

Adolescent↗

PubMed2000

Tuberculin responses and risk of pneumonia in immobile elderly patients.

BACKGROUND: Delayed type hypersensitivity (DTH) response to tuberculin is an important marker of T helper 1 (Th1) mediated acquired immunity against tuberculosis. Depressed DTH responses to tuberculin are observed in immobile elderly individuals with reduced activities of daily living (ADL) scores. Immobility in older people increases the risk of pneumonia related mortality. The decline in the competence of the immune system might be a reason for the increased susceptibility to infection in the elderly and the depressed DTH response to tuberculin might be a predictor for increased risk of pneumonia. METHOD: The DTH responses to tuberculin were examined in 49 older patients with limited ADL of similar severity, all of whom had a past history of positive DTH responses to tuberculin. Responses with an induration diameter of >/=10 mm were considered positive. Reactivities of Th1 and Th2 lymphocytes taken from the peripheral blood of each subject were also examined and compared between the positive tuberculin responders and the negative tuberculin responders. The rates of pneumonia in these groups were then compared prospectively for two years. RESULTS: The number of CD4 lymphocytes differed significantly between patients with a positive tuberculin response (n=22, mean (SE) 1018 (118) x 10(6)/l) and those with a negative response (n=27, 666 (80) x 10(6)/l, p=0.02). Likewise, the number of Th1 cells was significantly higher in positive tuberculin responders than in negative responders (276 (5.8) x 10(6)/l versus 149 (14) x 10(6)/l, p=0.01). However, the numbers of Th2 cells were similar between patients with positive and negative responses (22 (3) x 10(6)/l versus 19 (3) x 10(6)/l, p=0.41). During the follow up period new pneumonia was diagnosed in 18 (67%) of the 27 negative tuberculin responders and in seven (31%) of the 22 positive tuberculin responders. According to the Cox regression model, a hazard ratio of developing pneumonia in patients with a negative tuberculin response compared with those with a positive tuberculin response was 2.57 (95% CI 1.12 to 6.17, p=0.03). CONCLUSION: The diminished DTH response to tuberculin may be a predictor for increased risk of pneumonia in elderly disabled patients.

Aged↗

PubMed2000

Production of LLU-alpha following an oral administration of gamma-tocotrienol or gamma-tocopherol to rats.

An oral administration of gamma-tocotrienol (gamma-T3) or gamma-tocopherol (gamma-Toc) to male rats caused an increase of the concentration of 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxy chroman (LLU-alpha, gamma-CEHC), a natriuretic compound, in plasma with a T(max) of 9 h. The configuration at C-2 of LLU-alpha produced from gamma-T3 or gamma-Toc was assigned as S-form by an HPLC equipped with a chiral column. These data indicated that LLU-alpha was produced not only from gamma-Toc but also gamma-T3, without racemization at C-2 in rats.

Animals↗

PubMed2000

Bone anabolic effects of PTH(1-34) and salmon calcitonin in ovariectomy- and ovariectomy-steroid-induced osteopenic rats: a histomorphometric and biomechanical study.

Using an experimental model of type 1 osteoporosis under the chronic therapy with an anti-inflammatory steroid, the bone anabolic effect of PTH(1-34) was evaluated by histomorphometrical and biomechanical analysis. Wistar female rats (12-week-old) were ovariectomized and allowed to develop an osteopenic model in the presence or absence of methylprednisolone acetate (MPA: 0.1 mg/kg, s.c., 3-days-a-week basis from the 5th week after ovariectomy (OVX)). The osteopenia that developed for the first 12 weeks after OVX was almost completely normalized by subsequent PTH pulsing (20 microg/kg, s.c., 5-days-a-week) for 8 weeks starting at the 13th week; the following characteristics were observed: 1) proximal tibial metaphysis: recovered bone volume, rather increased trabecular thickness and osteoid volume, and normalized eroded surface; 2) 5th lumbar vertebra (L-5): partially recovered trabecular connectivity; 3) femur and 4th lumbar vertebra (L-4): recovered mechanical strength in maximum elastic load and maximum elastic energy. The anabolic effect of PTH(1-34) was not substantially modified by MPA. Salmon calcitonin (SCT: 10 U/kg per day, s.c., 5-days-a-week, for 8 weeks) was anabolic in limited parameters: decreased number of osteoclasts, recovered maximum elastic load in femur, and partially recovered maximum elastic load in L-4. The results suggest that PTH(1-34) pulsing is able to recover OVX-induced osteopenia in the structure and mechanical strength not only of the cancellous bone but also of the cortical bone, and the anabolic effect can be clinically expected even under steroid medication.

Animals↗