Biomedical subjects

K Nibu

Publications and source records attributed to K Nibu.

At least 19 recordsLinked to original sources

PubMed2001

Mechanical properties of the human cervical spine as shown by three-dimensional load-displacement curves.

STUDY DESIGN: The mechanical properties of multilevel human cervical spines were investigated by applying pure rotational moments to each specimen and measuring multidirectional intervertebral motions. OBJECTIVES: To document intervertebral main and coupled motions of the cervical spine in the form of load-displacement curves. SUMMARY OF BACKGROUND DATA: Although a number of in vivo and in vitro studies have attempted to delineate normal movement patterns of the cervical spine, none has explored the complexity of the whole cervical spine as a three-dimensional structure. METHODS: Sixteen human cadaveric specimens (C0-C7) were used for this study. Pure rotational moments of flexion-extension, bilateral axial torque, and bilateral lateral bending were applied using a specially designed loading fixture. The resulting intervertebral motions were recorded using stereophotogrammetry and depicted as a series of load-displacement curves. RESULTS: The resulting load-displacement curves were found to be nonlinear, and both rotation and translation motions were coupled with main motions. With flexion-extension moment loading, the greatest degree of flexion occurred at C1-C2 (12.3 degrees), whereas the greatest degree of extension was observed at C0-C1 (20.2 degrees). With axial moment loading, rotation at C1-C2 was the largest recorded (56.7 degrees). With lateral bending moments, the average range of motion for all vertebral levels was 7.9 degrees. CONCLUSIONS: The findings of the present study are relevant to the clinical practice of examining motions of the cervical spine in three dimensions and to the understanding of spinal trauma and degenerative diseases.

Analysis of Variance↗

PubMed2001

Expression of NeuroD and TrkB in developing and aged mouse olfactory epithelium.

To better understand the roles of NeuroD, a member of the basic helix-loop-helix transcription factor family, during the differentiation of olfactory receptor neurons, we studied the expression of NeuroD in developing and aging mouse olfactory epithelium (OE). During embryonic period, NeuroD expression is confined in the basal compartment of OE. During neonatal period, NeuroD expression is detected in the middle compartment and in the basal compartment of OE. In the adult, the number of NeuroD expressing cells in the basal compartment significantly decreased, while the NeuroD-positive cells in the middle compartment was maintained throughout lifetime. This dual phase expression pattern of NeuroD suggests multiple roles of NeuroD in the neurogenesis of ORNs.

Aging↗

PubMed2001

Identification of dual specificity phosphatases induced by olfactory bulbectomy in rat olfactory neuroepithelium.

Dual specificity protein tyrosine phosphatases (dsPTPs) are a subfamily of protein tyrosine phosphatases implicated in the regulation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 mitogen-activated protein kinases (MAPKs) which are target enzymes activated by a wide range of cell-surface stimuli. Like these kinases, a class of dsPTP has been implicated in cell differentiation, regeneration, and apoptosis. In order to isolate dsPTPs which might play an important role in neuronal regeneration and apoptosis in olfactory neuroepithelium, we subcloned DNA fragments amplified by reverse transcription-polymerase chain reaction (RT-PCR), using degenerate oligonucleotide primers based on the conserved amino acid regions within the catalytic domain of dsPTPs, from rat olfactory epithelial RNA 1 and 4 h after an olfactory bulbectomy. The PCR products were subcloned into the pCRII vector, and 23 clones were chosen for further characterization. The sequence of these 23 individual clones revealed that two clones were identical to the rat dsPTP, MKP-3, and the other 21 clones were identical to the rat dsPTP, MKP-1. By Northern analysis, the MKP-1 transcript was induced and peaked 4 h following a bulbectomy. Similar results were obtained with the MKP-3 transcript. These results suggest that MKP-1 and MKP-3 may be involved in the early steps of apoptosis in vivo in rat olfactory neuroepithelium.

Animals↗

PubMed2001

Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

Adolescent↗

PubMed2001

Metastasis of cervical esophageal carcinoma to the temporal bone--a study of the temporal bone histology.

A 49-year-old male developed left abducens nerve palsy as a result of metastatic spread of carcinoma of the cervical esophagus to Rouviere's node and infiltration of the petrous portion of the left temporal bone. Postmortem temporal bone histology revealed that cancer cells had invaded the greater superficial petrosal nerve (GPN), lesser superficial petrosal nerve, tensor tympani muscle (TTM) and the skin covering the anterior wall of the left external auditory meatus. These findings suggest that the carcinoma metastasized from the cervical esophagus to Rouviere's node and directly invaded the middle cranial fossa and then the temporal bone, and further infiltrated the middle ear via perineural invasion.

Carcinoma, Squamous Cell↗

PubMed2000

bFGF induces differentiation and death of olfactory neuroblastoma cells.

Olfactory neuroblastoma (ONB) is a highly vascularized and malignant tumor arising in olfactory neuronal precursors from the paranasal sinuses. Previously, we showed that treatment of JFEN cells with transforming growth factor (TGF)-alpha caused them to differentiate and respond to chemical odorants, whereas basic fibroblast growth factor (bFGF) treated cells differentiated and died. In the present study we show that established ONB tumors treated with bFGF upregulate the bFGF receptor (FGFR1) prior to differentiation. This cellular differentiation was evidenced by bFGF-induced expression of the human runt homologue AML1 (PEBP2 alpha B, CBFA-2) that is highly expressed in developing olfactory neuroepithelium and TrkA, a preferred nerve growth factor receptor. Since TrkA is expressed in supporting cells, but not in mature olfactory neurons, we hypothesize that the expression of AML1 and TrkA in bFGF-treated JFEN cells induced supporting cell differentiation. Collectively, these results have implications for the treatment of patients afflicted with ONB.

Animals↗

PubMed2000

Potassium-adsorption filter for RBC transfusion: a phase III clinical trial.

BACKGROUND: Within the past 2 years, three cases of cardiac arrest just after rapid transfusion of RBCs preserved for over 7 days after 15-Gy irradiation were found. This severe complication caused transient hyperkalemia. To prevent potassium (K(+)) overload by RBC transfusion at the bedside, a K(+)-adsorption filter made of sodium polystyrene sulfonate was developed. STUDY DESIGN AND METHODS: After in vitro and animal safety and efficacy tests, a Phase III clinical trial was conducted with 65 patients given transfusions via the newly developed filter (filter group) and 37 patients in whom the filter was not used (control group) and transfusions were given at twice the usual flow rate (20 mL/min). RESULTS: More than 85-percent (94.4+/-3.8%) removal of K(+) in RBCs in mannitol-adenine-phosphate (MAP) that had been preserved for more than 14 days or that were used 3 days after 15-Gy irradiation (calculated K(+): 3.8+/-1.3 mEq/bag) was achieved in 82 of 83 bags of MAP RBCs in the filter group, with 79.6 percent removed in the other, even in rapid transfusions. RBC recovery 1 day after transfusion, determined by increments in RBCs, Hb, and Hct, were 24 and 0.4 x 10(4) per microL, 0.7 and 0.3 g per dL, and 1.6 and 0 percent, respectively, in the filter and control groups. No adverse transfusion reactions, such as hypotension, anaphylactoid reactions, or asthma-like attacks, were observed, except for one case of urticaria in the filter group. Mild fever (within 1 degrees C) after transfusion was observed in both groups. Serologic markers of hemolysis rose slightly in both groups, but there was no significant difference between the two groups. CONCLUSION: The newly developed K(+)-adsorption filter is useful, especially in a rapid transfusion setting.

Adenine↗

PubMed2000

Treatment of childhood acute myelogenous leukemia with allogeneic and autologous stem cell transplantation during the first remission: a report from the Kyushu-Yamaguchi Children's Cancer Study group in Japan.

A total of 64 newly diagnosed acute myelogenous leukemia patients (except FAB M3 and/or Down syndrome) under 18 years of age were consecutively enrolled into the study. Patients having an HLA-identical sibling (allo group) were assigned to undergo allogeneic bone marrow transplantation (allo BMT) in the first complete remission (CR). Others (non-allo group) were assigned to undergo autologous peripheral blood stem cell transplantation (PBSCT) or autologous BMT (auto BMT). Conditioning regimen was busulfan + melphalan for all transplantation. Of 64 patients (allo group 24; non-allo group 40), 59 (92.2%) achieved a CR. Eighteen relapses occurred (allo group 4; non-allo group 14) and 6 died during the first CR. The 5-year event-free survival (EFS) rate was 53.3 +/- 6.4% at a median follow-up period of 45 months. The 5-year EFS rates of allo and non-allo groups were 70.8 +/- 9.3% and 43.0 +/- 8.1%, respectively (p = .08). The EFS rates at 5 years post-transplant for allo BMT from an HLA-identical sibling (n = 18), PBSCT (11), and auto BMT (6) were 88.1 +/- 7.9%, 41.6 +/- 19.7%, and 83.3 +/- 15.2%, respectively. The outcome of allo BMT was superior to that of autograft. Auto BMT rather than PBSCT might contribute to a long-term survival in case of no available HLA-identical siblings.

Adolescent↗

PubMed1999

A G to A transition at the last nucleotide of exon 6 of the gamma c gene (868G-->A) may result in either a splice or missense mutation in patients with X-linked severe combined immunodeficiency.

We report here that a defect of the interleukin common gamma subunit (gamma c) in X-linked severe combined immunodeficiency (XSCID) previously known as a missense mutation resulted instead in exon skipping in a Japanese XSCID patient. The phenotype of the patient was consistent with that of typical XSCID, and his Epstein-Barr virus-transformed B cells accordingly entirely lacked surface expression of gamma c . On analysis by the reverse transcription-polymerase chain reaction (RT-PCR), a single but small gamma c mRNA species was detected. Exon 6, which encodes the transmembrane domain of gamma c, was skipped in the mRNA. A G to A mutation was found at the last nucleotide of exon 6 of the gamma c gene (868G-->A). The predicted consequence of the exon skipping is a frameshift resulting in a premature stop codon, and the mutated gamma c presumably loses association with the cell membrane. In XSCID, this mutation (868G-->A) is known as a missense mutation that results in R285Q [corrected]. Previously reported patients with the same mutation apparently had no aberrant or alternative splicing but did have the R285Q [corrected] exchange. Similar mutations at the last nucleotide of an outskipped exon have been reported. However, such mutations do not always cause exon skipping. Analyses of RNA structural changes induced by the mutations supported the variability of consequences of the mutations. Taken together, our findings suggest that the 868G-->A mutation of the gamma c gene may affect gamma c transcripts differently, i.e., generating missense or exon skipping, in XSCID patients with the same mutation. Patient-specific variation in splicing thus appears to occur.

Adenine↗

PubMed1999

Olfactory neuron-specific expression of NeuroD in mouse and human nasal mucosa.

Human olfactory neuroepithelium (OE) is situated within the olfactory cleft of the nasal cavity and has the characteristic property of continually regenerating neurons during the lifetime of the individual. This regenerative ability of OE provides a unique model for neuronal differentiation, but little is known about the structure and biology of human olfactory mucosa. Thus, to better understand neurogenesis in human OE, we studied the expression of olfactory marker protein (OMP), TrkB and NeuroD in human nasal biopsies and autopsy specimens and compared these data with those obtained from normal and regenerating mouse OE. We show that NeuroD and TrkB are coordinately expressed in human OE. Thus, by using these markers we have been able to extend the known boundaries of the human OE to include the inferior middle turbinate. In normal mouse OE, TrkB and OMP expression overlap in cells closest to the superficial layer, but TrkB is expressed more strongly in the lower region of this layer. In contrast, NeuroD expression is more basally restricted in a region just above the globose basal cells. These characteristic expression patterns of OMP, TrkB and NeuroD were also observed in the regenerating mouse OE induced by axotomy. These results support a role of NeuroD and brain-derived neurotrophic actor (BDNF), the preferred ligand for TrkB, in the maintenance of the olfactory neuroepithelium in humans and mice.

Adult↗

PubMed1998

The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids.

Our research goal is to better understand the mechanisms controlling the initiation and progression of thyroid diseases. One such disease, papillary thyroid carcinoma (PTC), is the leading endocrine malignancy in the United States. Recently, a family of related fusion proteins, RET/PTC1-5, has been implicated in the early stages of PTC. Although all five members of this family have the c-RET proto-oncogene kinase domain in their COOH terminus, little is known about how these genes alter follicular cell biology. Consequently, to answer questions related to the mechanism of the RET/PTC fusion protein action, we have devised a molecular genetic strategy to study PTC using a mouse model of thyroid disease. A new member of this fusion oncogene family, RET/PTC3, which has been implicated in more cases of solid tumor carcinoma (79%) than PTC1 or PTC2 and predominates (80%) in radiation-induced thyroid cancer of children, was investigated in our study. We have generated transgenic mice expressing human RET/PTC3 exclusively in the thyroid. These mice develop thyroid hyperplasia, solid tumor variants of papillary carcinoma and metastatic cancer. This new transgenic line will be useful in deciphering the molecular and biological mechanisms that cause PTC and histological variations in humans.

Animals↗

PubMed1998

Deregulated expression of TCL1 causes T cell leukemia in mice.

The TCL1 oncogene on human chromosome 14q32.1 is involved in the development of T cell leukemia in humans. These leukemias are classified either as T prolymphocytic leukemias, which occur very late in life, or as T chronic lymphocytic leukemias, which often arise in patients with ataxia telangiectasia (AT) at a young age. The TCL1 oncogene is activated in these leukemias by juxtaposition to the alpha or beta locus of the T cell receptor, caused by chromosomal translocations t(14:14)(q11:q32), t(7:14)(q35:q32), or by inversions inv(14)(q11:q32). To show that transcriptional alteration of TCL1 is causally involved in the generation of T cell neoplasia we have generated transgenic mice that carry the TCL1 gene under the transcriptional control of the p56(lck) promoter element. The lck-TCL1 transgenic mice developed mature T cell leukemias after a long latency period. Younger mice presented preleukemic T cell expansions expressing TCL1, and leukemias developed only at an older age. The phenotype of the murine leukemias is CD4-CD8+, in contrast to human leukemias, which are predominantly CD4+CD8-. These studies demonstrate that transcriptional activation of the TCL1 protooncogene can cause malignant transformation of T lymphocytes, indicating the role of TCL1 in the initiation of malignant transformation in T prolymphocytic leukemias and T chronic lymphocytic leukemias.

Animals↗

PubMed1998

Simulation of whiplash trauma using whole cervical spine specimens.

STUDY DESIGN: Whiplash injuries were studied in an experiment using whole cervical spine specimen. OBJECTIVES: To develop a whiplash trauma model that uses a whole cervical spine specimen, and to show the feasibility and unique features of such a model. SUMMARY OF BACKGROUND DATA: Whiplash trauma has been simulated in biomechanical experiments using volunteers, whole body cadavers, animals, anthropometric dummies, and mathematic models. These experiments require large facilities, are expensive, and provide limited information about cervical spine injuries. METHODS: An alternate approach, in which a bench-top sled accelerating apparatus is used to produce whiplash trauma, has been developed to study such trauma in whole cervical spine specimens. Several transducers were developed to monitor soft tissue injuries during the trauma. The model also provides quantification of injuries to the cervical spine. RESULTS: To assess the feasibility and usefulness of the model, a specimen was traumatized, and the following parameters were monitored during the trauma: linear acceleration of the sled, linear and angular acceleration of the head surrogate, displacements of the head surrogate, loads at T1 and C1 vertebrae, and linear deformations of capsular ligaments and vertebral artery. CONCLUSIONS: This model, which incorporates a fresh cadaveric whole human cervical spine specimen, can simulate whiplash trauma effectively and is useful in providing a comprehensive set of clinically relevant information during the trauma. This model gives insight into the complex events and interactions that cause the injuries that occur during whiplash trauma.

Cadaver↗

PubMed1998

[Biomechanics of whiplash injury].

The article reports a new hypothesis of whiplash injury based on a series of experimental studies using isolated human cadaveric specimens. Although the clinical symptoms of whiplash are widely known, the understanding of the underlying injury mechanism is poor. The prevailing view of neck-hyper-extension as the essential injury mechanisms was not supported by recent experiments. In a series of experiments using eight human cadaveric specimens which underwent experimental stepwise whiplash acceleration from 2.5 to 10.5 g functional radiographs and flexibility tests were performed at the end of each acceleration step. Ligament strains, vertebral alignment and elongation of the vertebral artery were monitored during the whiplash trauma by highspeed cinematography and specially designed transducers. After the trauma CT- and MRI-scans were taken and specimens were sectioned using Cryomicrotomy. We found a distinct biphasic kinematic response of the cervical spine to whiplash trauma. In the first phase the spine formed an S-shaped curve with flexion at the upper levels and hyper-extension at the lower levels. This phase was found to be the vulnerable phase of whiplash trauma. The largest dynamic elongation of the capsular ligaments was observed at the C6-C7 level during this initial S-shaped phase of whiplash. The maximum elongation of the vertebral artery could be observed synchronously in the first S-shaped curve of the cervical spine. In the second phase of whiplash all levels of the cervical spine were extended, so that the head reached is maximum extension. No injuries were observed in the second phase. We propose, based on our experimental findings, that with low accelerations the anterior structures of the lower cervical spine are injured during the first phase of whiplash, when the cervical spine forms an S-shaped curve and before the neck is fully extended. At higher trauma accelerations there is also a tendency for the injuries to occur at upper levels of the cervical spine. Based on our findings the traditional view of whiplash as hyper-extension injury can be modified by a differentiated, time dependent, biphasic biomechanical model of the injury, thus allowing better and more effective injury prevention, diagnosis and therapy.

Biomechanical Phenomena↗

PubMed1998

Analysis of tumor recurrence following anterior skull base surgery.

In order to elucidate the predictive factors for tumor recurrence following skull base surgery and the significance of salvage surgery in cases of recurrence, we retrospectively surveyed the incidence, site, and time of local recurrences in 20 patients who underwent either anterior or anterolateral skull base surgery for malignant tumors invading the anterior cranial fossa between 1989 and 1995 at the University of Tokyo Hospital. Nineteen patients underwent total resections of malignancies, with recurrences and/or metastases occurring in 13. Local recurrences occurred at the skull base in 5 patients (group A), outside the skull base in 4 patients (group B), and in both locations in 2 patients (group C). The mean time interval between surgery and recurrence was 29 months in group A, and 4.2 months in groups B and C. The local recurrence-free rates were 51% at 1 year and 34% at 5 years. Both brain and/or dural invasion and a microscopic positive surgical margin were proven to be predictive factors for tumor recurrences. The 3-year local recurrence-free rate was 20% in patients with dural invasions and 83% in those without. The incidence of recurrence-free patients was 79% in cases with negative margins, with no patient being recurrence-free in positive cases. All recurrences found more than 6 months after the initial surgery resulted in patients being salvaged successfully by a second operation.

Adolescent↗

PubMed1998

Intervertebral disc distraction with a laparoscopic anterior spinal fusion system.

The BAK spinal fusion system has been applied to laparoscopic anterior lumbar interbody fusion. The system, consisting of a pair of cylindrical implants with threads, placed symmetrically about the sagittal plane, functions by tensioning the annulus fibrosis. Cylindrical plugs of increasing size are inserted prior to the implant placement. As the procedure may affect spinal posture and disc height, we measured changes due to incremental plug insertion using human cadaveric spine specimens (L5-S1, n = 4). Multi-directional flexibility of the construct was also measured as a function of plug size. The disc height change was found to increase initially and then to level off at 13-mm diameter plugs. In the sagittal plane, the intervertebral posture first shifted towards kyphotic then came back to the initial lordotic posture with plugs of bigger size. However, changes in disc height and spine posture were not statistically significant. Comparing the neutral zone (NZ) flexibility after inserting the plugs to the intact values, neither the flexion/extension nor the axial rotation NZ showed any significant change. In lateral bending, the NZ decreased after the insertion of 13-mm plugs (p < 0.05). Insertion of plugs of increasing size from 9 mm to 12 mm decreased the range of motion (ROM) in all directions (p < 0.05). Insertion of 13-mm and 14-mm plugs decreased the flexion/extension and lateral bending ROM, but not the axial rotation ROM, probably indicating some injury to the annulus fibers.

Adult↗

PubMed1998

Whiplash injuries and the potential for mechanical instability.

Whiplash injury to the cervical spine is poorly understood. Symptoms often do not correlate to the clinical findings. It has been hypothesized that the long-term clinical symptoms associated with whiplash have their basis in mechanical derangement of the cervical spine caused at the time of trauma. Before such a hypothesis can be proven, one needs to document and quantify the soft tissue injuries of the cervical spine in whiplash. The purpose of the study was to quantify the mechanical changes that occur in the cervical spine specimen as a result of experimental whiplash trauma. Utilizing a whiplash trauma model, injuries to human cadaveric cervical spine specimens (C0-T1 or C0-C7) were produced by increasingly severe traumas. The flexibility tests determined the motion changes at each intervertebral level in response to 1.0 Nm pure flexion-extension moment. Parameters of range of motion (ROM) and neutral zone (NZ) were determined before and after each trauma. Significant flexibility increases first occurred in the lower cervical spine after 4.5-g rear-end (anteriorly directed) acceleration of the T1 vertebra. At this acceleration magnitude, extension ROM and NZ at C5-C6 increased (P < 0.05) by 98% and 160% respectively. There was also a tendency (P < 0. 1) for the extension NZ at C0-C1 and C6-C7 levels to increase after the 6.5-g acceleration by 52% and 241% respectively. There were no such tendencies for the ROM parameter. We have identified the threshold and sites of whiplash injury to the cervical spine. This information should help the clinician make more precise diagnoses in the case of whiplash trauma patients.

Cadaver↗

PubMed1998

Dumbbell type jugular foramen meningioma extending both into the posterior cranial fossa and into the parapharyngeal space: report of 2 cases with vascular reconstruction.

Two cases with huge dumbbell type jugular foramen meningioma with extension into the parapharyngeal space are reported. A well co-ordinated surgical strategy for total resection to this high risk tumour with neurosurgeons, otolaryngologists and plastic surgeons is mandatory to minimise operative complications. Both of our patients presented with a cervical mass and lower cranial nerve palsies, and had huge dumbbell type masses extending from the posterior cranial fossa through the jugular foramen to the parapharyngeal space, encasing the cervical internal carotid artery. Gross total resection of the tumours was successfully achieved by basically a 2-stage operation. In the first stage, posterior fossa tumours were removed by the transjugular approach, combined with the petrosal approach in one case. In the second stage, cervical tumours were removed along with the cervical carotid artery by the transcervical and/or transmandibular approach, followed by vascular reconstruction from the ipsilateral carotid artery to the middle cerebral artery using saphenous vein graft. From these experiences, we recommend this 2-stage operation for large dumbbell type meningiomas extending to the infratemporal/parapharyngeal space. The intracranial tumour is removed at the first operation. The extracranial portion is resected at the second, and if necessary, the involved cervical carotid artery is resected and simultaneous revascularisation using saphenous vein graft is performed with a vascularised free muscle graft. This strategy could maximise the functional preservation on the one hand, and minimise the surgical risk, such as postoperative infection, on the other.

Adult↗