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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 181 records · Page 10Linked to original sources
PubMed2000

Leptin receptor and leukemia.

The receptor for leptin, the gene product of the obese gene, is expressed in hematopoietic stem cells. Leptin stimulates normal myeloid and erythroid development, and is secreted from bone marrow adipocytes, which occupy most of the marrow cavity in humans. Leptin might thus play an important role in the control of the expansion and differentiation of primitive hematopoietic cells through paracrine interaction in the bone marrow microenvironment. Leukemic cells of some patients with acute myeloblastic leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia (CML) also express the leptin receptor. In cases of CML, higher expression of leptin receptor is observed during blast crisis than in chronic phase. Leptin alone and in combination with other cytokines has stimulative effects on proliferation of leukemia cells as well as anti-apoptotic effects. These findings suggest the possibility that leptin plays roles in the pathophysiology of leukemia.

Carrier Proteins↗
PubMed2000

Amantadine-induced multiple spike waves on an electroencephalogram of a schizophrenic patient.

Although amantadine is relatively free of side effects compared with levodopa, the incidence and severity of unwanted effects, such as hallucinations, insomnia and dizziness, markedly increase when the daily dose exceeds 200 mg. A 63-year-old schizophrenic female developed the Pisa syndrome following neuroleptic medication. She was started on a regimen of amantadine, 200 mg per day, on September 4, and the electroencephalogram (EEG) on September 11 was within normal limits. The dosage was increased to 300 mg on September 18 because there was no improvement and no side effects. Two days later a generalised convulsion occurred and an EEG revealed frequent multiple spikes or sharp waves with slow waves. No epileptic seizure has been observed since the amantadine was discontinued. The EEG on September 27 was again within normal limits. To our knowledge, the EEG of a patient with convulsion induced by amantadine has not been described previously. The epileptic mechanisms of amantadine have not been elucidated; however, it may be related to a modulating role of dopamine in the central nervous system.

Amantadine↗
PubMed2000

[Perioperative management for total en bloc spondylectomy--the effects of preoperative embolization and hypotensive anesthesia].

We retrospectively evaluated the effects of preoperative embolization and hypotensive anesthesia on total en bloc spondylectomy (TES) for solitary spinal metastases. In ten patients (treatment group), feeding arteries of spinal metastases were embolized preoperatively and controlled hypotensive anesthesia was induced during operation. In other ten patients (control group), these treatments were not applied. Intraoperative blood loss as well as the amount of blood transfused in the treatment group were significantly lower than those in the control group. Moreover, postoperative platelet counts in the treatment group were significantly higher than those in the control group. These findings indicate that embolization of feeding arteries of metastases and hypotensive anesthesia decrease intraoperative blood loss and may prevent postoperative complications in TES.

Aged↗
PubMed2000

Orienting axon growth: spinal nerve segmentation and surround-repulsion.

The study of spinal nerve trajectories in higher vertebrate embryos has revealed an inherent polarity within somites along the antero-posterior axis, and provides a simple system in which to study the factors that influence axon pathfinding. We argue that the orientation of spinal axons is determined by the simultaneous operation of two distinct guidance mechanisms, contact repulsion and chemorepulsion. Motor and sensory axons traverse the anterior half of each somite because they are excluded by contact repulsion from the posterior half-somite, and the molecular nature of several candidate contact repellents is reviewed. In contrast, we find that the dorsoventral trajectory of primary sensory axons is oriented by diffusible repellents originating from the notochord medially and dermamyotome laterally. In this system, therefore, repulsion by surrounding tissues ('surround-repulsion') is the main force directing axon growth in three dimensions.

Animals↗
PubMed2000

[Surrogate and true endpoints in cancer clinical trials].

To facilitate the proper and quick evaluation of cancer chemotherapy, the issues of surrogate and true endpoints in clinical trials were reviewed. Surrogate endpoints are defined as response variables that can substitute for a true endpoint due to their close correlation with the true endpoint, and their occurrence earlier than true endpoint. The response rate in cancer chemotherapy has been used as a surrogate or true endpoint for the evaluation of treatments. However, recent studies revealed that response rates do not always correlate with survival time (time to failure), and better surrogate endpoints such as time to progression, median survival time, or various surrogate biomarkers are now under investigation.

Chemoprevention↗
PubMed2000

Co-transduction of herpes simplex virus thymidine kinase gene and human interleukin-2 gene into mouse ovarian cancer cell line, OVHM.

We studied the thymidine kinase (TK) gene and the interleukin (IL)-2 gene co-transduction into tumor cells for a possible strategy of cancer gene therapy. A murine ovarian cancer cell line, OVHM, was retrovirally transduced with the TK (OVHM/TK) or the IL-2 gene (OVHM/IL-2). The TK or IL-2 expression was permanent in OVHM/TK or OVHM/IL-2. OVHM/TK cells were susceptible to gancyclovir (GCV) in vitro, and their intraperitoneal growth was completely regulated with GCV administration. The bystander effect was not observed in vitro and in vivo in this model, and only the marginal emergence of immune involvement was observed in the OVHM/TK-cured mice with GCV. OVHM/IL-2 cells produced IL-2 biologically active to be immunogenic, but still tumorigenic to kill the mice when inoculated intraperitoneally. Then, OVHM/TK cells were co-transduced with the IL-2 gene to establish OVHM/TK/IL-2 cells. OVHM/TK/IL-2 cells were also susceptible to GCV and transiently produced active IL-2. A significant resistance against the challenge of parental tumor cells was observed in the mice that were inoculated with OVHM/TK/IL-2 cells and cured with GCV administration. It is suggested that tumor cells transduced with both TK and IL-2 genes could be regressed with GCV administration with subsequent generation of immune activation in the host. Since the bystander effect may not always be a common phenomenon in gene therapy using the TK gene, this type of combination may be advantageous in the clinical application of gene therapy for human cancers.

Animals↗
PubMed2000

IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis.

PURPOSE: To determine the immunosuppressive status of aqueous humor (AqH) from mouse eyes afflicted with endotoxin-induced uveitis (EIU) and to identify the relevant cytokines responsible for immunomodulatory activity within EIU AqH. METHODS: Bacterial lipopolysaccharide (LPS) was injected into hind footpads of C3H/HeN mice; and AqH, collected at 6, 12, 24, and 48 hours, was evaluated for content of transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma and capacity to suppress anti-CD3-driven T-cell proliferation. Cytokine mRNA expression in iris-ciliary body (I/CB) was analyzed by RNase protection assays. RESULTS: During 6 to 24 hours after LPS injection, total TGF-beta levels in AqH increased even though the fluid lost its capacity to suppress T-cell activation. At this time, AqH contained high levels of IL-6, and I/CB contained high levels of IL-6 mRNA. When IL-6 was neutralized with specific antibodies, inflamed AqH reacquired its capacity to suppress T-cell activation, which correlated with high levels of TGF-beta. Coinjection of IL-6 plus antigen into the anterior chamber of the eye of normal mice prevented antigen-specific anterior chamber-associated immune deviation (ACAID). CONCLUSIONS: LPS-induced intraocular inflammation is associated with local production of IL-6, which robs AqH of its immunosuppressive activity, perhaps by antagonizing TGF-beta. The fact that IL-6 antagonized ACAID induction in normal eyes suggests that strategies to suppress the intraocular synthesis of IL-6 may reduce inflammation and restore ocular immune privilege.

Animals↗
PubMed2000

[Diffusion-weighted magnetic resonance imaging of neuro-Behçet's disease].

We report 2 patients (35-year-old and 38-year-old men) with neuro-Behçet's disease and characterize their diffusion-weighted MRI (DWI) findings of brain. T2-weighted and fluid-attenuated inversion recovery images obtained during the acute phase of neurological manifestations demonstrated multiple hyperintense lesions with a characteristic distribution in the brain including brainstem, thalamus, basal ganglia, and cerebral hemisphere. Most of these lesions did not exhibit increased signal intensity on DWI. This MRI profile, especially the combination of isointensity on DWI and hyperintensity on T2-weighted image, of neuro-Behçet's disease is similar to that of multiple sclerosis, and different from that of acute cerebral infarction and herpes simplex encephalitis.

Acute-Phase Reaction↗
PubMed2000

Clinical and analytical evaluation of an enzyme immunoassay for myelin basic protein in cerebrospinal fluid.

BACKGROUND: RIA of myelin basic protein (MBP) in cerebrospinal fluid (CSF) is commonly used as a biochemical marker of demyelination in patients with multiple sclerosis (MS). Our aim was to develop a sufficiently sensitive ELISA for MBP and evaluate it clinically in patients with MS. METHODS: The ELISA used anti-bovine MBP antibody coated on plates and biotinylated anti-MBP antibody. The bound antibody complex was quantified with streptavidin-horseradish peroxidase. MBP was determined in CSF from 84 MS patients and 55 patients with other neurological diseases. RESULTS: The respective within- and between-assay CVs were 4.7% and 7.2% at 200 ng/L, and 6. 3% and 8.8% at 2000 ng/L. The detection limit was 30 ng/L. Most of the MS patients with acute exacerbations had markedly increased MBP in the CSF. Longitudinal studies of six MS patients with recurrent exacerbation confirmed this observation. MBP concentrations from 78 MS patients, as tested with our ELISA, correlated well with those obtained by RIA (r = 0.9; P: <0.01), but the detection limit of the ELISA was much lower than that of the RIA. CONCLUSIONS: This convenient ELISA with higher sensitivity than the existing assays is a suitable routine assay that provides a diagnostic indicator of myelin breakdown in the central nervous system; moreover, it is an excellent indicator of MS disease activity.

Adolescent↗
PubMed2000

Basic and clinical evaluation of a newly-developed enzymatic bilirubin assay.

An enzymatic bilirubin assay using bilirubin oxidase was evaluated. Its repeatability and linearity were excellent, and excellent correlations were observed between the enzyme and the diazo methods in total and conjugated bilirubin. The coefficient of correlation between the conjugated bilirubin fraction obtained with the diazo method and that of HPLC was 0.424, while this coefficient was 0.580 for the diazo method. A multi-laboratory study using 3 serum specimens revealed lower coefficients of variation for the enzymatic method than for the diazo method. Bilirubinuria specimen showed good accord between total bilirubin and conjugate bilirubin levels for the enzymatic method, not for the diazo method. When 12 newborn baby specimens and 34 pediatric specimens were studied, all exhibited increased concentrations of conjugated bilirubin with the diazo method. In an adult case with prolonged jaundice, the diazo method usually yielded higher conjugated bilirubin values than the enzymatic method. The enzymatic method was then concluded to be superior to the diazo method for conjugated bilirubin determination.

Adult↗
PubMed2000

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma].

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.

Adolescent↗
PubMed2000

[Total hematological analysis system as a screening test for hematological malignancy].

Measurement of complete blood cell count and white blood cell differentiation is an essential laboratory test and the most important screening test for hematological malignancy. Recently, several automated blood cell analyzers have been developed to improve accuracy and precision. When flag messages generated in the presence of morphological abnormalities of the samples are displayed, manual revision is necessary. In our laboratory, the manual revision rate has been 35-40%. Therefore blood cell analyzers are useful in screening for abnormalities as well as greatly reducing expensive and time-consuming manual differential procedures. In addition, automated blood cell analyzers can provide several types of useful information including the leukocyte distribution scattergram. However, most such information is not utilized in the clinical field. In the future, a total hematological analysis system will be constructed so that all information provided by automated blood cell analyzer and by manual methods are available.

Blood Cell Count↗
PubMed2000

[Mycosis fungoides terminating in acute myelocytic leukemia].

A 57-year-old woman was admitted to our hospital with suspected leukemia in September 1999. In 1990, systemic erythema had occurred, and mycosis fungoides (MF) had been diagnosed by skin biopsy. Interferon-gamma therapy had not been effective, and the erythema had disappeared after treatment with psoralen and ultraviolet A (PUVA) therapy (1.46 J/cm2). The patient had subsequently done well with a course of topical steroids. On admission this time, the WBC count was 1,600/microliter with 6% blasts. The total nucleated cell count in a bone marrow aspirate was 43.1 x 10(4)/microliter, of which 86.2% were peroxidase-positive blasts. Acute myelocytic leukemia (AML) was diagnosed. Chromosomal analysis demonstrated abnormalities of 48, XX, +4, +8, +add(10)(p11), add(11)(q23) in 10 of 20 cells, and 51, idem, +6, +8, +21, +mar in 8 cells with mixed-lineage leukemia gene rearrangement. Therapies (radiation, chemotherapy and PUVA) for MF, and the altered immune response seen in patients with this disease, especially in the more advanced stages, collectively termed cutaneous T-cell lymphoma (CTCL), suggest that such patients may be at increased risk of a second primary malignancy. To our knowledge, AML has been reported in 8 MF patients including the present one. Attention should be given to the possibility of MF terminating in AML.

Female↗
PubMed2000

[Problems in measurement of forced vital capacity--quality assessment with extrapolated volume].

In 1994, the American Thoracic Society proposed criteria for the start of expiration, middle of expiration and end of expiration in order to improve the accuracy of forced vital capacity measurement. Extrapolated volume (EV) and percent extrapolated volume (%EV), which serve as the criteria for the start of expiration, were studied in this paper. It was demonstrated that the values of %V50 and %FEV1.0% increased incorrectly when EV or %EV were outside the criteria because of an erroneous start point for expiration or poor technique. Similar results were obtained in the same subjects, who underwent FVC measurement more than twice with different effort levels. The present study demonstrated that obstructive ventilatory impairment may be underestimated if EV or %EV is outside the criteria. We concluded that the values of EV and %EV are parameters which indicate a rapid rise of the internal pressure of the thoracic cavity at the start of expiration and should be considered in seeking correct measurement of respiratory function including FVC.

Adult↗
PubMed2000

[Relation between serum eosinophil cationic protein (ECP) level and asthma attack in children].

Serum eosinophil cationic protein (sECP) levels were measured in 339 patients with childhood asthma, and the clinical courses of these patients were followed for 57 weeks. While considering the history and characteristics of each patient, we examined the correlation between asthma attack frequency and sECP, blood eosinophil count, and serum total IgE (tIgE) to determine their usefulness in predicting asthma attacks. Among patients with no other allergic diseases, sECP levels in patients who had no asthma attacks two weeks before or after the measurement were significantly lower than those of patients who had attacks during the same four-week period. Among patients who had attacks, those patients with no attack for a year after the measurement were also found to have low sECP levels. Similarly, even among patients with asthma attacks and high sECP levels, there were cases where attacks were well controlled using nebulizer treatments with DSCG or BDP. The incident rate of attacks for patients with other allergic diseases and a low sECP was low. Yet, there was no common trend in patients with high sECP levels. Moreover, this study detected a significant correlation between sECP level and blood eosinophil count as well as between sECP level and serum tIgE. The most significant correlation with asthma attack frequency was sECP level. Thus, sECP level seems to reflect the allergy activity level, especially two weeks prior to and after the measurement. For patients without other allergic diseases, asthma attack prediction during the two weeks period after the measurement of sECP also seems possible. Therefore, periodic measurement of sECP level is useful in objectively monitoring the improvement of symptoms and establishing the treatment plan, including treatment with DSCG or BDP.

Adolescent↗
PubMed2000

[B precursor lymphoblastic leukemia/lymphoma manifested at onset as hemophagocytic syndrome].

A 20 year-old male patient was admitted to our department for the treatment of recurrence of fever and pancytopenia developed despite of temporal remission of hemophagocytosis syndrome that had been treated with large doses of methylprednisolone in our hospital. Superficial lymph nodes were not palpable. CT scan and echography revealed neither findings of splenohepatomegalia or enlargement of intraabdominal lymph nodes. Bone marrow aspiration showed an increase of histiocytes, the cells phagocytizing erythrocytes and platelets, and a negative test for peroxidase stain. Analysis of surface antigens showed that 11.3% of cells were blast cells positive for CD10, CD19, CD20, CD34 and TdT. Bone marrow biopsy revealed a localized increase in tumor cells positive for L26, CD10 and negative for UCHL-1. Because of the absence of detectable tumor masses and the difficulty in differentiating between malignant lymphoma and lymphatic leukemia, we diagnosed the condition as B precursor lymphoblastic leukemia/lymphoma. If diagnosed with malignant lymphoma preceded by hemophagocytic syndrome(LAHS), he might have a rare type of LAHS-associated malignant lymphoma since histological examination did not reveal diffuse large cell lymphoma, a condition found in most patients with LAHS-associated malignant lymphoma. Whereas if diagnosed as ALL, he was the first adult patient with ALL with HPS at onset as far as we know. In any of these possibilities, the case was considered rare.

Adult↗
PubMed1999

An event-related potential study in schizophrenia using Japanese sentences.

To examine the neurophysiological and cognitive characteristics of language disorder in schizophrenia, the N400 component and late positive component (LPC) of event-related potentials (ERPs) were investigated in medicated schizophrenic patients and health comparison subjects. The subjects were required to indicate whether Japanese sentence completions were semantically congruous or incongruous. The ERPs for the range of 300-500 ms to the incongruous completions contained a more negative component (N400), followed by LPC, which was inversely more positive for the incongruous than congruous condition. The N400 effect and the mean amplitude of the LPC were reduced in the patients. The attenuated N400 effect in schizophrenics mainly originated from an enhanced negativity for the congruous completions, suggesting that the use of context is poor in schizophrenia.

Adult↗