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Biomedical subjects

J Takeuchi

Publications and source records attributed to J Takeuchi.

At least 19 recordsLinked to original sources

A case of reversed pituitary dysfunction with intrasellar mass.

Hypopituitarism can be caused by tumor, inflammation, granuloma and injuries. Once pituitary function is disturbed, hormone replacement therapy is necessary for the remaining life span in most cases. We have experienced a rare case of a unique intrasellar mass associated with pituitary dysfunction in which both spontaneously reversed. A 61-yr-old woman developed hypoadrenalism and central diabetes insipidus (cDI). Magnetic resonance (MR) imaging revealed a lobular, strong hypointense lesion with spotty signal in the middle of the hypophysis. This spotty lesion showed isointensity on T1- and high-intensity on T2-weighted MR images. The spotty signal as well as the normal pituitary lobe were enhanced by the administration of gadolinium. As replacement therapies for hypoadrenalism and cDI, 10 mg of hydrocortisone and 2.5 microg of desmopressin acetate were prescribed. Three months later, slight shrinkage of intrasellar mass and spontaneous improvement of pituitary functions were found. Hydrocortisone was then discontinued. Furthermore, because polyuria and polydipsia were improved nine months later, desmopressin acetate was stopped. Currently, the intrasellar mass continues to shrink, and the patient shows no symptoms without medication. Based upon the unique features of MR images, we suspect that the origin of the mass is an intrasellar hemangioma.

Diabetes Insipidus, Neurogenic↗

WT1 expression level and clinical factors in multiple myeloma.

Although Wilm's Tuomor gene (WT1) was first identified as a tumor suppressor gene for Wilm's tumor, WT1 overexpression has been detected in different malignant cell types including leukemia. Increased expression of WT1 in acute leukemia is potentially used as a marker of minimal residual disease. However, the significance of the gene for multiple myeloma is still not clear. To determine the clinical relevance of WT1 expression in multiple myeloma, we examined the association of clinical parameters and WT1 expression in bone marrow for 17 newly diagnosed multiple myeloma patients. WT1 was assessed by real-time quantitative polymerase chain reaction (RQ-PCR) and calculated standardized WT1 expression level per 100 plasma cells in the bone marrow specimen as "corrected WT1". The expression of standardized WT1 and corrected WT1 in myeloma was 59 to 1,600 copies/microg RNA and 0.05 to 406.3 copies/microg RNA/100 plasma cells, respectively, lower than in leukemia. WT1 transcripts increased when clinical factors worsen, including the stage, amount of M protein, Hb, platelet count, blood urea nitrogen (BUN), creatinine, serum alkaline phosphatase (ALP), calcium, beta2-microglobulin, thymidine kinase activity (TK), and C-reactive protein (CRP). In conclusion, the expression level of WT1 could be an additional marker to the standard parameters considered in risk assessment for multiple myeloma.

Biomarkers, Tumor↗

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study.

In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).

Antibiotics, Antineoplastic↗

Marked hypotensive and blood flow-increasing effects of a new lipo-PGE(1) (lipo-AS013) due to vascular wall targeting.

Lipo-AS013 is being developed as an improved formulation of lipo-PGE(1), which is widely used in clinical practice in Japan and some Asian countries. We have previously reported that lipo-AS013, which is a lipid microsphere (LM) preparation of a chemically stable and lipophilic PGE(1) prodrug (AS013, Fig. 1), slowly releases small amounts of the active ingredient (AS013) in human plasma. In the present study, to estimate the vascular wall targeting ability and efficacy of lipo-AS013, we determined the hypotensive and blood flow-increasing effects of lipo-AS013, lipo-PGE(1), PGE(1)CD, and AS013. Lipo-AS013 was found to have longer-lasting hypotensive and blood flow-increasing effects than the other agents. The two LM preparations, lipo-PGE(1) and lipo-AS013, had a markedly stronger effect than PGE(1)CD and AS013 alone, demonstrating the benefit of drug delivery using LM. In spontaneously hypertensive rats (SHR), lipo-AS013 also had a significant hypotensive effect. To confirm vascular wall targeting by lipo-AS013, the localization of PGE(1) in the aorta and neovascular capillaries of rat was investigated by immunostaining. The results indicated that lipo-AS013 was more efficient at delivering the active ingredient (AS013) to the vessel wall. In conclusion, lipo-AS013 could supersede lipo-PGE(1) and PGE(1)CD in clinical use.

Alprostadil↗

Morphological diagnoses of the Japan adult leukemia study group acute myeloid leukemia protocols: central review.

A morphological review system of the Japan Adult Leukemia Study Group has developed from the AML-87 through the AML-92 experience. We reviewed 1427 (90%) of 1592 cases enrolled in the AML-87, -89, or -92 protocols for morphology; 1408 (88%) were eligible. The rate of diagnostic concordance between each institute and the Committee on Morphological Diagnosis ranged from 76% to 80%. Acute myeloid leukemia (AML) subtypes were as follows: AML M0, 27 (2%); M1, 179 (13%); M2, 472 (34%); M3, 358 (25%); M4, 265 (19%); M5, 57 (4%); M6, 39 (3%); and M7, 11 (1%). The reason for the high number of patients with AML M3 is that many M3 patients were enrolled in the AML-92 protocol, which contained all-trans-retinoic acid. AML M0, M6 and M7 belonged to the poor prognostic groups. Auer bodies were found in 284 (53%) of 538 patients who survived significantly longer than those without Auer bodies in AML-87/-89. In AML-92 except for AML M3, 259 (43%) of 602 cases were Auer+ and also showed better survival rates. The survival of patients with >50% myeloperoxidase (MPO)-positive blast cells was better than those with < or =50% MPO+ blast cells in AML-87/-89. This trend was also seen in AML-92 excluding M3. AML with trilineage dysplasia (AML/TLD) is characterized as a subtype of de novo AML that shows morphological dysplasia of mature hematopoietic cells on a background of leukemic blast cells The number of patients with AML/TLD was 89 (16.5%) of 545 patients reviewed in AML-87/-89. AML-92, except for M3, showed a higher rate of patients with TLD (161 cases; 27.6%) because there were no patients with TLD in the AML M3 group. Survival rates for AML/TLD were worse than those for AML/non-TLD in both the AML-87/-89 and -92 protocols. Eighty percent of all cases (793/986) entered in AML-92 were analyzed cytogenetically. Fifty-one cases were not available for karyotyping because of a lack of mitoses or inappropriate preparations. The most frequent karyotype was normal, which accounted for 34.2%. The t(15;17), t(8;21), and inv(16) karyotypes, which are regarded as good risk factors, were 23.8%, 9.2%, and 1.6%, respectively. Abnormal chromosomes 5, 7, t(9;22), and t(6;9) were considered to be poor or intermediate risk factors As a new system of karyotyping begins in the ongoing AML protocol, useful chromosomal data will be obtained in the near future.

Acute Disease↗

Analysis of 20-year follow-up study of LVP regimen for adult acute lymphoblastic leukemia.

In an attempt to develop a new intensive chemotherapy for adults with untreated acute lymphoblastic leukemia (ALL), 3 sequential programs were designed for 62 patients (age range, 15 to 74 years; median age, 32 years) consisting of the LVP-79 (1979-1984, 27 patients), LVP-85 (1984-1986, 14 patients), and LVP-87 (1987-1989, 21 patients) regimens. The influence of clinical and biologic characteristics on the patient outcome was also examined. L-asparaginase (L-asp), vincristine, and prednisolone, defined collectively as LVP, were administered for induction chemotherapy in all protocols. After achieving complete remission (CR), patients underwent 2 years of multi-agent consolidation, intensification, and maintenance therapy consisting of various combinations. No significant differences were noted between the 3 groups regarding CR rate or survival. In total, 47 of 62 patients (75.8%) achieved CR. The median overall survival (OS) and median CR durations were 550 days and 341 days, respectively. Overall, the estimated survival rate at 20 years was 18.1%. The disease-free survival rate at 20 years was 26.2%. According to univariate analysis, the most favorable pretreatment characteristic for achieving CR was age. A younger age (<40 years of age), platelet count >30 x 10(9)/L, having L1 morphology (French-American-British [FAB]classification subtype), female sex, and the absence of chromosomal abnormalities also helped improve survival rate. According to multivariate analysis, presence of Ph chromosome was found to be a major influencing factor for OS. Although higher doses of L-asp were administered than those used in previous studies, the adverse effect of L-asp was rarely identified. Therefore, it should be considered one of the key drugs for treatment of adult ALL. Further strategies still need to be developed to obtain better survival in adult ALL.

Adolescent↗

Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2.

The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.

Animals↗

Age differences in immunohistochemical localizations of large proteoglycan, PG-M/versican, and small proteoglycan, decorin, in the dermis of rats.

Proteoglycans were localized immunohistochemically in the dermis of Donryu rats, using monoclonal antibodies raised against large proteoglycan (PG-M/versican) and small proteoglycan (decorin). The localizations of these proteoglycans in the dermis were compared between young rats (22-day old) and old ones (24 or 30 months of age), and distinct age differences were observed. In the young dermis, PG-M/versican was observed to be abundant in almost all fibroblastic cells (both cytoplasm and cell processes) whose cellularity was very rich compared with the dermis of old rats. Decorin was only faintly visible in the interstitial fibrous elements of young dermis. In the old dermis, however, decorin was distinctly detected on the fibrous elements, which were diffusely distributed as a fibrous network, and likewise PG-M/versican was visible in only a few fibrous elements which seemed to be the fine processes of fibroblastic cells. In the border layer between epidermis and dermis as well as the basal layer surrounding hair follicles, both large and small proteoglycans could be observed in old dermis. Since decorin, which was abundant in old dermis, has been found to have a growth inhibitory effect, it is conceivable that decorin may be one of the Cell Growth Inhibitory Factors in aging as proposed by Tauchi et al. [17, 18].

Aging↗

Effects of sodium hyaluronate on epithelial healing of the vesical mucosa and vesical fibrosis in rabbits with acetic acid induced cystitis.

PURPOSE: To evaluate the effect of sodium hyaluronate on epithelial healing of the vesical mucosa and vesical fibrosis, and clarify the effect of the sodium hyaluronate solution concentration, we administered sodium hyaluronate in the bladder of rabbits with acetic acid induced cystitis. MATERIALS AND METHODS: Sodium hyaluronate at 3 concentrations (0.1%, 0.2% and 0.4%) was injected intravesically into rabbits with cystitis. Seven days after injection the effect of sodium hyaluronate was evaluated by bladder capacity measurement. Furthermore, the epithelial defective region of the mucosal membrane and bladder dry weight were determined and the condition of the epithelial membrane and extent of fibrosis were examined histologically. RESULTS: In all sodium hyaluronate treated groups a significant improvement in bladder capacity was observed compared to controls. In addition, a significant reduction was noted in the area of the epithelial defective region in the groups treated with 0.2% or 0.4% sodium hyaluronate and a significant decrease was noted in bladder dry weight in the group treated with 0.4% sodium hyaluronate. Histological examination revealed accelerated epithelial healing of the vesical mucosa and inhibited vesical fibrosis in the group treated with 0.4% sodium hyaluronate. CONCLUSIONS: Our findings suggest that sodium hyaluronate is effective for promoting epithelial healing of the vesical mucosa and inhibiting vesical fibrosis.

Acetic Acid↗

Brain-stimulation reward thresholds raised by an antisense oligonucleotide for the M5 muscarinic receptor infused near dopamine cells.

Oligonucleotides targeting M5 muscarinic receptor mRNA were infused for 6 d into the ventral tegmental area of freely behaving rats trained to bar-press for lateral hypothalamic stimulation. The bar-pressing rate was determined at a range of frequencies each day to evaluate the effects of infusions on reward. M5 antisense oligonucleotide (oligo) infusions increased the frequency required for bar pressing by 48% over baseline levels, with the largest increases occurring after 4-6 d of infusion. Two control oligos had only slight effects (means of 5 and 11% for missense and sense oligos, respectively). After the infusion, the required frequency shifted back to baseline levels gradually over 1-5 d. Antisense oligo infusions decreased M5 receptors on the ipsilateral, but not the contralateral, side of the ventral tegmentum, as compared with a missense oligo. Therefore, M5 muscarinic receptors associated with mesolimbic dopamine neurons seem to be important in brain-stimulation reward.

Animals↗

Treatment of a biracial child with schizophreniform disorder: cultural formulation.

Over the past several years, the field of psychiatry has shown a higher level of cultural sensitivity and an increasing interest in the role of cultural factors in mental health. This has been notably reflected in the incorporation of cultural considerations, such as an outline for cultural formulation and a glossary of culture-bound syndromes, in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994). This case report is illustrative of the significance of considering cultural elements in diagnosing and treating a psychiatric disorder. It is also the first-known detailed case report on fakamahaki, a culture-bound syndrome from the Kingdom of Tonga. The syndrome is described in a child from the perspective of a child psychiatry fellow. To serve as a teaching case for clinicians in training as well as those in practice, the DSM-IV outline for cultural formulation has been used. This case can be helpful in educating others in the mental health field about the utility of a more comprehensive approach to understanding clients in contrast to the growing trend of very focused approaches.

Adolescent↗

Thioredoxin inhibits tumor necrosis factor- or interleukin-1-induced NF-kappaB activation at a level upstream of NF-kappaB-inducing kinase.

Gene induction by tumor necrosis factor-alpha (TNFalpha) or interleukin-1beta (IL-1beta) is mediated in part by activation of the transcription factor nuclear factor kappaB (NF-kappaB), and requires signal adaptor molecules such as TNF receptor-associated factor (TRAFs). The latter interact with the NF-kappaB-inducing kinase (NIK), which is believed to be part of the IkappaB kinase complex. Although the precise mechanism is to be elucidated, it is well-known that antioxidant treatments inhibit the inflammatory cytokine-induced NF-kappaB activation. Thioredoxin (TRX) is a 12-kDa endogenous protein that regulates various cellular functions by modulating the redox state of proteins, overexpression of this molecule inhibits NF-kappaB activation. To elucidate the roles of TRX in the signal transduction of the cytokines, we investigated the effects of TRX on NF-kappaB activation induced by cytokine treatment or by overexpression of the signaling molecules. Our data show that TRX treatment inhibits NF-kappaB-dependent transcription at the level of downstream of TRAFs and upstream of NIK: TRX inhibited TRAF2-, TRAF5-, and TRAF6-induced NF-kappaB activation but does not inhibit NIK-, IKKalpha-, and MEKK-induced activation. In addition, we show that TRX inhibits NF-kappaB activation in a manner different from that for SAPK (stress activated protein kinase) inhibition.

Acetylcysteine↗

Deep white matter lesions on MRI, and not silent brain infarcts are related to headache and dizziness of non-specific cause in non-stroke Japanese subjects.

OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. METHODS: To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1:78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3:75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. RESULTS: Silent brain infarcts were demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155). CONCLUSION: The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.

Aged↗

[Analysis of pulmonary function in leukemia patients after bone marrow transplantation: effects of prior chemotherapy].

To evaluate the effects of prior chemotherapy on pulmonary function after bone marrow transplantation(BMT), pulmonary function tests were performed prior to and after BMT on 7 acute leukemia (AL) and 13 chronic myelogenous leukemia (CML) patients given with CY (60 mg/kg x 2 days), total body irradiation (3 Gy x 4 days, 10 cGy/min), and CyA plus short-term MTX. No patient had graft-versus-host disease or lung complications. Pulmonary function after BMT did not deteriorate in the AL patients; however, both %Vital Capacity(%VC) and DL/VA decreased significantly in the CML patients (%VC before BMT: 112.1 +/- 11.5%, after BMT: 93.7 +/- 9.4%; DL/VA before BMT: 79.2 +/- 14.6%, after BMT: 54.1 +/- 10.6%). Although prior regimens of busulfan (BU) or interferon (IFN) were equal risk factors for decreased %VC after BMT, decreases in DV/VA were more significant in CML patients who received IFN. CML patients, especially those who have received BU or IFN, should be carefully monitored for pulmonary function to prevent respiratory failure after BMT.

Acute Disease↗

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↗

[Details and indications of pallidotomy and thalamotomy for Parkinson's disease].

Pallidotomy has recently regained acceptance as an effective treatment for Parkinson's disease. From our 50 cases of unilateral pallidotomy and 10 cases of staged bilateral pallidotomy, details and indications of the procedure is described. The unilateral pallidotomy is quite effective for L-dopa induced dyskinesia, which usually completely disappears soon after the operation. The effect is long-lasting. When on-off phenomenon exists, unilateral pallidotomy improves off-stage rigidity or akinesia. Symptoms during on-stage are not changed. Indications of pallidotomy is that(1) L-dopa induced dyskinesia, and(2) on-off phenomenon. Bilateral pallidotomy, even by staged one, causes severe drooling, or speech disturbance(the volume of the voice decreases and the articulation worsens), and is not recommended. Vim thalamotomy is, on the other hand, the established treatment for tremor of Parkinson's disease or of essential tremor. The effect is long-lasting. Rigidity or akinesia is not expected to be improved so much.

Dyskinesia, Drug-Induced↗