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Biomedical subjects

K Oka

Publications and source records attributed to K Oka.

At least 19 recordsLinked to original sources
PubMed2006

Spindle cell carcinoma arising in the pharynx, with granulocytosis and high serum granulocyte colony stimulating factor titre.

We report the case of a 67-year-old man with a left pharyngeal tumour, whose peripheral blood showed granulocytosis (white blood cell count, 58,300/microl) and a high serum granulocyte colony stimulating factor titre (184 pg/ml). The tumour showed pleomorphic proliferation of atypical spindle cells in a myxomatous stroma, revealing a sarcomatous pattern. The spindle-shaped neoplastic cells had irregularly shaped nuclei, a thick nuclear membrane, prominent eosinophilic nucleoli and abundant cytoplasm. They strongly expressed wide-spectrum keratin, cytokeratins (CAM5.2, MNF116), vimentin and vascular endothelial growth factor. A few neoplastic cells expressed granulocyte colony stimulating factor. A spindle cell carcinoma was diagnosed. This may be the first documented case of a granulocyte colony stimulating factor producing cancer arising in the pharynx. The patient died four months after the initial symptoms appeared.

Aged↗
PubMed2006

Sustained phenotypic correction in a mouse model of hypoalphalipoproteinemia with a helper-dependent adenovirus vector.

We examined the efficacy and host response to the adenovirus (Ad)-mediated delivery of human apolipoprotein A-I (APOA1) gene to the liver of APOA1(-/-) mice. Administration of a first-generation vector (FGAd-AI) resulted in a transient appearance of APOA1 in plasma and induced an anti-APOA1 antibody titer, whereas treatment with a helper-dependent vector (HDAd-AI) resulted in sustained APOA1 expression without inducing an antibody titer. With these results, we studied the effects of FGAd vectors on APOAI expression by HDAd-AI vector. Co-treatment with an FGAd vector inhibited HDAd-AI- mediated APOA1 expression independent of transgene cassettes, but only FGAd-AI induced a humoral response. Furthermore, APOA1 mRNA levels in mice co-treated with FGAd vectors were much lower than those expected from the vector copy number, suggesting that DNA of FGAd vectors interferes with the HDAd-AI vector's APOA1 promoter. A single treatment with an HDAd-AI vector produced a supraphysiological plasma APOA1 level that gradually declined to about half the normal human level over the course of 2 years, associated with a plasma cholesterol level that is persistently higher than that in controls. This investigation provides the proof of principle that liver-directed HDAd gene delivery is effective for the long-term phenotypic correction of monogenic hypoalphalipoproteinemia.

Adenoviridae↗
PubMed2006

Laser based angle-resolved photoemission, the sudden approximation, and quasiparticle-like spectral peaks in Bi2Sr2CaCu2O(8+delta).

A new low photon energy regime of angle-resolved photoemission spectroscopy is accessed with lasers and used to study the high T(C) superconductor Bi2Sr2CaCu2O(8+delta). The low energy increases bulk sensitivity, reduces background, and improves resolution. With this we observe spectral peaks which are sharp on the scale of their binding energy--the clearest evidence yet for quasiparticles in the normal state. Crucial aspects of the data such as the dispersion, superconducting gaps, and the bosonic coupling kink are found to be robust to a possible breakdown of the sudden approximation.

Journal Article↗
PubMed2006

[The psychopathology of depersonalization].

In his classic overview, Mayer-Gross indicated two clinical features of depersonalization to be taken as starting points for future investigation: excessive difficulty in describing it and its relatively rare appearance in organic disorders. Neither characteristic has so far been discussed sufficiently in psychopathology and neurobiology. In this article, we examine the language aspect of depersonalization by comparisons with aphasia, in which the two objects of study described by Mayer-Gross, speech and organic disorders, intertwine. Concerning amnestic aphasia, Gelb and Goldstein insist that an object cannot be grasped as a generally understood fact using a categorical attitude but only experienced subjectively in its this-ness with a concrete attitude. The particular experience of depersonalization is the reverse of that in amnestic aphasia, as the relation of the depersonalized patient to this-ness is disturbed but an ideal view of the generality remains.

Anomia↗
PubMed2006

Unusual remnant thymic tissue in an adult mimicking malignant neoplasm: escape from age-related involution.

Here we report on a 55-year-old man with an abnormal anterior mediastinal shadow and multiple nodules in the thymus, which increased in size over a period of 15 months. He was diagnosed with early prostatic cancer, and treated with chemotherapy. Although no definite preoperative diagnosis was obtained, surgery was performed because of the possibility of malignant neoplasm or metastasis. Extended thymectomy was performed and pathological examination revealed that the nodules were remnant thymic tissue and not malignant lesions. Although the cause of this unusual remnant thymic tissue remains unclear, it may have been related to autoimmune or endocrinological disease.

Diagnosis, Differential↗
PubMed2005

Optimal dose and target trough level in cyclosporine and tacrolimus conversion in renal transplantation as evaluated by lymphocyte drug sensitivity and pharmacokinetic parameters.

We evaluated the relative clinical potency of cyclosporine (CyA) and tacrolimus (Tac) using pharmacodynamic and pharmacokinetic parameters of the drug to obtain the most suitable converting dose and target trough level. The relative pharmacodynamic potency was examined by the mean ratio of drug concentrations giving 50% inhibition of blastogenesis of lymphocytes (IC50) in 66 chronic renal failure patients. The relative potency estimated from clinical pharmacokinetic parameters was examined by the mean ratio of each pharmacokinetic parameter value of CyA versus Tac. The pharmacokinetic parameters were estimated by 12-hour monitoring of drug blood concentrations in seven CyA patients and seven Tac patients. The mean IC50 ratio of CyA and Tac (CyA/Tac of IC50) was 25.1. The mean area under the concentration-time curve (AUC) ratio (CyA/Tac of AUC) was 25.5, the mean trough level (C(min)) ratio (CyA/Tac of C(min)) was 13.2, and the mean dose per body weight ratio was 25.2. The relative potency estimated from AUC that is the most reliable pharmacokinetic parameter for the estimation of clinical efficacy of calcineurin inhibitors appeared to agree with the relative pharmacodynamic potency estimated from IC50. The data suggest that TAC 25-fold more potent than CyA, which represents a suitable converting dose ratio, and that target trough level of CyA is about 13-fold greater than Tac based on CyA/Tac of C(min). We conclude that these relative values may be useful to estimate the suitable dose and target trough levels to convert between CyA and Tac.

Area Under Curve↗
PubMed2005

Evaluation of appropriate blood level in continuous intravenous infusion from trough concentrations after oral administration based on area under trough level in tacrolimus and cyclosporine therapy.

The target blood concentrations of tacrolimus (TAC) and cyclosporine (CYA) during continuous intravenous infusion (C(ss)) have been determined based on clinical experience. However, it is desirable that C(ss) should be set so that the AUC after intravenous infusion is equal to the AUC after oral administration (AUC(po)). Accordingly, we performed 12-hour monitoring of blood concentrations to calculate C(ss) from the blood trough levels (C(TL)) on 15 kidney recipients administered TAC and 12 recipients administered CYA (Neoral). We used an area under the trough level (AUTL) as a new pharmacokinetic parameter. The C(ss) was evaluated from C(TL), AUC(po), and AUTL was calculated to be C(ss) = C(TL) x (AUC(po)/AUTL). In addition, AUTL/AUC(po) ratio and blood peak/trough level ratio (C(max)/C(min)) were examined to compare pharmacokinetics of TAC and CYA. The formula for TAC was C(ss) = C(TL) x 1.40 and that for CYA, C(ss) = C(TL) x 2.55. The calculated target C(ss) of TAC was 1.40 times that of C(TL), which was similar to the present clinical C(TL). In contrast, the calculated target C(ss) of CYA was 2.55 times the C(TL), and therefore an extremely high C(ss) was necessary to obtain a sufficient AUC that will be available after oral administration. Consequently, intravenous administration of CYA twice a day was considered to be more appropriate to obtain sufficient CYA pharmacokinetics, rather than a continuous intravenous administration. We conclude that the formula, C(ss) = C(TL) x (AUC(po)/AUTL) was useful to calculate the target blood concentration of calcineurin inhibitors when changing from continuous intravenous infusion to oral administration of these drugs.

Administration, Oral↗
PubMed2005

Pharmacokinetic differences between morning and evening administration of cyclosporine and tacrolimus therapy.

We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were administered equally divided doses of drugs twice daily orally. Blood samples were taken before and 1, 2, 3, 4, 6, and 12 hours after NEO or TAC administration in the morning and evening. The pharmacokinetic parameters were compared between morning and evening administrations of both drugs. AUC0-12, AUC0-4, C(max), C2, and C(max)/C(min) of NEO and TAC were significantly lower during the evening compared with morning administrations. C(min) values were significantly higher in the evening. T(max) of NEO was longer in evening, although there was not a significant difference; T(max) of TAC was significantly longer in the evening. We found that NEO and TAC administrations in the evening resulted in reduced bioavailability and delayed absorption when compared with drug administrations in the morning. It was thought that the difference in bioavailability between morning and evening administrations was smaller with TAC, because TAC shows lower peak levels and a flatter blood concentration curve than NEO. C(min) was higher after evening administration than morning because of delayed absorption, though the bioavailability of both drugs decreased in the evening. These results suggest that we have to appreciate apparently high trough levels.

Administration, Oral↗
PubMed2005

Increased expression of renin in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal transplant failure in the first decade posttransplant. The precise pathogenetic mechanism for CAN is not completely understood. A possible role of renin-angiotensin system for CAN has been suggested through clinical observations that angiotensin-converting enzyme inhibition and angiotensin II receptor blockers prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy specimens was examined immunohistochemically in 23 renal transplant recipients diagnosed with CAN Biopsy specimens obtained from seven recipients with stable renal function were examined as controls. Histologic evaluation was performed based on the Banff 97 classification. RESULTS: Renin-positive cells were found in the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both groups. When the number of renin-positive cells in JGA was defined as a renin index, it was significantly higher in the CAN than the control group (P = .007). There was no significant difference in age, interval between transplantation and biopsy, and blood pressure between groups. Only a significantly higher serum creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive cells in JGA suggest a significant role of the intrarenal renin-angiotensin system activation in the development of CAN.

Adult↗
PubMed2004

[A contribution to the psychopathology of obsessive-compulsive disorder].

On the basis of recent developments in neuroscience, modern neuropsychology makes great contributions to the psychopathology of obsessive-compulsive disorder (OCD). Those studies pay little attention to the will because of their cognitive orientation. However, the will forms an essential aspect of OCD according to Jaspers and Schneider. Based on a clinical case we discuss OCD from the point of view of will psychology. As our case concerns a schizophrenic psychosis, we focus here on OCD appearing in schizophrenia. For this approach we refer to classic neuropsychology which deals intensively with problems of the will. Accordingly, patients suffering from brain injuries are confined to habitual activities which follow unintentionally from the present situation. This sort of present-related spontaneousness is expressed in the concept "becoming." On the other hand, patients suffering from OCD are alienated from habitual activities. Lastly we discuss the relation between schizophrenia and OCD.

Activities of Daily Living↗
PubMed2004

Risk factors for graft loss in patients with recurrent IGA nephropathy after renal transplantation.

BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys has been reported to be >50%. Although recurrent IgAN has a benign clinical course, recent data suggest that it leads to graft loss in a substantial number of patients. METHODS: We performed a retrospective single-center analysis of 34 renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients, of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN. Recurrent transplant IgAN was more often detected in men and at later timepoints after post-transplantation. Four patients with recurrent transplant IgAN progressed to graft failure. Progression to graft failure was associated with worsened renal function, higher systolic blood pressure, and the lack of presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA typing, and immunosuppression did not show a relation to recurrence or graft loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft survival and risk factors for graft loss due to recurrent IgAN were similar to those among IgAN in native kidneys.

Adult↗
PubMed2004

Low-density lipoprotein receptor gene therapy using helper-dependent adenovirus produces long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia.

We tested the efficacy of low-density lipoprotein receptor (LDLR) therapy using helper-dependent adenovirus (HD-Ad), comparing it with that of very low-density lipoprotein receptor (VLDLR), an LDLR homolog. We treated high cholesterol diet fed LDLR-/- mice with a single intravenous injection of HD-Ad expressing monkey LDLR (1.5 x 10(13) or 5 x 10(12) VP/kg) or VLDLR. Throughout the 24-week experiment, plasma cholesterol of LDLR-treated mice was lower than that of VLDLR-treated mice, which was in turn lower than that of PBS-treated mice. Anti-LDLR antibodies developed in 2/10 mice treated with high-dose HD-Ad-LDLR but in none (0/14) of the other treatment groups. HD-Ad-treated mice displayed significant retardation of atherosclerotic lesion progression. We next tested the long-term efficacy of low-dose HD-Ad-LDLR injected into 12-week-old LDLR-/- mice. After 60 weeks, atherosclerosis lesions covered approximately 50% of the surface of aortas of control mice, whereas aortas of treated mice were essentially lesion-free. The lipid lowering effect of HD-Ad-LDLR lasted at least 108 weeks (>2 years) when all control mice had died. In addition to retarding lesion progression, treatment caused lesion remodeling from a vulnerable-looking to a more stable-appearing phenotype. In conclusion, HD-Ad-mediated LDLR gene therapy is effective in conferring long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia.

Adenoviridae↗
PubMed2004

Comparison of histopathological characteristics of allograft biopsy between responder and non-responder to antiproteinuric effect of angiotensin-converting enzyme inhibitor (ACEI).

Angiotensin-converting enzyme inhibitor (ACEI) has become recognized as agents that have renoprotective effects in the treatment of progressive renal diseases including post-transplant kidneys. Previously we demonstrated the safety and effectiveness of ACEI treatment on the hypertensive proteinuric post-transplant patients (N = 10) who had been followed up for 12 months. However, not all patients show good response in urinary protein reduction. We aimed to analyse the histopathological factor(s) affecting the responsiveness of proteinuria to ACEI treatment. Fourteen post-transplant patients with proteinuria who were treated with ACEI and underwent allograft biopsy were analysed. Eight patients showed 50% or more reduction in proteinuria (responder). The other 6 patients showed less (< 50%) reduction in proteinuria (non-responder). There was no difference in clinical characteristics (BP, renal function, donor age, recipient body mass index), dietary sodium or protein intake, and diuretic use between the two groups. As a histopathological characteristic, glomerular size in responder group was significantly larger than that in non-responder group. This suggests that the large glomerular size at least partly contributes to the responsiveness in urinary protein reduction to ACEI treatment in kidney allograft recipients with proteinuria.

Adult↗
PubMed2003

Structure of end states for a Haldane spin chain.

Inelastic neutron scattering was used to probe edge states in a quantum spin liquid. The experiment was performed on finite length antiferromagnetic spin-1 chains in Y2BaNi1-xMgxO5. At finite fields, there is a Zeeman resonance below the Haldane gap. The wave-vector dependence of its intensity provides direct evidence for staggered magnetization at chain ends, which decays exponentially towards the bulk [xi=8(1) at T=0.1 K]. Continuum contributions to the chain-end spectrum indicate interchain segment interactions. We also observe a finite size blueshift of the Haldane gap.

Journal Article↗
PubMed2003

[Meaning of "becoming" in the Japanese psychopathologic view as compared with the German-speaking view].

Until now, Japanese cultural concepts such as "ki" and "aida" were used to introduce new perspectives to psychopathology. Universal concepts can also serve this purpose when the culturally different connotations are worked out. In this study,we discuss the concept "becoming," which is not only universal but also undoubtedly one of the key words in psychiatry. As is well known,Zutt made a contribution to psychopathology with a clear differentiation between "becoming" and "doing." It is interesting that some Japanese linguists also mentioned the same difference, namely that between the Japanese logic of "becoming" and the Western logic of "doing." Accordingly, tai-jin-kyôfu as anxiety about "becoming" is contrasted with sociophobia as anxiety about "doing." However, "becoming" in the sense of Zutt is different from the Japanese in three aspects,namely the physical, social and temporal ones. These differences refer to the various meanings of "nature." Finally,we mention the possibility of applying the Japanese term "becoming" to psychopathology.

Altruism↗
PubMed2003

Identification of two types of synaptic activity in the earthworm nervous system during locomotion.

In the ventral nervous system of the earthworm, a central pattern generator and motor neurons are activated during locomotion. We have previously reported that bath application of octopamine (OA) induces fictive locomotion in the earthworm, and the burst frequency of electrical activity from the first lateral nerves increases with OA concentration. However, there are no reports concerning locomotor neural networks in the earthworm. To identify neural networks involved in fictive locomotion, we optically monitored activity-dependent fluorescent staining in the earthworm ventral nerve cord (VNC) with a styryl dye, N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide (FM1-43), and a confocal laser scanning microscope. OA induces FM1-43 fluorescence in a dose-dependent manner, with bright fluorescent spots of 3-10 microm in diameter observed to be localized around specified neurons in the segmental ganglion of the VNC. We compared OA dose-response curves for FM1-43 fluorescence with the bursting frequency for fictive locomotion, and found that two types of curves could be identified: one fluorescence response shows a similar dose-dependency to that of the burst frequency, while another response has a higher sensitivity to OA. From these results, we suggest that OA acts as one of the neuromodulators for the earthworm locomotion. This is the first attempt to record motor and inter-neuronal activities simultaneously in a locomotor network in the earthworm.

Action Potentials↗
PubMed2003

Food texture differences affect energy metabolism in rats.

Dietary factors such as taste and nutrients are known to affect satiety and energy balance. We hypothesized that food texture might contribute to the regulation of energy metabolism through the process of mastication in the oral cavity as well. The effects of long-term feeding of different-textured pellets on body weight gain, adiposity, and thermogenesis were assessed. From weaning at 4 wks, rats were divided into 2 groups fed on either standard (controls) or soft pellets (soft-fed) that required less chewing with the same nutritional composition. At 26 wks, the soft-fed rats showed greater adiposity than did the controls. Daily food intake did not differ between the 2 groups. The increase in body temperature following feeding was significantly lower in the soft-fed rats. These results suggested that food texture affected energy metabolism by changing post-prandial thermogenesis. The long-term deficiency of thermogenesis associated with soft foods resulted in a greater tendency toward obesity.

Adipose Tissue↗