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Biomedical subjects

K Mishima

Publications and source records attributed to K Mishima.

At least 145 records · Page 8Linked to original sources

The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP(+)-lesioned mice.

Orally administered Madopar (levodopa/benserazide 4:1) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP(+)-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.

1-Methyl-4-phenylpyridinium↗

Epstein-Barr virus in patients with polymorphic reticulosis (lethal midline granuloma) from China and Japan.

BACKGROUND: Polymorphic reticulosis is one of several diseases constituting lethal midline granuloma (LMG). Previous immunohistochemical studies suggested a T-cell nature of proliferating cells; the term nasal T-cell lymphoma (NTL-LMG) has since been used widely. The authors' previous study in Asian countries showed the clustering of Mongolian patients with NTL-LMG, but the frequency varied with geographic area; it was much higher in Korea and southwest Japan (Okinawa) than in Shanghai and Honshu, Japan. Recently an etiologic role of Epstein-Barr virus (EBV) for the development of NTL-LMG has been postulated. METHODS: In this study, the presence of EBV and human T-cell lymphocytic leukemia virus type 1 (HTLV-1) genomes were examined in NTL-LMG patients from Southwest Japan (Okinawa, 10 patients), another Japanese district (Honshu, 21 patients), and Shanghai, China (5 patients). All of the tissues from different geographic sites were analyzed at one central location. RESULTS: Immunohistochemistry showed that proliferating large cells were positive for CD43 and/or CD45RO, identical with reported NTL-LMG cases. Polymerase chain reaction (PCR) revealed the presence of EBV genome in the NTL-LMG lesions, but the frequency varied according to the geographic area: 67% in Okinawa, 33% in Honshu, and 100% in Shanghai. In situ hybridization provided positive signals in the nuclei of proliferating cells. Expression of latent membrane protein in the proliferating cells of cases positive for EBV by PCR and in situ hybridization was confirmed. CONCLUSIONS: The results suggest that the EBV may play a role in the development of NTL-LMG. However, the variation of frequency of EBV genome in different geographic locations suggests that EBV infection may not be an indispensable condition for the disease.

Adolescent↗

Opposite effects of the overexpression of protein kinase C gamma and delta on the growth properties of human glioma cell line U251 MG.

In order to address the question of whether protein kinase C (PKC) is involved in the growth regulation of human glioma cells, we introduced PKC cDNA expression vectors into a human glioma cell line, U-251 MG, and established sets of stable cell clones that overexpress PKC gamma or delta. Cell clones obtained by the transfection of PKC gamma cDNA express 3.6 to 5 times more PKC activity than parental cells that express predominantly endogenous PKC alpha. These PKC gamma overexpressing cell clones show an increased rate of growth in monolayer culture, increased colony-forming efficiency on soft agarose, and increased DNA synthesis in response to epidermal growth factor and basic fibroblast growth factor. Cell clones obtained by transfection with PKC delta cDNA express 2 to 10 times more PKC than that produced endogenously. PKC delta overexpressing cells show a decreased rate of growth and decreased colony-forming efficiency. However, these PKC delta cell clones show no significant changes in responsiveness to the growth factors described above. These results clearly indicate that different PKC family members have distinct regulatory functions in cell growth and that PKC is involved in several aspects of the growth regulation of human glioma cells.

Cell Division↗

Frequency dependence of electric-field-induced orientation of myelin tubes.

Orientation induced by an alternating electric field was studied for myelin tubes of egg phosphatidylcholine (egg-PC) in water and in KCl electrolyte solution. The orientation was also studied for myelin tubes of egg-PC/cholesterol mixtures in water. The orientation effect was measured by the bending curvature of myelin tubes with hairpin-like deformation at frequencies between 10 kHz and 20 MHz. The bending deformation of egg-PC myelin tubes in water decreased abruptly with a decreasing frequency within the low-frequency range below 100 kHz, and shrinkage of myelin tubes was often observed. The bending deformation decreased as the frequency was increased in a higher frequency range. The profile of the frequency dependence for egg-PC in KCl solution was similar to that in water but shifted towards a higher frequency. At low KCl concentrations below 3 mM, the relaxation frequency increased proportionally with increasing an KCl concentration, which was due to a proportional increase in the conductivity of the surrounding medium. Similar profiles of the frequency dependence were observed for egg-PC/cholesterol mixtures but with no shift in the relaxation frequency. These data in the high-frequency range fitted well with calculations based on theoretical equations for the electric-field-induced orientation of nonspherical particles. The conductivity of myelin tubes was estimated to be in the order of 10(-4) S/m in water and of 10(-3) S/m at the low KCl concentrations. The bending modulus of a bilayer membrane was estimated to be (1.0 +/- 0.5) x 10(-19) J for egg-PC in water. No change in the bending modulus was observed for egg-PC in KCl solution. However, for egg-PC/cholesterol mixtures in water, the bending modulus abruptly increased to (1.8 +/- 0.5) x 10(-19) J at a cholesterol concentration of 40 mol%.

Egg Yolk↗

Amelioration by aniracetam of abnormalities as revealed in choice reaction performance and shuttle behavior.

To delineate the possible effects of aniracetam PO on abnormal behaviors, we analyzed disrupted shuttle behavior and choice reaction (CR) performance in both aged and juvenile animals subjected to an ischemic (permanent occlusion of both carotid arteries)-hypoxic (17-min exposure to 93% N2 and 7% O2 mixture gas) or ischemic (20-min occlusion of both carotid arteries) insult and/or treated with methamphetamine given IP. Aniracetam at single PO doses of 10 and 30 mg/kg significantly decreased the number of incorrect lever pressings induced by IP methamphetamine in young adult rats subjected to the CR test battery. A 21-day PO regimen with aniracetam (30 mg/kg/day) resulted in an increase in the number of correct responses and a decrease in the CR latency as detected in the CR task with young adult rats inflicted with an ischemic-hypoxic insult. Aniracetam (1-100 mg/kg PO) was also evaluated in the electrostimulation-induced hyperreactivity assay (an increase in the number of shuttle responses) in both juvenile and aged mice subjected to a 20-min ischemic insult; there again a significant improvement of performance was clearly observed. The outcomes of these behavioral pharmacological analyses suggest that aniracetam has the ability to normalize the disrupted behavior, cognition, and self-regulation or decision-making process in a comprehensive way.

Animals↗

Estimation of mitral valve area in patients with mitral stenosis by the flow convergence region method: selection of aliasing velocity.

OBJECTIVES: We attempted to determine the most suitable aliasing velocity for applying the hemispheric flow convergence equation to calculate the mitral valve area in mitral stenosis using a continuity equation. BACKGROUND: The flow convergence region method has been used for calculating mitral valve area in patients with mitral stenosis. However, the effect of varying aliasing velocity on the accuracy of this method has not been investigated fully. METHODS: We studied 42 patients with mitral stenosis using imaging and Doppler echocardiography. Aliasing velocities of 17, 21, 28, 34, 40 and 45 cm/s were used. The transmitral maximal flow rate (Q [ml/s]) was calculated using the hemispheric flow convergence equation Q = 2 x pi x R2 x AV x alpha/180, where R (cm) is the maximal radius of the flow convergence region, AV is the aliasing velocity, and alpha/180 is a factor accounting for the inflow angle (alpha). Mitral valve area (A [cm2]) was calculated according to the continuity equation A = Q/V, where V (cm/s) is the peak transmitral velocity by the continuous wave Doppler method. RESULTS: Mitral valve area was progressively underestimated with increasing aliasing velocity. The actual and percent differences noted between the mitral valve area by the flow convergence region method and that by two-dimensional echocardiographic planimetry were -0.06 +/- 0.23 cm2 (mean +/- SD) and 0.09 +/- 15.7% at an aliasing velocity of 21 cm/s, increasing gradually with increasing aliasing velocity, and were -1.24 +/- 0.9 cm2 and -72.56 +/- 16.4% at an aliasing velocity of 45 cm/s. Mitral valve areas estimated by the flow convergence region method at an aliasing velocity of 21 cm/s in 11 patients with associated > 2+ mitral regurgitation (2.12 +/- 1.17 cm2) and 8 with associated > 2+ aortic regurgitation (1.28 +/- 0.71 cm2) were not significantly different using planimetry (2.24 +/- 1.39 cm2, p > 0.05 and 1.27 +/- 0.74 cm2, p > 0.05, respectively) but were significantly different by the pressure half-time method (1.59 +/- 1.12 cm2, p < 0.001 and 1.63 +/- 0.93 cm2, p < 0.01, respectively). CONCLUSIONS: This study indicated the most appropriate aliasing velocity for the accurate estimation of mitral valve area in patients with mitral stenosis.

Adolescent↗

Lesch-Nyhan syndrome: successful prevention of lower lip ulceration caused by self-mutilation by use of mouth guard.

Lesch-Nyhan syndrome (LNS) is a disorder caused by congenital absence of a purine metabolic enzyme, hypoxanthine guanine phosphoribosyl-transferase (HGPRT). This syndrome is characterized clinically by hyperuricemia and neurologic features including choreoathetoid spasticity, self-mutilation, and mental retardation. We report on a patient in whom self-mutilation of the lower lip was suppressed with the help of a mouth guard made from soft resin.

Humans↗

Lethal midline granuloma in Okinawa with special emphasis on polymorphic reticulosis.

Lethal midline granuloma (LMG) is a clinical term used to describe a condition which may be manifested histologically as Wegener's granulomatosis (WG), polymorphic reticulosis (PR), and malignant lymphoma (ML). WG is an inflammatory disease, and PR and ML are considered to represent a neoplastic proliferation of lymphoreticular cells. In this report, twenty-two cases of LMG in Okinawa were examined. The frequency of LMG per 100,000 outpatients of the ear, nose and throat clinic in Okinawa was 67, and the higher frequency of PR (27) and ML (34) in Okinawa than in other districts of Japan was characteristic. Polymerase chain reaction, in situ hybridization, and immunohistochemical studies showed that the proliferating cells in PR were CD43+ and simultaneously contained Epstein-Barr viral genome in their nuclei. The higher frequency of PR and ML in Okinawa is discussed in conjunction with a review of pertinent literature: multiple factors including genetic, viral environmental, and socioeconomic factors seem to affect the frequencies of these diseases.

Adult↗

Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia.

Fourteen inpatients with dementia showing sleep and behavior disorders (average age = 75 years), and 10 control elderly people (average age = 75 years) were carefully observed for 2 months. Four weeks of morning light therapy markedly improved sleep and behavior disorders in the dementia group. The measurement of sleep time and the serum melatonin values suggests that sleep and behavior disorders in the dementia group are related to decreases in the amplitude of the sleep-wake rhythm and decreases in the levels of melatonin secretions. Morning light therapy significantly increased total and nocturnal sleep time and significantly decreased daytime sleep time. These results indicate that morning bright light is a powerful synchronizer that can normalize disturbed sleep and substantially reduce the frequency of behavior disorders in elderly people with dementia.

Aged↗

Carcinoma of stomach and breast with lymphoid stroma: localisation of Epstein-Barr virus.

AIMS: To determine the presence of Epstein-Barr virus (EBV) genome in six patients (three with gastric and three with breast carcinoma) with severe small lymphoid cell infiltration. METHODS: The polymerase chain reaction and in situ hybridisation were used to detect EBV genome. The number and distribution of T and B lymphocytes were evaluated by immunohistochemistry. RESULTS: Histologically all of the patients had poorly differentiated tumours. Immunohistochemistry showed that T cells predominated in three cases, B cell in two, and almost equal numbers in one case. PCR showed that the EBV genome was present in two cases each of gastric and breast carcinoma. In situ hybridisation for EBV genome provided positive signals only in the small lymphoid cells in one gastric and two breast carcinomas giving a positive reaction for EBV genome by PCR. The gastric and breast cancer cells did not give positive signals. CONCLUSIONS: Severe lymphoid cell infiltration in gastric and breast carcinoma does not necessarily indicate that these tumours are associated with EBV. Larger numbers of cases will need to be studied to confirm this.

Adult↗

3-O-methyldopa attenuates the effects of Madopar on the haloperidol-induced cataleptic behavior and the locomotor activity in the mouse.

The effects of Madopar (levodopa plus benserazide) on the cataleptic behavioral response to haloperidol and on the locomotor activity in mice were quantitatively compared before and after the administration of 3-O-methyldopa (3OMD). The intraperitoneal administration of 3OMD (200-400 mg/kg) alone did not modify the haloperidol (1.0 mg/kg s.c.)-induced catalepsy. Madopar, depending on the dose regimen, markedly antagonized the haloperidol-induced catalepsy. Pretreatment with 3OMD tended to reverse the antagonistic property of Madopar on the cataleptic behavior in response to haloperidol. The ability of 3OMD to significantly inhibit Madopar effects was observed in the locomotor testing paradigm; the locomotor hyperactivity in Madopar-treated animals was significantly inhibited by a prior intraperitoneal injection of 3OMD. The results from our animal experiments may provide further evidence that impediment of 3OMD formation is meaningful in the treatment of Parkinson's disease with Madopar or levodopa.

Animals↗

Modulation of tumor immunogenicity of rat glioma cells by s-Myc expression: eradication of rat gliomas in vivo.

The Myc family proteins represented by c-Myc are thought to play a crucial role in cellular proliferation, differentiation, transformation, and apoptosis. In this study, we demonstrated the novel role for a Myc family protein in elicitation of immunogenic phenotypes in tumor cells. Injection of rat 9L or C6 glioma cells, together with the s-myc gene linked to the cytomegalovirus promoter, completely prevented formation of both brain tumors and s.c. tumors derived from the parental glioma cells. However, introduction of the s-myc gene had no inhibitory effect on development of B104-derived neuroblastoma. In addition, unlike the s-myc gene, injection of the c-myc or wild type p53 (wt-p53) gene together with glioma cells did not modulate the tumor immunogenicity and resulted in formation of gliomas in the animals. These findings suggest that s-Myc expression may stimulate the presentation of a tumor antigen common to 9L and C6 cells to T lymphocytes and augment the activity of the host immune system, resulting in prevention of glioma formation in vivo. This success in tumor eradication indicates the possibility of application of the s-myc gene for gene therapy of human brain tumors.

Animals↗

Posterior chamber intraocular lens implantation in filtered or nonfiltered glaucoma eyes.

Cataract extraction and posterior chamber intraocular lens (PC-IOL) implantation was carried out in 45 glaucoma eyes that had undergone glaucoma filtering surgery (Group A), and in 47 glaucoma eyes in which intraocular pressure (IOP) was well controlled with medication (Group B). To analyze the effects of PC-IOL implantation on the control of IOP and the functioning of the filtering bleb, a life-table analysis using the Kaplan-Meier method was carried out. In Group A the probability that IOP control will not worsen at 2 years was 56 +/- 12 (SE)% in eyes where a functioning filtering bleb had existed preoperatively. The probability that the filtering bleb was not cicatrized at 2 years postoperatively was 44 +/- 11 (SE)%. In Group B the postoperative IOP on the first postoperative day was significantly higher than the preoperative level in primary open angle glaucoma (POAG) eyes, while no such difference was seen in primary angle closure glaucoma (PACG) eyes. The postoperative IOP was significantly lower than the preoperative level from 3 to 6 months postoperatively in POAG eyes and from 1 to 12 months postoperatively in PACG eyes. Medication did not differ significantly pre- and postoperatively. In 64 +/- 11 (SE)% of POAG and 63 +/- 15% of PACG eyes the IOP control did not worsen at 2 years. In 70% of the eyes the IOP control improved postoperatively, and was maintained for 2 years with the probability of 44 +/- 12 (SE)%.

Aged↗

The s-Myc protein having the ability to induce apoptosis is selectively expressed in rat embryo chondrocytes.

Gene transfection experiments demonstrated that over-expression of the s-myc gene under the control of a human metallothionein promoter induced apoptosis in cells such as rat and human glioma cells. In contrast to c-Myc-mediated apoptosis requiring withdrawal of serum growth factors, s-myc expression induced apoptosis in glioma cells in the presence of 10% fetal calf serum. Whereas, s-Myc-mediated apoptosis was suppressed in proportion to the increase of bcl-2 expression as seen in c-Myc mediated apoptosis. The s-myc gene was expressed in rat embryo cells being committed to differentiate to hypertrophic chondrocytes which undergo programmed cell death. CAT assay demonstrated that in the NH2-terminal region, the s-Myc protein contains a domain structure required for expression of transactivation activity that is approximately six times higher than that of c-Myc. Therefore, these findings strongly suggest that s-Myc may play an important role in transcription regulation of a set of genes whose expression induces programmed cell death in vitro and in vivo.

3T3 Cells↗

NMR studies of G:A mismatches in oligodeoxyribonucleotide duplexes modelled after ribozymes.

The structures of two oligodeoxyribonucleotide duplexes, the base sequences of which were modelled after both a hammerhead ribozyme and a small metalloribozyme, were studied by NMR. Both duplexes contain adjacent G:A mismatches; one has a PyGAPu:PyGAPu sequence and the other a PyGAPy:PuGAPu sequence. It is concluded on the basis of many characteristic NOEs that in both duplexes G:A base pairs are formed in the unique 'sheared' form, where an amino proton instead of an imino proton of G is involved in the hydrogen bonding, and G and A bases are arranged 'side by side' instead of 'head to head'. A photo-CIDNP experiment, which gives unique and independent information on the solvent accessibility of nucleotide bases, also supports G:A base pairing rather than a bulged-out structure of G and A residues. This is the first demonstration that not only the PyGAPu:PyGAPu sequence but also the PyGAPy:PuGAPu sequence can form the unique sheared G:A base pairs. Taking the previous studies on G:A mismatches into account, the idea is suggested that a PyGA:GAPu sequence is a minimum and essential element for the formation of the sheared G:A base pairs. The sheared G:A base pairs in the PyGAPu:PyGAPu sequence are suggested to be more stable than those in the PyGAPy:PuGAPu sequence. This is explained rationally by the idea proposed above.

Base Sequence↗

Malignant lymphoma of the uterus. Report of seven cases with immunohistochemical study.

BACKGROUND: Uterine lymphoma is a rare disease; therefore, information regarding histologic type, immunophenotype of tumor cells, and etiologic factors are limited. METHODS: Seven patients with uterine lymphoma, three from the corpus and four from the cervix, were collected by a nationwide study in Japan. Selection of cases was preferentially made from the "Annual of Pathologic Autopsy Cases in Japan." RESULTS: All cases with cervical lymphoma presented with vaginal bleeding. Abdominal pain or backache was observed in patients with corpus lymphoma. The age ranges of patients with corpus and cervical lymphomas were 46-78 years of age (mean, 63 years) and 30-71 years of age (mean, 53 years), respectively. Information about clinical staging was available for six patients; two patients with Stage I, three patients with Stage II, and one patient with Stage III. A definite diagnosis of uterine lymphoma was made by biopsy in all cases. Total hysterectomy, with or without bilateral salpingo-oophorectomy, was carried out in three patients, and tumor resection was carried out in one patient. Adjuvant therapy was given in six cases. Follow-up showed that five patients died due to tumor within 1 year of treatment. Histologically, all cases were non-Hodgkin lymphoma showing a diffuse pattern of proliferation. All but one were diffuse large cell type. Immunohistochemistry revealed the tumor cells in all cases were of B-cell nature. Expression of HLA-DR antigen was evaluable in four cases, of these three showed an increased expression on the vascular endothelium. CONCLUSIONS: Uterine lymphoma comprises exclusively B-cell type.

Adult↗