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Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 919 records · Page 51Linked to original sources

Human VEPs to isoluminant chromatic and achromatic sinusoidal gratings: separation of parvocellular components.

To extract the responses specific to the parvocellular system (color vision and form perception) in humans, visual evoked potentials (VEPs) in response to the onset of isoluminant chromatic (red-green) and achromatic (black-white) sinusoidal gratings were recorded in 15 young adults. Chromatic stimulation evoked a characteristic negative wave (N1) with peak latencies around 120 msec. The amplitude resembled an inverse U-shaped function against the spatial frequency with a peak at 2 c/deg. In contrast, VEPs to achromatic gratings showed different spatial frequency characteristics with a peak at 5.3 c/deg. With variations in the luminous intensity ratio between the red and green gratings, N1 was seen to respond maximally to isoluminant stimulation. These results indicate that the combined use of isoluminant chromatic and achromatic patterns could stimulate the parvocellular system selectively in humans.

Adult↗

Inflammatory cytokine production induced by an analogue of muramyl dipeptide MDP-Lys(L18) in rat macrophage cultures and dog synovial fluid.

To examine the involvement of cytokines in the mechanisms of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18)-induced arthritis, we analyzed interleukin-1 (IL-1), tumor necrosis factor (TNF), colony-stimulating factor (CSF), and neutrophil chemotactic factor (NCF) by bioassays in the rat macrophage-conditioned medium (Mluminal diameter-CM) stimulated by MDP-Lys(L18) in vitro and the synovial fluid from dogs treated subcutaneously with MDP-Lys(L18) for 14 days in vivo. The dog showed arthritis characterized by swelling of the knee joint, increased synovial fluid and thickened synovial membrane, and a single subcutaneous injection of MDP-Lys(L18) was previously shown to induced synovitis in rat tarsal joint. IL-1, TNF, CSF, and NCF activities in Mluminal diameter-CM were increased by MDP-Lys(L18), while only NCF activity was detected in the dog synovial fluid. Partial purification procedures revealed that NCF in Mluminal diameter-CM was not leukotriene B4 but a protein having heparin-affinity, and, in addition, immuno-reactive IL-8 was evident to be in Mluminal diameter-CM. The NCF activity in the dog synovial fluid was not inhibited by dialysis, showing that NCF is a protein substance, possibly a chemokine. These results suggest that MDP-Lys(L18) produces a chemokine, such as IL-8, which recruits neutrophils to the synovial membrane for subsequent development of synovitis in rats and dogs.

Acetylmuramyl-Alanyl-Isoglutamine↗

Differences in the reduced 18F-Dopa uptakes of the caudate and the putamen in Parkinson's disease: correlations with the three main symptoms.

It has been reported that the F-Dopa (FD) uptake in patients with idiopathic Parkinson's disease (PD) decreased significantly in the caudate and putamen when compared to controls. The FD uptake severely decreased in the putamen, while it was relatively spared in the caudate nucleus. We also previously reported that atypical parkinsonism with no or little tremor showed a homogeneously reduced FD uptake in both the caudate and the putamen. In this study we evaluated the caudate and the putaminal FD uptakes in relation to the three main symptoms in PD. The FD uptake was measured by PET with 6-L-[18F]fluorodopa in 17 patients with PD. The caudate and the putaminal FD uptake ratios to the cerebellum at 120 min were evaluated. The caudate and the putaminal FD uptake ratios in the patients with PD decreased as their clinical stages advanced. These decreases also correlated with the degree of rigidity and bradykinesia. However, such decreases did not correlate with the degree of tremor. The caudate-putamen index (CPI)(%), which was calculated by a formula based on the difference in the uptakes of the caudate and putamen divided by the caudate uptake, indicated 11.6 +/- 3.6, 16.5 +/- 5.5 and 18.3 +/- 4.1 in the group of no, mild and moderate tremor, respectively, and increased as the degree of tremor advanced. The CPI in the group of moderate tremor significantly increased from that in the group of no tremor (P < 0.04). However, the CPI did not correlate with the clinical stage, the degree of rigidity or the degree of bradykinesia. The FD/PET study therefore effectively demonstrated the severity of the clinical symptoms of rigidity and bradykinesia in patients with PD in correlation with a decrease in the FD uptakes in the caudate and the putamen, and it also demonstrated that the severity of tremor might have a different mechanism from that of such other symptoms as rigidity and bradykinesia.

Adult↗

Effects of bradykinin on the intracellular calcium concentration of pancreatic acinar AR42J cells.

We examined the effects of bradykinin (BK) on the intracellular free calcium concentration ([Ca2+]i) in rat pancreatic acinar AR42J cells. BK induced a dose-dependent rise in [Ca+2]i in AR42J cells between the concentrations of 10(-12)M and 10(-7)M. The BK-evoked response was not affected by the presence of Co2+ or the absence of extracellular calcium. This response was suppressed by neomycin or the B2 antagonist, but not by the B1 antagonist. The response was also attenuated by treatment with dexamethasone. These results suggest that BK increases [Ca2+]i through the B2 receptors by promoting the phosphatidyl inositol turn-over and that, in the process of azaserine-induced undifferentiation, the pancreatic acinar cells strongly express the BK receptors.

Animals↗

The effect of binocular stimulation on each component of transient and steady-state VEPs.

We recorded the monocular and binocular VEPs to the alternation of sinusoidal gratings in order to evaluate the binocular interaction in each component of transient and steady-state VEPs in 13 normal subjects. Three spatial frequencies (1.3, 2.6 and 5.3 c/deg) with a 90% contrast were used as visual stimuli. The latencies and amplitudes of N70 and P100 of the transient VEPs were measured. The steady-state VEPs were Fourier analyzed, and both the phase and amplitude of the second (2F) and fourth (4F) harmonic responses were obtained. Binocular interaction was influenced by spatial frequency such that a binocular summation or even an inhibition occurred. For the transient VEPs, a binocular summation was more pronounced in the amplitude of N70 than in that of P100 at all spatial frequencies. There were no significant effects of binocular stimulation on latencies of N70 or P100. However, the latencies of N70 and P100 showed different spatial frequency characteristics. For the steady-state VEPs, the amplitude of 2F revealed a binocular summation that was more pronounced at 5.3 c/deg, whereas the 4F amplitude showed binocular inhibition at 2.6 and 5.3 c/deg. The 2F phase showed binocular inhibition at all spatial frequencies, whereas no such inhibition was observed in the 4F phase. These results suggest that individual components of transient and steady-state VEPs are physiologically distinct and may therefore be generated from different neuronal populations in striate cortex.

Adult↗

Normal variability of the amplitude and phase of steady-state VEPs.

The present study quantifies the amplitude and phase variability of steady-state VEPs (S-VEPs) and compares this variability between subjects and between individual runs. The S-VEPs were recorded repeatedly in 14 normal subjects with varying spatial and temporal frequencies of sinusoidal gratings; 6 spatial frequencies (range 0.5-8.0 c/deg) with 3 temporal frequencies (4, 6 and 8 Hz) were used. A total of 75 responses were averaged and analyzed by the Fourier method. Four recordings were obtained in each spatio-temporal combination. In general, the phase data showed small inter- and intrasubject variability. As anticipated, the amplitude data showed a large degree of intersubject variability, although the intrasubject variability was very small. In addition, in some stimulus conditions the inter- and intrasubject variability increased, which thus suggested the existence of an optimal spatio-temporal combination. Therefore, these stimulus parameters should be taken into consideration when S-VEPs are applied in clinical practice.

Adult↗

Hypertrophy of the cerebral white matter in hemimegalencephaly.

We morphometrically measured the cut surface of the cerebral hemisphere and localized epidermal growth factor (EGF)-like immunoreactivity in 4 patients with hemimegalencephaly. On the affected side, the area of cerebral white matter was more than twice as large as that on the unaffected side, while the area of the cerebral cortex on the affected side was relatively small. EGF-like immunoreactivity was demonstrated in cortical neurons (4 of 4 patients) and glial cells (3 of 4 patients), notably in astrocytes. Significant enlargement of the cerebral white matter compared to the cerebral cortex and the expression of EGF-like molecules in astrocytes suggest excessive proliferation in the white matter with hemimegalencephaly and the possible relevance of EGF to these events.

Brain↗

Differential localization of TGF-beta-precursor isotypes in psoriatic human skin.

Transforming growth factor-beta (TGF-beta) can act as a multi-functional regulator of both cell growth and differentiation. Three isoforms of TGF-betas, namely TGF-beta 1 TGF-beta 2 and TGF-beta 3, have been identified in human tissues. Previously we reported the expression of TGF-beta isoforms in normal human skin. However little is known about the role of TGF-beta isoforms in the pathogenesis of psoriasis. Using the TGF-beta precursor-specific antibodies to strengthen the specificity, we studied the immunohistochemical distribution of TGF-betas 1-3 in psoriatic skin. TGF-beta 2, which was found in the intercellular space of all the layers of the epidermis in normal human skin, was decreased in the psoriatic epidermis. The intensity of immunoreactivity has the tendency to decrease in the lower epidermis rather than in the upper epidermis of the transitional lesion. In contrast, TGF-beta 3 was present in the subepidermal area of the psoriatic skin as in the normal human skin. TGF-beta 1 was observed in neither epidermis nor dermis in both normal and psoriatic skin. Since TGF-beta is a potent growth inhibitor for human keratinocytes, the decrease of TGF-beta 2 in the epidermis of psoriatic skin may contribute to epidermal hyperplasia, a hallmark of psoriasis.

Humans↗

Glucose metabolism in the cortical and subcortical brain structures in multiple system atrophy and Parkinson's disease: a positron emission tomographic study.

The brain glucose metabolism was studied by PET with 18F-FDG in 11 patients with multiple system atrophy (MSA) and 12 patients with idiopathic Parkinson's disease (PD). Seven of the 11 MSA patients were diagnosed as having olivopontocerebellar atrophy, two had striatonigral degeneration, while two demonstrated Shy-Drager syndrome. The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal, temporal and parietal cortical glucose metabolic rates and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolic rates in the MSA patients decreased significantly from the controls. The atrophy of the cerebellum and the brainstem in the MSA patients were scored by MRI. The cerebellar and brainstem glucose metabolism in the MSA patients decreased as the atrophy score in such regions advanced in each group; however, some patients with no atrophy showed a decreased glucose metabolism. Although the cerebellar and the brainstem glucose metabolism decreased in all MSA patients, such a decrease was not observed in the SND patients. The decrease in the glucose metabolism for the non-cortical regions in the MSA patients seems to be due to a diffuse depletion of the neurons not restricted to the nigrostriatal neurons. Deafferentation to the cerebral cortices seems to result in a decreased cortical metabolism. The differences in the glucose metabolism between MSA and PD as assessed by PET may be caused by the pathophysiological differences between MSA and PD, and such differences therefore appear to be useful when making a differential diagnosis between MSA and PD. The relative sparing of the brainstem and cerebellar glucose metabolism is considered to be a feature of patients with SND.

Adult↗

Repair of chronic tympanic membrane perforations with fibroblast growth factor.

A number of angiogenic growth factors have been shown to accelerate wound healing. Previous work has demonstrated that topical application of epidermal growth factor is effective in healing chronic tympanic membrane perforations in an animal model. Theoretically, fibroblast growth factor may result in a superior healed membrane through preferential stimulation of the fibroblasts within the middle layer of the tympanic membrane. To test this hypothesis, the effects of exogenously applied fibroblast growth factor on the chronically perforated tympanic membrane were evaluated. A buffered solution of fibroblast growth factor (25 microliters of fibroblast growth factor, 0.2 mg/ml) was administered to a Gelfoam pledget placed over chronic tympanic membrane perforations in chinchillas. Control ears were treated with Gelfoam and the buffer solution only. Complete closure of the tympanic membrane perforation was observed in 81% (13 of 16) of the fibroblast growth factor-treated ears, but in only 41% (7 of 17) of the controls (p = 0.05). Heading took place gradually, requiring an average of 4 weeks for the fibroblast growth factor-treated and 6.5 weeks for the control ears that healed. The relatively high healing rate for the control group does not imply that the pretreatment perforations were not chronic, rather there appears to be some efficacy to the control protocol of repeated applications of Gelfoam and buffer. A histologic analysis of the fibroblast growth factor-healed eardrums immediately after closure demonstrated hypertrophy of the squamous and fibrous layers of the tympanic membrane. Over time, the eardrum thinned to reach proportions similar to those of the normal tympanic membrane, including the presence of a substantial middle fibrous layer. A screening ototoxicity study revealed no structural damage to the organ of Corti after growth factor treatment. To assess the potential for systemic toxicity, blood and peripheral tissues were analyzed for radioactivity at time points during a 48-hour period after application of 25 microliters of 125I-fibroblast growth factor to the perforated tympanic membrane. More than 78% of the radioactivity remained at the application site. Given the tiny original dosage, the small fraction absorbed systemically is minuscule and highly unlikely to induce adverse effects in light of published toxicity data. On the basis of these promising safety and efficacy data in the chinchilla model, clinical trials of fibroblast growth factor in repair of chronic tympanic membrane perforations in human beings are being initiated.

Administration, Topical↗

A tyrosine kinase-like molecule is localized in the nuclear membrane of neurons: hippocampal behavior under stress.

Protein tyrosine kinases play important roles in the development of the mammalian nervous system during embryogenesis and in the maintenance of function of the adult brain. Using a semi-nested PCR technique based on a short amino acid motif of protein tyrosine kinases, we isolated a human genomic DNA encoding a peptide whose sequence was related to known mammalian protein tyrosine kinases. The expression was examined by Northern blot analysis, and transcripts were detected almost exclusively in the brain. The corresponding cDNA was sequenced, and it was revealed that the gene designated as byk coded for a receptor-like molecule with a motif of protein tyrosine kinase. Immunohistochemical analysis demonstrated that the Byk protein was expressed in neurons and was located in the nuclear envelope. To understand the physiological significance of the Byk protein, we investigated the behavior of this molecule in the hippocampus after ischemia. Byk-like immunoreactivity disappeared from the neurons in the fields CA1 through CA3 and the dentate gyrus of the hippocampus following 20 min of ischemia. After recirculation of blood flow, neurons in the CA3 field and the dentate gyrus re-expressed Byk-like antigen but CA1 neurons did not. Interestingly, Byk-like immunoreactivity was detected in microglial cells and astrocytes in the CA1 field that were activated after ischemia. Byk could be a new tool to study the neuron-glia and glia-glia interactions.

Amino Acid Sequence↗

Effects of electrical stimulation and morphine microinjection into periaqueductal gray on 5-hydroxyindole oxidation current in spinal cord of cats.

1. The effects of electrical stimulation and microinjection of morphine into the periaqueductal gray (PAG) on the 5-hydroxyindole oxidation current (280-300 mV) in laminae I-VI (800-2500 microns) of the spinal cord were examined using in vivo voltammetry in anesthetized cats. 2. Electrical stimulation of the PAG (PAG-S) both enhanced and attenuated the current. PAG-S increased the signal by 13.3 +/- 3.7% (laminae I-II: 800-1200 microns) or 19.0 +/- 3.6% (laminae V-VI: 1700-2500 microns) in comparison to control values. Attenuation by PAG-S decreased the signal by 15.3 +/- 2.6% (laminae I-II) or 13.3 +/- 2.0% (laminae V-VI) of control values. Naloxone antagonized signal enhancement by PAG-S. 3. Morphine (10 micrograms/microliter) microinjected into the PAG significantly increased the height of the signal (laminae I-II: 15.0 +/- 3.4%, laminae V-VI: 12.2 +/- 1.5%). Enhancement by microinjected morphine was antagonized by naloxone. In contrast, microinjected morphine also significantly decreased the signal by 10.4 +/- 2.7% (laminae I-II) and by 10.3 +/- 1.3% (laminae V-VI) of control values. 4. Microinjection of morphine and electrical stimulation of the PAG was observed both to enhance and attenuate the oxidation current of 5-hydroxyindole in the superficial and deeper dorsal horn. PAG may function to regulate the RVM-spinal serotonergic pathway, which modulates the transmission of nociceptive messages at the spinal cord.

Animals↗

Responses of plasma norepinephrine and renin-angiotensin-aldosterone system to dynamic exercise in patients with congestive heart failure.

BACKGROUND: Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in congestive heart failure (CHF). Responses of plasma norepinephrine in various degrees of heart failure have been investigated, but the responses of the renin-angiotensin-aldosterone system have not been studied in relation to the severity of CHF. The aim of this study was to determine if the responses of the renin-angiotensin-aldosterone system to exercise are augmented according to the severity of CHF. METHODS AND RESULTS: Ventilatory and neurohormonal responses were assessed in 38 patients with CHF (New York Heart Association class: I, 13 patients; II, 14 patients; III, 11 patients) and 11 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma norepinephrine, renin activity, angiotensin II, and aldosterone were measured at rest and at peak exercise. The increments in neurohormones were divided by peak oxygen consumption, and these ratios (norepinephrine exercise ratio, plasma renin activity-exercise ratio, angiotensin II-exercise ratio, aldosterone-exercise ratio) were compared among groups. Peak oxygen consumption and anaerobic threshold decreased progressively with the severity of CHF. Neurohormonal profiles at rest showed that plasma norepinephrine levels were significantly higher, and the renin-angiotensin-aldosterone system was augmented only in patients with class III CHF. Neurohormones increased during exercise both in patients with CHF and in normal subjects, but patients with class III CHF had significantly higher plasma renin activity (10.11 +/- 2.32 ng/mL/h), angiotensin II (73.9 +/- 14.2 pg/mL), and aldosterone (265.2 +/- 61.1 pg/mL) than did normal subjects. Plasma renin activity-exercise ratio, angiotensin II-exercise ratio, and aldosterone-exercise ratio in patients with class III CHF were significantly higher compared to normal subjects. This augmentation of the renin-angiotensin-aldosterone system was not observed in class I or II patients. Peak plasma norepinephrine levels were not different among normal subjects and subgroups of CHF patients, but the norepinephrine-exercise ratio was significantly higher in classes II and III CHF compared to normal subjects. CONCLUSIONS: These data suggest that neurohormonal excitation during exercise increases along with the severity of CHF when normalized for peak exercise level.

Aldosterone↗

Measurement of LET distribution and dose equivalent on board the space shuttle STS-65.

Space radiation dosimetry measurements have been made on board the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD)" utilizing silicon semi-conductor detectors and others are conventional detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. Using the RRMD detector, the first attempt of real-time monitoring of space radiation has been achieved successfully for a continuous period of 251.3 h, giving the temporal variations of LET distribution, particle count rates, and rates of absorbed dose and dose equivalent. The RRMD results indicate that a clear enhancement of the number of trapped particles is seen at the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent, while some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions for galactic cosmic ray particles (GCRs). Therefore, the main contribution to dose equivalent is seen to be due to GCRs in this low altitude mission (300 km). Also, the dose equivalent rates obtained by TLDs and CR-39 ranged from 146.9 to 165.2 microSv/day and the average quality factors from 1.45 to 1.57 depending on the locations and directions of detectors inside the Space-lab at this highly protected orbit for space radiation with a small inclination (28.5 degrees) and a low altitude (300 km). The LET distributions obtained by two different detectors, RRMD and CR-39, are in good agreement in the region of 15-200 keV/mm and difference of these distributions in the regions of LET < 15 keV/mm and LET > 200 keV/mm can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks.

Atlantic Ocean↗

Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumours.

The distribution of bone morphogenetic protein (BMP) type I receptors and the activin type I receptor (ActR-I) was investigated in 16 cases of human glioma and five cases of non-tumourous gliosis tissue by immunohistochemical technique. Both BMP type IA (BMPR-IA) and the type IB (BMPR-IB) receptors were detected in human glioma cells. A significant increase in BMPR-IB in tumour cells was observed in malignant glioma compared with both low-grade astrocytomas (n=16, P<0.005) and gliosis (n=13, P<0.001). However, enhancement of BMPR-IA staining was moderate and ActR-I staining was only weakly expressed in the malignant glioma tumours. Osteogenic protein (OP)-1/BMP-7, which is known to bind BMPR-IA, BMPR-IB and ActR-I, was expressed in nervous tissue and was also detected in anaplastic areas of malignant glioma. In contrast to the tissue materials, BMPR-IA was expressed to a stronger degree than BMPR-IB in human glioma cell lines; the growth of these cells was suppressed by OP-1. These results suggest the presence of BMP receptors and a functional role for BMPs in malignant glioma.

Activin Receptors↗

Effects of neocarzinostatin-chimeric Fab conjugates on the growth of human pancreatic carcinoma xenografts.

Neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of MAb A7 (chA7Fab) directed against human pancreatic carcinoma. The anti-tumour effect of chA7Fab-NCS was tested in a nude mouse model on pancreatic carcinoma and compared with A7-NCS or NCS alone. The anti-tumour effect of chA7Fab-NCS increased in a dose-dependent manner and was significantly greater than either A7-NCS or NCS. Tumour growth was completely suppressed after the administration of chA7Fab-NCS. An enzyme-linked immunosorbent assay with rabbit anti-mouse immunoglobulin was performed to examine the antigenicity of chA7Fab. ChA7Fab had less reactivity with rabbit anti-mouse immunoglobulin than either whole antibody A7 or murine Fab fragments of A7. Thus, chA7Fab-NCS can inhibit human pancreatic cancer growth in an animal and may be useful for targeting chemotherapy to pancreatic cancer in humans.

Animals↗

Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients.

AIM: The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated. METHOD: The study group was composed of 68 patients with gastric ulcers and 51 with duodenal ulcers, all were H. pylori-positive. The participants were assigned at random to the lansoprazole alone group (lansoprazole 30 mg o.m. for 6 or 8 weeks) or the lansoprazole plus amoxycillin group (lansoprazole alone regimen plus amoxycillin at 500 mg q.d.s. concomitantly for the first 2 weeks). Healed patients were not given maintenance treatment with acid secretion inhibitors. The cure rate for H. pylori infection and the ulcer recurrence rate after 1 year were investigated. RESULT: The cure rate for H. pylori infection was 4.2% in patients receiving lansoprazole alone and 38.5% in patients receiving lansoprazole plus amoxycillin (P < 0.01) for gastric ulcers, and 0% in patients receiving lansoprazole alone and 61.9% in patients receiving lansoprazole plus amoxycillin (P < 0.001) for duodenal ulcers. The recurrence rate was 42.3% in patients receiving lansoprazole alone and 28.6% in patients receiving lansoprazole plus amoxycillin for gastric ulcers, and 66.7% for patients receiving lansoprazole alone and 11.1% for patients receiving lansoprazole plus amoxycillin (P < 0.001) for duodenal ulcers. None of the patients with gastric or duodenal ulcers cured of H. pylori infection had a recurrence. CONCLUSION: Concomitant use of lansoprazole and amoxycillin increased the curative effects on H. pylori infection. However, the cure rates with this regimen remained inadequate.

2-Pyridinylmethylsulfinylbenzimidazoles↗