Inverse-dynamics representation of eye movements by cerebellar Purkinje cell activity during short-latency ocular-following responses.
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Action Potentials↗
Biomedical subjects
K Kawano
Publications and source records attributed to K Kawano.
Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex.
Five different target mitochondrial autoantigens recognized by sera from patients with primary biliary cirrhosis (PBC) have been identified as subunits of the following 2-oxo acid dehydrogenase complexes: the pyruvate dehydrogenase complex (PDC), the branched chain 2-oxo acid dehydrogenase complex (BCOADC), and the 2-oxoglutarate dehydrogenase complex (OGDC). Unlike the E2 subunits of PDC (PDC-E2) and BCOADC (BCOADC-E2), the E2 subunits of OGDC (OGDC-E2) reactivity of PBC sera and the reactive epitope of OGDC-D2 have not hitherto been studied in detail. In this report, we took advantage of a recombinant fusion protein for OGDC-E2 to address these issues. Eighty of 268 (29.9%) PBC patient sera but none of the 45 controls reacted with recombinant OGDC-E2. The recombinant OGDC-E2 was judged to express the immunodominant epitope, because when sera from patients with PBC were preabsorbed with the recombinant fusion protein, such sera were depleted of reactivity against 48 kD OGDC-E2 when probed on beef heart mitochondria (BHM) but retained reactivity toward PDC-E2 and/or BCOADC-E2. Furthermore, affinity-purified PBC sera against recombinant OGDC-E2 reacted only with native OGDC-E2 and not with any other enzyme components of the 2-oxo acid dehydrogenase complex. Antimitochondrial autoantibodies (AMA) against OGDC-E2 included immunoglobulin (Ig)G2, IgG3 and IgM and the relative titers were as follows: IgG2 > IgG3 > IgM. Finally, using overlapping recombinant polypeptides, it was determined that a minimum of 81 amino acids (residues 67-147) corresponding to the lipoyl domain of OGDC-E2 are necessary for reactivity, suggesting that a conformational autoepitope is recognized by AMA. These data suggest that each of the 2-oxo acid dehydrogenase enzymes has distinct antigenicity despite their similarities in structure and function. The availability of recombinant OGDC-E2 autoantigen will allow the design of additional studies to further our understanding of the role of mitochondrial autoantigens in the pathogenesis of PBC.
Animals↗
Implantation of human colorectal carcinoma cells in the liver studied by in vivo fluorescence videomicroscopy.
In vivo fluorescence videomicroscopy (IVFM) was used to analyse the behavior of weakly and highly metastatic human colorectal carcinoma (CRC) cells during implantation in the liver. A highly metastatic human CRC cell line, CX-1, and a weakly metastatic line, Clone A, were double-labeled with rhodamine B isothiocyanate-dextran (Rd-Dx) to locate cells and with calcein AM to assess cell metabolic activity in an experimental metastasis model. Double-labeled CRC cells (2.0 x 10(6)) were injected into the spleens of groups of nude mice and the livers observed by IVFM over the next 72 h. CRC cells were implanted within 30 s after injection into either portal venules or the proximal third of hepatic sinusoids. Approximately 0.5% of CRC cells traversed the liver through portal-central venous shunts and implanted in the lung. The number of CX-1 cells in the liver was similar to that of Clone A cells during the first 12 h. However, more CX-1 cells than Clone A cells remained in the liver at 4 h and were in groups of 8-12 cells whereas only a few, single Clone A cells were detected in the liver at 72 h. Not all Clone A cells are committed to die within 4 h of implantation because cells harvested 4 h after hepatic implantation proliferated normally in vitro when removed from the hepatic microenvironment. Since the stress of mechanical deformation during implantation may cause differences in cell survival, CX-1 and Clone A cells were passed through filters with 8 microM pores in vitro at 10-15 cm of water pressure to recreate the trauma of hepatic implantation. Approximately 50% of both CX-1 and Clone A cells were lysed. Furthermore, both CRC lines remained metabolically active when co-cultivated with liver cells for at least 24 h in vitro. Thus, the difference in metastatic potential between the two CRC lines may reside in their response to the combination of mechanical implantation and subsequent growth in the liver parenchyma.
Animals↗
Relationships between diet control and the development of spontaneous type II diabetes and diabetic nephropathy in OLETF rats.
The effect of a 30% restricted diet on the development of diabetes and diabetic nephropathy was examined using the Otsuka Long Evans Tokushima Fatty (OLETF) rat which develops non-insulin-dependent diabetes mellitus (NIDDM) spontaneously after 25-30 weeks of age. The first experimental group that received 30% restricted feeding from six to 80 weeks old, showed complete suppression of spontaneous diabetes up to 40 weeks of age and showed milder histopathological change of pancreatic islets, that those of the control group. The second group which received 30% restricted feeding during 30-80 weeks, showed a gradual decrease in clinical diabetes with age, even though they had already developed diabetes at 25 weeks. In both groups, levels of urinary protein content appeared to decrease, compared with that in control rats, although a gradual increase of urinary protein was observed with age. Histopathologically, glomerular damages were slight to mild in both groups. However, no improvement in nephrotic complication was observed for the group which received a 30% restricted feeding after 70 weeks of age. These results clearly show that the balanced-control diet, given at a 30% restricted feeding level and at an early phase, is effective in the prevention or improvement of NIDDM and nephrotic complications. Diet therapy after 70 weeks of age, however, had little or no effect.
Age Factors↗
Visual inputs to cerebellar ventral paraflocculus during ocular following responses.
The activity of cerebellar Purkinje cells was recorded in the ventral paraflocculus (VPFL) of alert monkeys during ocular following responses induced by brief movements of the visual scene. The mossy fiber input evoked 'simple-spikes' which increased their activity during either ipsiversive or downward motion of the visual scene. On the other hand, the 'complex-spikes' evoked by the climbing fiber input increased their activity during either contraversive or upward movement. To further define the sources of the visual input to the VPFL, we recorded single units in the dorsolateral pontine nucleus (DLPN), which is known to project to the VPFL as mossy fibers, and in the pretectal nucleus of the optic tract (NOT), which is known to project to the inferior olive whose neurons project to the cerebellum as climbing fibers. In both areas, most neurons were directionally selective, and responded to the moving visual scene with very short latencies (approximately 40-60 ms). These results suggest that both DLPN and NOT neurons deliver information concerning movements of the visual scene to the VPFL through different pathways.
Animals↗
MHC class II restriction for T cell proliferative response to mite antigen.
BACKGROUND: We investigated the immunoreguratory role of the major histocompatibility complex in peripheral blood lymphocytes' proliferative response to mite antigen. METHOD: Peripheral blood lymphocytes of Japanese asthmatic patients were incubated with antigen obtained from Dermatophagoides pteronyssinus with a molecular weight of about 15,000, with and without 0.05 microgram/mL of monoclonal antibody against HLA class I or class II for seven days at 37 degrees C humidified in 5% CO2 and 95% air. RESULTS: High and low responders to the mite body antigen were found among the patients while there were no high responders among the healthy individuals tested. In the mite-sensitive asthmatic patients, CD4+ T cells were the population that responded to the antigen. Depletion of CD8+ T cells from the peripheral blood lymphocytes of mite-insensitive individuals caused high responsiveness to the antigen, indicative that the mite-specific CD4+ T cells controlled the high responsiveness and the antigen-specific CD8+ T cells, the low responsiveness. Anti-HLA-DR monoclonal antibody inhibited responsiveness. In contrast, anti-HLA-DQ monoclonal antibody produced high responsiveness in low responders to mite antigen. CONCLUSION: High T cell proliferative responsiveness to mite antigen was restricted by HLA-DR antigen through CD4+ T cells in high responders, whereas HLA-DQ antigen is a restriction antigen of low responsiveness through CD8+ T cells in low responders and non-atopic individuals.
Animals↗
Chymotrypsin inhibition induced by side chain-side chain intramolecular CH/pi interaction in D-Thr-L-Phe benzylamide.
The dipeptide benzyl amide H-D-Thr-Phe-NH-CH2-C6H5 was found to inhibit chymotrypsin strongly (K1 = 4.5 x 10(-6) M) in a competitive manner. When a series of phenyl amides H-D-Thr-Phe-NH-(CH2)n-C6H5 (n = 0-4) were tested, inhibitory potency peaked at n = 1 (benzyl amide). Incorporation of a methyl group into the benzyl methylene resulted in formation of stereoisomers, H-D-Thr-Phe-NH-(R or S)-CH(CH3)-C6H5, with considerably different inhibitory potencies. The R-isomer was as active as the benzyl amide, while the S-isomer was about 30-fold less active than the benzyl amide. Furthermore, when a fluorine atom was introduced into the para-position of the amide-benzyl group, the resulting H-D-Thr-Phe-NH-CH2-C6H4(p-F) showed considerably enhanced inhibitory activity (about 5-fold, K1 = 9.1 x 10(-7) M). In conformational analysis by 400 mHz 1H-NMR, all dipeptides having D-Thr-Phe backbone structure showed large upfield shifts of D-Thr-beta OH (shifts in ppm, 0.09-0.17), D-Thr-beta CH (0.23-0.32), and D-Thr-gamma CH3 (0.38-0.53), indicating the presence of shielding effects from the benzene ring. In addition, NOE enhancements between the D-Thr-gamma CH3 and Phe-phenyl groups were evidenced by measurements of two-dimensional NOESY spectra and NOE difference spectra. These observations demonstrated the spatial proximity of these side chains, which is due to side chain-side chain CH/pi interaction. All these results support the idea that the amide-benzyl group binds at the chymotrypsin S1 site, while the hydrophobic core with CH/pi interaction binds at the S2 or S1' site.
Chymotrypsin↗
Purification, characterization, and sequencing of two cysteine proteinase inhibitors, Sca and Scb, from sunflower (Helianthus annuus) seeds.
Two proteinaceous cysteine proteinase inhibitors (cystatins) referred to as Sca and Scb were purified to homogeneity from the seeds of sunflower (Heliantas annuus) by gel filtration on Sephadex G-75 followed by a series of ion-exchange column chromatographies and reverse-phase HPLC (RP-HPLC). The isoelectric points (pI) of Sca and Scb were estimated to be 5.6 and 9.6, respectively. The inhibitory potencies of these two cystatins were examined with cysteine proteinases from various sources, such as plants, mammals, and bacteria. Papain was strongly inhibited by both Sca and Scb with Ki values of 5.6 x 10(-9) and 1.7 x 10(-10) M, respectively. Sca and Scb were also found to be potent inhibitors of ficin (Ki values of 1.9 x 10(-6) and 2.8 x 10(-9) M, respectively). Rat cathepsin H was inhibited strongly by Scb and slightly by Sca. Although rat cathepsins B and L were significantly inhibited by Scb, they were scarcely affected by Sca. Neither Sca nor Scb inhibited Arg-gingipain, an arginine-specific cysteine proteinase of Porphyromonas gingivalis. The complete amino acid sequences of the two inhibitors were determined by protein chemical methods. The proteins Sca and Scb consist of 83 and 101 amino acid residues with M(r) of 9,330 and 11,187, respectively, and there are identical residues at 34 positions in the two sequences, that is at 42% of the residues compared. Comparison of their sequences with those of other cystatins revealed that Sca shares 59-73% identical residues with other phytocystatins, while Scb shows less identity to other phytocystatins, sharing only 28-38% identical residues. Furthermore, only 20-27% of the residues of both cystatins, Sca and Scb, are identical to those of the animal cystatins.
Amino Acid Sequence↗
Vertebral growth disturbance in rapidly growing rats during 14 days of spaceflight.
The effect of 14 days of spaceflight on the vertebrae of rapidly growing rats was studied. The hardness of the vertebrae was measured with a Knoop microhardness tester, and bone mineral density was measured from X-ray photographs. Histomorphometric examination was performed with a microcomputer-aided system. No significant difference (P > 0.05) was observed between flight rats and ground controls with regard to mechanical hardness or bone mineral density. However, histological examination revealed irregular thickening of the endosteal surface of cortical bone in the flight rats, whereas it was uniform in the ground controls. The relative area of lamellar bone showed a significant reduction (P < 0.001) in the flight rats. These findings suggest that the structural disturbances were due to retardation of endosteal modeling and remodeling. We conclude that delay of vertebral maturation can occur in rapidly growing rats after even short-term exposure to microgravity.
Animals↗
Dynamic MR imaging of the temporomandibular joint in patients with arthrosis: relationship between contrast enhancement of the posterior disk attachment and joint pain.
OBJECTIVE: The purpose of this study was to determine the relationship between joint pain, disk position, and the degree of contrast enhancement of the posterior disk attachment in patients with temporomandibular joint arthrosis using dynamic contrast-enhanced MR imaging. SUBJECTS AND METHODS: T1- and T2-weighted spin-echo and spoiled gradient-recalled acquisition in the steady state MR imaging was performed in 36 healthy volunteers and 105 patients who were asymptomatic or who had joint pain, muscular pain, or both. On T1-weighted images, the position of the disk was classified as normal and anteriorly displaced. Next, on sagittal spoiled gradient-recalled acquisition in the steady state MR images, signal intensity from teh posterior disk attachment was measured. Time-intensity curves of the signal-intensity ratio versus the time after contrast administration were obtained in each case. Diagnostic accuracy of enhancement among the clinical symptoms was assessed using receiver operating characteristic curves. Imaging findings of contrast enhancement were correlated with pain and disk position. RESULTS: In quantitative measurement, a rapid enhancement pattern was seen most frequently in patients with joint-pain, whereas relatively gradual enhancement was seen in the healthy subjects and in patients who were asymptomatic or who had muscular pain. The mean peak-signal-intensity ratio of the group with joint pain was significantly higher than that of the other groups (p < .001). In the group with joint pain, anterior disk displacement without reduction was strongly associated with the mean signal-intensity ratio (p < .01). With regard to receiver operating characteristic analysis, the group with joint pain showed significantly greater accuracy than did the other groups (p < .001). CONCLUSION: Our results suggest that prominent contrast enhancement of the posterior disk attachment on spoiled gradient-recalled acquisition in the steady state MR images may help differentiate intraarticular from extraarticular causes of pain in and around the temporomandibular joint. In the group with joint pain, anterior disk displacement without reduction was closely associated with prominent enhancement.
Adolescent↗
Primary intramedullary spinal cord germinoma. Case report.
Primary central nervous system germinoma usually presents as an extraaxial intracerebral mass. The authors report the rare occurrence of an intramedullary spinal cord germinoma at the conus medullaris in a 24-year-old man, which was treated by partial removal and radiation therapy. The tumor was highly radiosensitive and the patient remains disease free 15 months posttreatment.
Adult↗
TMC-1 A, B, C and D, new antibiotics of the manumycin group produced by Streptomyces sp. Taxonomy, production, isolation, physico-chemical properties, structure elucidation and biological properties.
Four new antitumor antibiotics, TMC-1 A, B, C and D were isolated from a fermentation broth of Streptomyces sp. A-230. Spectroscopic studies have shown that TMC-1 A to D were new members of the manumycin class of antibiotics. These antibiotics showed cytotoxic activities against various tumor cell lines in vitro.
Animals↗
FK506 reduces oxidative hepatic injury following cold ischemic preservation and transplantation.
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Alanine Transaminase↗
Effects of lipo-prostaglandin E1 on chemokine release in ischemia and reperfusion of the liver.
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Alprostadil↗
[Establishment of reference intervals and physiological parameters for 13 serum proteins in healthy Japanese adults].
Using a nephelometry with a new calibrator in which values were assigned from EU/CRM470, a new international reference preparation, we have established for the first time the reference intervals of 13 different serum proteins in Japanese adults. Based on the NCCLS guideline C28-P, a new statistical and concrete procedure was revised and used for this study. It is clearly shown here that standardisation of serum proteins can be possible under the qualified assay system, making it possible to share the reference intervals among laboratories under well-controlled quality assurance. New aspects of serum protein variations were discovered in relation to physiologic changes and life styles.
Adult↗
[A case of liver metastasis from so-called hepatoid adenocarcinoma of stomach with lipiodol accumulation].
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Adenocarcinoma, Papillary↗
Relationship between oral breathing and nasal obstruction in patients with obstructive sleep apnea.
In 30 normal subjects and 20 patients complaining of snoring or sleep apnea nasal percentage of total respiratory air volume (nasal fraction) was measured when nasal resistance was gradually increased. The switching point from nasal to oral breathing was also examined. Nasal respiratory resistance was measured by a rhinograph, and nasal fraction was measured with an inductive body-plethysmograph and with a CPAP nasal mask when the patients were at rest. Several sizes of cotton pledgets were inserted into the nasal vestibules as obturators, and nasal respiratory resistance and nasal fraction were measured repeatedly until subjects had to breathe through the mouth completely. Although the value of nasal respiratory resistance in patients with complaints of snoring or sleep apnea was higher than that of normal subjects, most of the patients did not complain of a sensation of nasal obstruction. However, the switching point from nasal to oro-nasal breathing in patients with complaints of snoring or sleep apnea was statistically higher than that in normal subjects. These results suggest that patients with complaints of snoring or sleep apnea can easily breathe through the mouth during sleep, and that chronic nasal obstruction may induce obstructive sleep apnea. Therefore, measurements of nasal respiratory resistance and nasal fraction are useful to evaluate obstructive sleep apnea.
Humans↗
Changes in nasal and oral respiratory resistance before and after uvulopalatopharyngoplasty.
Twelve patients with complaints of sleep apnea were examined with the all-night sleep test. They underwent uvulopalatopharyngoplasty (UPPP) and were studied with the all-night sleep test again 3 to 6 months after the operation. Nasal and oral respiratory resistance was measured in sitting and supine position before and after surgery using a microrhinograph. The physiological effect of UPPP was also compared with the results of an MRI anatomical study. Nasal and oral respiratory resistance was significantly decreased post-operatively (p <0.05). The decreased value of post-operative nasal respiratory resistance in a supine position was more marked than that of oral resistance, suggesting that UPPP eliminates the obstruction at the soft palate, especially in a supine position. Although our study was performed in awake patients enlargement of the airway in the middle pharyngeal region may improve the nasal and oral respiratory function during sleep.
Airway Obstruction↗