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K Obata

Publications and source records attributed to K Obata.

At least 91 records · Page 5Linked to original sources
PubMed1998

Pleomorphic adenoma of the minor salivary gland with pseudoepitheliomatous hyperplasia of the overlying oral mucosa: report of two cases.

Two cases of intra-oral pleomorphic adenoma with marked pseudoepitheliomatous hyperplasia of the overlying oral mucosa are reported. Incisional biopsy specimens, taken a few weeks before surgical excision of the tumor, showed no squamous cell element. Surgically excised specimens revealed pseudoepitheliomatous hyperplasia with hyperortho- and para-keratinization, which extended from overlying oral squamous epithelium, where an incisional biopsy was performed into the deep tumor area. Approximately half of the tumor area in case 1 and one-third in case 2 were occupied by hyperplastic squamous epithelium of the oral mucosa. Although the induction mechanism of such prominent pseudoepitheliomatous hyperplasia of the overlying oral mucosa occupying more than one-third of the tumor area could not be understood, it is thought that surgical injury and/or focal anesthesia during the incisional biopsy played an important role. To the best of our knowledge, these two cases represent the first reported association between benign salivary gland tumor and marked pseudoepitheliomatous hyperplasia of the overlying oral mucosa.

Adenoma, Pleomorphic↗
PubMed1998

Cholesterol-lowering effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on cholesterol diet-fed rats and rabbits.

Pharmacological characterization of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was performed with both in vitro and in vivo assay systems. NTE-122 inhibited microsomal ACAT activities of various tissues (liver of rabbit and rat, small intestine of rabbit and rat, and aorta of rabbit) and cultured cells (HepG2 and CaCo-2), with IC50 values from 1.2 to 9.6 nM. The inhibition mode of NTE-122 was competitive for HepG2 ACAT. NTE-122 had no effect on other lipid metabolizing enzymes, such as 3-hydroxy-3-methylglutaryl-CoA reductase, acyl-CoA synthetase, cholesterol esterase, lecithin:cholesterol acyltransferase, acyl-CoA:sn-glycerol-3-phosphate acyltransferase and cholesterol 7alpha-hydroxylase up to 10 microM. When NTE-122 was administered to the cholesterol diet-fed rats, serum and liver cholesterol levels were markedly reduced with an ED50 of 0.12 and 0.44 mg/kg/day, respectively. In the cholesterol diet-fed rabbits, NTE-122 significantly lowered plasma and liver cholesterol levels at more than 2 mg/kg/day. These results indicate that NTE-122 is a potent, selective and competitive inhibitor of ACAT, making it a worth while therapeutic agent for hypercholesterolemia and atherosclerosis.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed1998

The presenilin 2 loop domain interacts with the mu-calpain C-terminal region.

Presenilin 2 (PS2) is a gene responsible for the early-onset familial Alzheimer's disease (AD). PS2 mutations are considered to be closely related to the pathogenesis of AD. We screened for proteins that interact with PS2 to understand its pathological and physiological functions. Using the PS2 loop domain as the bait, the yeast two-hybrid system was used for screening, and mu-calpain was identified as a PS2 binding protein. In COS-1 cells, the interaction of PS2 with mu-calpain was confirmed by immunoprecipitation. These results suggested that PS2 and mu-calpain interact with each other, and might regulate each other's functions.

Animals↗
PubMed1998

[The significance of determination of urinary type IV collagen concentrations from a random urine collection in patients with non-insulin dependent diabetes mellitus].

Recently, we have developed a highly sensitive assay system for quantitative measurement of urinary type IV collagen. To obtain a basic evaluation of the assay system we used urine specimens, collected randomly and studied the relation to diabetic nephropathy in patients with non-insulin dependent diabetes mellitus (NIDDM). It was shown that this assay system could measure the samples without concentrating the urine. Urinary sediments which were reported to interfere with the assay could be removed by adding Tris-buffer. In the clinical studies, urinary type IV collagen concentrations were significantly higher in patients with NIDDM regardless of the presence or the absence of albumin. Cases with abnormal values of urinary type IV collagen in the normal albuminuria group were 41.6%, while those with abnormal values of urinary transferrin excretion were 31.0%. Furthermore, among the normal albuminuria group, glycosylated hemoglobin (HbA1c) levels were higher in the groups of abnormal values of urinary type IV collagen than those within the reference values. These results obtained herein suggest that urinary type IV collagen could be a useful marker for the early stage of diabetic nephropathy.

Adult↗
PubMed1997

A novel brain gene, norbin, induced by treatment of tetraethylammonium in rat hippocampal slice and accompanied with neurite-outgrowth in neuro 2a cells.

Tetraethylammonium (TEA) induces long-term potentiation (LTP)-like synaptic enhancement in rat hippocampal slices. To find the genes related to this phenomenon, subtraction screening was performed between the mRNA of TEA-treated slices and that of untreated whole brain. One of the clones induced by the TEA treatment, named as norbin, was expressed only in neural tissues. The predicted protein sequence of norbin consisted of 729 amino acids, and no homologies in the sequence were found with known genes or proteins. Overexpression of norbin in cultured Neuro 2a cells by cDNA transfection induced neurite-outgrowth. Since in the course of neural plasticity the formation of new synapses should occur, the neurite-outgrowth-related protein, norbin, might play an important role in neural plasticity.

Amino Acid Sequence↗
PubMed1997

Ultraviolet resonance Raman spectra of Trp-182 and Trp-189 in bacteriorhodopsin: novel information on the structure of Trp-182 and its steric interaction with retinal.

Ultraviolet (244 nm) resonance Raman spectra of Trp-182 and Trp-189 in bacteriorhodopsin were obtained by subtracting the spectrum of the mutants, Trp-182-->Phe or Trp-189-->Phe, from that of the wild-type. Analysis of the spectra shows that the chi2,1 torsion angle about the Cbeta-C3 bond is +/-93 degrees for Trp-182 and +/-100 degrees for Trp-189. Both Trp residues are moderately hydrogen bonded to proton acceptors at their indolyl nitrogens in hydrophobic environments. The environmental hydrophobicity is particularly strong for Trp-182, as judged from the splitting of the W7 Raman band to a triplet. The Raman information on the structure and environment of Trp-189 is consistent with the molecular model from electron diffraction [Grigorieff et al. (1996) J. Mol. Biol. 259, 393-421]. On the other hand, the chi2,1 angle and the hydrogen-bonding state of Trp-182 found here differ from those in the model structure. Revision of the model to correspond to the Raman findings would require a 60 degrees rotation of the Trp-182 indole ring about the Cbeta-C3 bond toward the chromophore retinal and the presence of a water molecule that is hydrogen bonded to the indolyl nitrogen. The triplet feature of the W7 band of Trp-182 is attributable to unusually strong steric repulsion between the indole ring and the 9- and 13-methyl groups of the retinal. Resonance Raman spectra in the visible suggest that this steric conflict destabilizes the 13-cis isomeric state of the retinal.

Bacteriorhodopsins↗
PubMed1997

Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase.

In addition to its role as an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is presumed to be involved in the development and plasticity of the nervous system. GABA is synthesized by glutamic acid decarboxylase (GAD), but the respective roles of its two isoforms (GAD65 and 67) have not been determined. The selective elimination of each GAD isoform by gene targeting is expected to clarify these issues. Recently we have produced GAD65 -/- mice and demonstrated that lack of GAD65 does not change brain GABA contents or animal behavior, except for a slight increase in susceptibility to seizures. Here we report the production of GAD67 -/- mice. These mice were born at the expected frequency but died of severe cleft palate during the first morning after birth. GAD activities and GABA contents were reduced to 20% and 7%, respectively, in the cerebral cortex of the newborn GAD67 -/- mice. Their brain, however, did not show any discernible defects. Previous pharmacological and genetic investigations have suggested the involvement of GABA in palate formation, but this is the first demonstration of a role for GAD67-derived GABA in the development of nonneural tissue.

Aging↗
PubMed1997

Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.

STUDY DESIGN: This study is a unique in vitro study on the effects of hydrostatic pressure on human intervertebral disc metabolism. OBJECTIVE: To investigate the effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. SUMMARY OF BACKGROUND DATA: Mechanical stress and hydrostatic pressures influence proteoglycan and protein synthesis rates in bovine articular cartilage and coccygeal discs. However, the mechanism of matrix synthesis regulation of the intervertebral disc under mechanical stress has not been elucidated. METHODS: Twenty-eight human lumbar intervertebral discs obtained from surgery and from cadavers at autopsy were used. Each tissue fraction was charged with medium in a plastic syringe and placed in a water-filled hydrostatic pressure-control vessel. The hydrostatic pressures applied were 1 (control), 3, and 30 atm (atm = atmospheres) for 2 hours. The proteoglycan and protein synthesis rates were determined by radioisotope incorporation. The production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 were measured by a one-step enzyme immunoassay method using monoclonal antibodies. RESULTS: Three atm pressure stimulated proteoglycan synthesis rates in the nucleus pulposus and inner anulus (n = 14 in each tissue). Compared with the control group, 30 atm pressure significantly inhibited proteoglycan synthesis in the inner anulus (P = 0.011). In the nucleus pulposus, matrix metalloproteinase-3 production was stimulated at a pressure of 30 atm relative to 3 atm (P = 0.014, n = 16 in each tissue). The highest tissue inhibitor of metalloproteinases-1 production showed highest values at 3 atm pressure in the inner anulus (n = 16 in each tissue). CONCLUSION: The results suggest that hydrostatic pressure influences intervertebral disc cell metabolism. A physiologic level of hydrostatic pressure (3 atm) may act as an anabolic factor for stimulation of proteoglycan synthesis and tissue inhibitor of metalloproteinases-1 production. This may be essential for maintaining the matrix of the disc. If the pressure was 30 atm or more or 1 atm or less, a catabolic effect will be predominant, with reduction of proteoglycan synthesis rate and increase of matrix metalloproteinase-3 production. Abnormal hydrostatic pressure, therefore, may accelerate disc degeneration.

Cadaver↗
PubMed1997

The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue.

To gain insights into the significance of presenilins (PS) in the pathogenetic mechanisms of early-onset familial Alzheimer disease (FAD), we expressed cDNAs for wild-type PS2 and PS2 with the Volga German (N141I) mutation in cultured cells and then examined the metabolism of the transfected proteins and their effect on the C-terminal properties of secreted amyloid beta protein (A beta). PS2 was identified as a 50- to 55-kDa protein, which was cleaved to produce N-terminal fragments of 35-40 kDa and C-terminal fragments of 19-23 kDa. The Volga German (N141I) mutation did not cause any significant change in the metabolism of PS2. COS-1 cells doubly transfected with cDNAs for N141I mutant PS2 and human beta-amyloid precursor protein (betaAPP) or a C-terminal fragment thereof, as well as mouse Neuro2a neuroblastoma cells stably transfected with N141I mutant PS2 alone, secreted 1.5- to 10-fold more A beta ending at residues 42 (or 43) [A beta42(43)] compared with those expressing the wild-type PS2. These results strongly suggest that the PS2 mutation (N141I) linked to FAD alters the metabolism of A beta/betaAPP to foster the production of the form of A beta that most readily deposits in amyloid plaques. Thus, mutant PS2 may lead to AD by altering the metabolism of A beta/betaAPP.

Alzheimer Disease↗
PubMed1997

Immunohistochemical studies on matrix metalloproteinase-9 (MMP-9) and type-IV collagen in endometrial carcinoma.

Immunohistochemical staining of MMP-9 and the type-IV collagen was performed on paraffin sections of endometrial carcinoma. Immunostaining in 129 cases of endometrial cancer detected MMP-9 in 19.0% of the cases. MMP-9 positive was shown in 30% of the cases with vessel invasion, and in 12.7% of the cases without vessel invasion (p < 0.05). MMP-9 showed positive in many cases with poor differentiation and lymph node metastasis, but still failed to achieve statistical significance. MMP-9 staining did not correlate with disease outcomes. We can not clarify that MMP-9 is associated with tumor-cell invasion and metastasis. Type-IV collagen deposition at the tumor-stromal border was studied in 58 cases of endometrial carcinoma in which disruptions were seen in varying degrees. The type-IV collagen in the primary lesion decreased as the differentiation decreased. Even in the lymph node metastasis lesions, the type-IV collagen was stained and was almost in agreement with the primary lesions. In the primary lesions, there was no relationship between MMP-9 staining and the type-IV collagen. It was suggested that the type-IV collagen observed in endometrial carcinoma was more concerned with the differentiation of the tumor than with the degradation by MMP-9.

Adenocarcinoma↗
PubMed1997

Delayed signal propagation via CA2 in rat hippocampal slices revealed by optical recording.

Signal propagation from mossy fibers to CA1 neurons was investigated in rat hippocampal slices by a combination of electrical and optical recordings. The slices were prepared by oblique sectioning of the middle part of the hippocampus to preserve fiber connections. The mossy fibers were stimulated to induce population spikes (PSs) and excitatory postsynaptic potentials in the middle part of the CA1 region. Latencies of maximal PSs in CA1 varied widely among slices; they ranged from 7 to 13.5 ms, with two maxima at 9 and 11.5 ms. The fastest PSs probably are evoked by the Schaffer collaterals that connect the CA3 and CA1 regions in the well-known trisynaptic circuit. However, the slower PSs suggest the existence of additional delayed inputs. To determine the source of the delayed input, slices were stained with a voltage-sensitive dye, RH482, and the optical signals relevant to membrane potential changes were detected by a high-resolution optical imaging system. Optical recording of responses to mossy fiber stimulation indicated two distinct types of signal propagation from CA3 to CA1. In preparations evincing the fast type of propagation, signals spread to CA1 within 7.2 ms after the mossy fiber stimulation. During such propagation, activity flowed directly from CA3 to the stratum radiatum of CA1. Other preparations illustrated slow signal propagation, in which optical signals were generated in CA2 before spreading to CA1. During such slow signal transmission, activity persisted in CA2 and its surrounding area for 3 ms before propagating to the strata radiatum and oriens in CA1. In such cases, CA1 activity was detected within 10.8 ms of mossy fiber stimulation. In some slices, a mixture of the fast and slow propagation patterns was observed, indicating that these two transmission modes can coexist. Our data reveal that CA2 neurons can transmit delayed excitatory signals to CA1 neurons. We therefore conclude that consideration of electrical signal propagation through the hippocampus should include flow through the CA2 region in addition to the traditional dentate gyrus-CA3-CA1 trisynaptic circuit.

Animals↗
PubMed1997

Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis.

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.

Adult↗
PubMed1997

[Levels of matrix metalloproteinase-3 and urokinase-type plasminogen activator in knee synovial fluids from patients with rheumatoid arthritis and osteoarthritis].

The objective of this study is to determine the levels of matrix metalloproteinase-3 (MMP-3) and urokinase-type plasminogen activator (uPA) in knee synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Knee synovial fluids were collected from patients with RA and OA. Concentrations of MMP-3 were determined by enzyme immunoassay using a pair of monoclonal antibodies against human proMMP-3, and activities of uPA were measured by immunocapture assay using a polyclonal antiserum against human uPA. The median concentration of MMP-3 in synovial fluids was 97.5 +/- 82.6 micrograms/ml (range 1.06-336 micrograms/ml) for RA group and 20.5 +/- 11.3 micrograms/ml (range 6.19-42.8 micrograms/ml) for OA group. Levels of MMP-3 were significantly higher in RA group than in OA group. The median activity of uPA in synovial fluids was 0.053 +/- 0.052 i.u./ml (range 0.003-0.187 i.u./ml) for RA group and 0.072 +/- 0.059 i.u./ml (range 0.006-0.169 i.u./ml) for OA group. No significant difference of uPA activity was observed between RA and OA group. Significant correlation of the levels of MMP-3 with those of uPA was observed in RA group, however not in OA group. The increased levels of MMP-3 in synovial fluids in RA group may reflect an elevated matrix degrading activity due to joint inflammation. The significant correlation of MMP-3 with uPA in RA group suggests that MMP-3 could degrade cartilage matrix more actively in conjunction with PA-plasmin system than MMP-3 alone.

Aged↗
PubMed1997

[Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker for urothelial cancer--NMP22 as a urinary marker for surveillance of bladder cancer. NMP22 Study Group].

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the surveillance of bladder cancer, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 144 patients with histologically diagnosed bladder cancer, 65 patients with other urological cancers, and 171 healthy volunteers by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All bladder cancer patients were evaluated for urinary NMP22 values and voided urine cytology simultaneously from the same urine samples. Based on the data from the bladder cancer patients and the healthy volunteers, the cut-off value was set at 12 U/ml. The median urinary NMP22 value for the bladder cancer patients was 17.8 U/ml (95% CI: 13.1-29.0). The sensitivities of urinary NMP22 and voided urine cytology were 61.1% (88/144) and 33.8% (48/144), respectively, a significant difference (p < 0.00001). Multivariate analysis revealed that tumor size affected the urinary NMP22 values. The positive rate by tumor size was 42.3%, 59.1%, and 85.0% for tumors of < 10 mm, 10-30 mm, and > 30 mm, respectively. Urinary NMP22 values decreased postoperatively in 82.9% of the patients. The median NMP22 values for prostate cancer and renal cancer were 4.4 U/ml (95% CI: 2.2-6.7) and 6.2 U/ml (95% CI: 3.6-12.5). The positive rates were 24.2% and 31.3%, respectively, both of which were significantly lower than for bladder cancer. Our multicenter study indicates that urinary NMP22 test is more sensitive than voided urine cytology test for the surveillance of bladder cancer.

Adult↗
PubMed1997

[Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker for urothelial cancer--screening for urothelial cancer in patients with microscopic hematuria. NMP Study Group].

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 183 patients with microscopic hematuria by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All patients were entered in this study before cystoscopy was performed, and were evaluated for NMP22 values and voided urine cytology simultaneously from the same urine samples. Of the 183 patients with microscopic hematuria, 14 cases of urothelial cancer were detected. For the other cases, 65 were of benign diseases and 104 were designated NED (No Evidence of Disease). The median NMP22 values for urothelial cancer, benign diseases, and NED were 26.5 U/ml (95% CI: 18.5-228.2; 4.9 U/ml (95% CI: 3.6-8.3), and 5.9 U/ml (95% CI: 4.8-6.5), respectively. The urinary NMP22 value for urothelial cancer was significantly higher than for benign diseases and NED. When the cut-off value of urinary NMP22 was set at 12 U/ml, the positive rate of NMP22 for urothelial cancer was 85.7%, significantly higher than the 50% positive rate by voided urine cytology. This study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Adult↗
PubMed1997

Suppression of matrix metalloproteinase-3 synthesis by interleukin-4 in human articular chondrocytes.

OBJECTIVE: To evaluate the effect of interleukin-4 (IL-4) on IL-1 induced matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) production by human articular chondrocytes. METHODS: Monolayer cell culture of chondrocytes was obtained from human articular cartilage from patella within 24 h after death. MMP-3 and TIMP-1 protein levels were determined by ELISA. MMP-3 activity was assayed as caseinase activity. Amounts of MMP-3 and TIMP-1 mRNA were measured by Northern blot analysis. RESULTS: IL-4 suppressed IL-1 stimulated MMP-3 protein and enzyme activity. Moreover, IL-4 suppressed IL-1 induced MMP-3 mRNA. In contrast, IL-4 did not alter the level of TIMP-1 protein and mRNA. CONCLUSION: IL-4 may be implicated as a protective mediator of joint destruction seen in inflammatory arthritis.

Adult↗